R/progGUIP1.R
In ddinart/GUIP1: Graphical User Interface for Phase I Designs
Defines functions
.CRMB
.CRML
.TITECRM
.EWOC
.TEWOC
.titeewoc
.titeewocsim
.print.titeewoc
.print.titeewoc.sim
.plot.titeewoc
GUIP1
Documented in
GUIP1
.CRMB=function(pos=1, e)
{
e$CRM.2 = NULL
e$ResSim = NULL
tclRequire("Tktable")
remplireRequid=function()
{
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
Model=as.numeric(tclvalue((rbValue.M)))
if (Model==1){Model.n="logistic"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (Model==2){Model.n="empiric"; intcpt=NULL}
Stop=as.numeric(tclvalue(rbValue.SC))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
assign("names_Study", tclvalue(tkget(names.S)), envir = as.environment(pos))
assign("Study",list(name=paste(names_Study) ,Nb_Dl=Nb_Dl, DL=DL, Target=Target, Model=Model, Model.n=Model.n,
Stop=Stop, N_Pat=N_Pat ,N_pat_Level=N_pat_Level, halfwidthPrior=halfwidthPrior,
nuPrior=nuPrior, Intcpt=intcptPrior, Sd=sdPrior), envir = as.environment(pos))
differ=abs(Study$DL-Study$Target)
MTD=1
for ( i in 1 : Study$Nb_Dl)
{
if (differ[i]==min(differ))
{MTD=i}
}
Pat_include=0
PT.data=NULL
assign("Res",list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data), envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
assign("a00", paste(names_Study), envir = as.environment(pos))
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'crmb', sep='.'))
}
Study.file()
tk2notetab.select(net.CRMB , "Include")
}
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
tk2notetab.select(net.CRMB , "Input parameters")
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses<- nlevel
priorProbaf <- c()
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (tkget(eval(parse(text = paste('valp',i,sep='')))))
priorProbaf <- c(priorProbaf,as.numeric(tclvalue(n.iter)))
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter, state="disabled"),envir = as.environment(pos)),sticky="w",row=r,column=1)
}
if (any(priorProbaf <= 0) | any(priorProbaf >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(priorProbaf, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
SliderValue=tclVar(nlevel)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue,state="disabled",
resolution=1, orient="horiz")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(TargetPrior)
Target<-tkentry(Saisi, width=5,textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi) ; rb2.1 <- tkradiobutton(Saisi)
rbValue.M <- tclVar(modelPrior)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic", state="disabled", font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric", state="disabled", font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(sdPrior)
sd.<-tkentry(Saisi,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=8,column=0, sticky="w")
tkgrid(sd., row=8,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(intcptPrior)
}else {tclVar("NA")}
assign("intcpt.",tkentry(Saisi, textvariable=n.iter, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=8,column=2, sticky="w")
tkgrid(intcpt., row=8,column=3, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam<- tclVar()
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
assign("etatPrior",TRUE,envir = as.environment(pos))
}
disabled.PriorCalib=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
if(is.tkwin(SaisiCal)){tkdestroy(SaisiCal)}
if(is.tkwin(Saisi.saveCal )){tkdestroy(Saisi.saveCal )}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar(Study$Nb_Dl)
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
for ( i in 1:Study$Nb_Dl)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar (tkget(eval(parse(text = paste('val',i,sep='')))))
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCAL,text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCAL,state="disabled", width=8,textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
if(Study$Nb_Dl!=8)
{
for ( i in (Study$Nb_Dl+1):8)
{
r=10 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
n.iter=tclVar(round(TargetPrior,3))
Target.cal<-tkentry(SaisiCal,textvariable=n.iter,state="disabled", width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
n.iter=tclVar(halfwidthPrior)
halfwidth<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal,state="disabled") ; rb2.1CAL <- tkradiobutton(SaisiCal,state="disabled")
assign("rbValue.MCAL", tclVar(modelPrior), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
n.iter=tclVar(nuPrior)
nu<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_nu, row=6,column=0, sticky="w")
tkgrid(nu, row=6,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
n.iter=tclVar(Study$Sd)
sd.<-tkentry(SaisiCal,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=7,column=0, sticky="w")
tkgrid(sd., row=7,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(Study$Intcpt)}
else {tclVar("NA")}
assign("intcpt.", tkentry(SaisiCal, textvariable=n.iter, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,bg="cornflower blue",state="disabled")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,bg="cornflower blue",state="disabled")
tkgrid(Validation, row=2)
}
PriorCalib=function(...)
{
.Crea.f.CAL=function(...)
{
assign("TargetPrior", as.numeric(tclvalue(tkget((Target.cal)))), envir = as.environment(pos))
assign("halfwidthPrior", as.numeric(tclvalue(tkget((halfwidth)))), envir = as.environment(pos))
assign("nuPrior", as.numeric(tclvalue(tkget(nu))), envir = as.environment(pos))
assign("nlevel", as.numeric(tclvalue(tkget((slider_Nb_DL.CAL)))), envir = as.environment(pos))
assign("modelPrior", as.numeric(tclvalue(((rbValue.MCAL)))), envir = as.environment(pos))
assign("sdPrior", as.numeric(tclvalue(tkget((sd.)))), envir = as.environment(pos))
assign("intcptPrior", as.numeric(tclvalue(tkget((intcpt.)))), envir = as.environment(pos))
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
if (TargetPrior>0.55) cat("\n Warning: Target DLT rate too high")
if (TargetPrior<0.15) cat("\n Warning: Target DLT rate too low")
if ((halfwidthPrior<=0)|(halfwidthPrior>0.5)) stop('Halfwidth of the indifference intervals incorrect!')
if ((halfwidthPrior<=0.5)&(halfwidthPrior>0.2)) cat("\n Warning: Try to reduce the value of the halfwidth of the indifference intervals ")
if ((nuPrior<1)|(nuPrior>Nb_Niv_DosesCAL)|(nuPrior%%1 != 0)) stop(paste('Prior guess of MTD incorrect, enter an integer between 1 and',Nb_Niv_DosesCAL))
if (modelPrior==1)
{
e$prior<-dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel, model="logistic", intcpt=intcptPrior)
}
if (modelPrior==2)
{
e$prior<-dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel, model="empiric")
}
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(round(e$prior[i],3))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,textvariable=n.iter),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_DosesCAL!=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
f.CALPrior=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("affCAL",tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8), envir = as.environment(pos)),row=r,column=1)
}
if(Nb_Niv_DosesCAL !=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Param.choice = function(...)
{
if (as.numeric(tclvalue((rbValue.MCAL)))==2)
{
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(SaisiCal, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar('8')
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",command=f.CALPrior)
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
Target.cal<-tkentry(SaisiCal, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
halfwidth<-tkentry(SaisiCal, width=10)
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
rb2.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
rbValue.MCAL <- tclVar(1)
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
sd.<-tkentry(SaisiCal, width=10)
tkgrid(Tsd., row=4,column=2, sticky="w")
tkgrid(sd., row=4,column=3, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
nu<-tkentry(SaisiCal, width=10)
tkgrid(lab_nu, row=7,column=0, sticky="w")
tkgrid(nu, row=7,column=1, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,command=.Crea.f.CAL,bg="cornflower blue")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,command=remplireRequid,bg="cornflower blue")
tkgrid(Validation, row=2)
}
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.crmb or file.cbsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
if (extension == "crmb") {
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$CRM.2 <- CRM.2
Open.CRM()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
}
}
if (extension == "bsim") {
load(file =paste(paste(names_Study,'cbsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS",StudyS, envir = as.environment(pos))
tkdestroy(Win_CRMB)
frameInitSIM()
disabled.SimCRM()
}
}
pending_listing=function()
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
dataa=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(dataa)==0 )
{
msg <- paste("No patient pending",sep="")
tkmessageBox(message=msg)
}
if (nrow(dataa)>=1)
{
assign("tt.pend", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(tt.pend, "+650+400")
assign("tl",tklistbox(tt.pend,height=4,selectmode="single",background="white"), envir = as.environment(pos))
tkgrid(tklabel(tt.pend,text="Select a patient",font=PoliceGenerale))
tkgrid(tl)
numPatP=paste("Patient N'", as.character(dataa$patid),sep="")
for (i in (1:length(numPatP)))
{
tkinsert(tl,"end",numPatP[i])
}
tkselection.set(tl,0)
OK.but <-tkbutton(tt.pend,text=" OK ",command=.include.pending,bg="cornflower blue")
tkgrid(OK.but)
tkfocus(tt.pend)
}
}
.include.pending <- function()
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
data.pinding=Res$PT.data[which(Res$PT.data$pndg==1),]
data.inclus=Res$PT.data[which(Res$PT.data$pndg==0),]
numPatP=as.character(data.pinding$patid)
assign("Choice", as.numeric(numPatP[as.numeric(tkcurselection(tl))+1]), envir = as.environment(pos))
print(Choice)
Inc=tktoplevel()
tkwm.geometry(Inc, "+650+400")
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
assign("Titre", tklabel(Inc.mm1,text="DLT",font=PoliceGenerale), envir = as.environment(pos))
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i))))
}
.Sauv2=function(...)
{
assign("DLT", as.numeric(tclvalue((rbValue.DLT))), envir = as.environment(pos))
Newpat=data.pinding[which(data.pinding$patid==Choice),]
Newpat$DLT=DLT
Newpat$pndg=0
DATA=rbind(data.inclus,Newpat)
e$CRM.2 <- dfcrm::crm( prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1],method = "bayes", conf.level = 0.95,
model = paste(Study$Model.n), scale=Study$Sd, intcpt=Study$Intcpt)
Res$MTD=e$CRM.2$mtd
Res$PT.data[which(Res$PT.data$patid==Choice),]$pndg=0
Res$PT.data[which(Res$PT.data$patid==Choice),]$DLT=DLT
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res",Res, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRMB", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRMB,text="Validate",width=30,command=.Sauv2,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRMB)
tkdestroy (tt.pend)
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-bayesian approach (CRMB) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRMB,text="New patient",width=30,command=.include,bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRMB,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRMB, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_CRMB)
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-bayesian approach (CRMB) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
print('CAS 1')
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRMB,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRMB,text="Pending patient",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.CRMB ,"Results")
print(' Fin CAS 1')
tkgrid(Rec.Win_CRMB, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
if (nrow(DATA)!=0)
{
print('CAS 2')
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRMB,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRMB,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRMB, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
print(' Fin CAS 2')
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2]),
envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for (i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,
total.tox=total.tox, ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="15",background="white")
tkgrid(t.d, row=2, column=0)
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2])
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,
total.tox=total.tox, ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
GrapheResults()
dev.off()
pdf(paste(paste(filef,"2",sep=""),"pdf",sep="."))
curvesIC()
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
setColWidths(wb, sheet2, cols=c(3,4), widths = 14.43)
setColWidths(wb, sheet2, cols=c(1,2,5,6,7), widths = 10.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:7,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphics",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Patient history",width=20,command=Export.Graph,bg="cornflower blue")
button3b=tkbutton(Resultas ,text="Dose-tox curves",width=20,command=Export.CurvesIC,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(button3b, row=5, column=3)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.include=function(...)
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
Inc<-tktoplevel()
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for ( i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
tkgrid(assign(paste('rDLT',2,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=2, text=paste("pending"))))
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))), envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))), envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1), envir = as.environment(pos))
assign("pndg", as.numeric (c(Res$PT.data[,4],as.numeric(tclvalue((rbValue.DLT)))==2)), envir = as.environment(pos))
Res$PT.data <- data.frame(DL=DL,DLT=DLT,patid=patid,pndg=pndg)
Res$Pat.included <- Res$Pat.included+1
print(Res$PT.data)
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
print(length(DATA)!=0)
if (nrow(DATA)!=0)
{
e$CRM.2<-dfcrm::crm(prior=Study$DL, target=Study$Target, tox=DATA[,2], level=DATA[,1], method = "bayes", conf.level = 0.95,
model = paste(Study$Model.n), scale=Study$Sd, intcpt=Study$Intcpt)
Res$MTD <- e$CRM.2$mtd
}
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRMB", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRMB,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRMB)
}
GrapheResults=function(...)
{
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
n=length(DATA[,1])
x=c(1:n)
y=DATA[,1]
z=DATA[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
Export.Graph=function()
{
GrapheResults()
}
curvesIC = function(...)
{
post.var <- e$CRM.2$post.var
crit <- qnorm(0.5 + e$CRM.2$conf.level/2)
doses=e$CRM.2$dosescaled
Fempi=function(doses,beta){doses^(exp(beta))}
Flogi=function(doses,beta){(1 + exp(-e$CRM.2$intcpt- exp(beta) * doses))^{-1}}
Fmodel <- switch(e$CRM.2$model,empiric=Fempi, logistic=Flogi)
plot(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),'l', lwd=2,xaxt="n",
ylim=c(0, 1),xlab="Dose level", ylab="Proba. of DLT")
axis(1, at = seq(1, length(e$CRM.2$prior), by = 1))
abline(h=e$CRM.2$target,col="blue",lty=2,lwd=2)
objtitle <-rbind("Dose-toxicity curve + 0.95_IC",paste(e$CRM.2$model, "model"))
title(main=objtitle)
legend('topright',c("Proba. of DLT", "IC(0.95)","target"),lty=c(1,1,2), col=c('black','red','blue'),lwd=2)
points(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),lwd=2)
if (post.var >= 0) {
lb <- e$CRM.2$estimate - crit * sqrt(post.var)
ub <- e$CRM.2$estimate + crit * sqrt(post.var)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,lb),col="red",lwd=2)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,ub),col="red",lwd=2)
}else{print('Confidence interval not calculated')}
}
Export.CurvesIC=function()
{
curvesIC()
}
NewCRM=function()
{
tkdestroy(Win_CRMB)
frameInitCRM()
PriorCalib()
}
disabled.CRM=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.CRM=function()
{
tkdestroy(Win_CRMB)
frameInitCRM()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=5, textvariable=n.iter,state="disabled"),) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(Study$Sd)
sd.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tsd., row=6,column=2, sticky="w")
tkgrid(sd., row=6,column=3, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
n.iter <- tclVar(Study$Intcpt)
intcpt.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
Titre=tklabel(Saisi,text="Names of study",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(Titre, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
WordExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
docx( ) %>%
addFlexTable(dframe %>%
FlexTable(header.cell.props = cellProperties( background.color = "#003366"),
header.text.props = textBold(color = "white"),
add.rownames = TRUE ) %>%
setZebraStyle(odd = "#DDDDDD", even = "#FFFFFF")) %>%
writeDoc(file = "ResExport.docx")
Save.word.infos <- tkmessageBox(title = "Word Export",
message = "File ResExport.docx saved in the current working directory of the R proces", icon = "info", type = "ok")
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00<-paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'cbsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'cbsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("bayesian approach (CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
disabled.SimCRM=function()
{
.RecapSimB=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00<-paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'cbsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'cbsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("bayesian approach (CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,command=function()ExcellExport(ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
Nb_Niv_Doses<- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
n_<-tkentry(Saisi_, width=5, textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,state="disabled") ; rb2.1_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Model == "logistic") {
rbValue.M_ <- tclVar(1)
n.intcpt <- tclVar(StudyS$Intcpt)}
if (StudyS$Model == "empiric") {
rbValue.M_ <- tclVar(2)
n.intcpt <- tclVar("NA")}
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation", font=PoliceGenerale)
n.iter <- tclVar(StudyS$Sd)
sd_<-tkentry(Saisi_, width=7, textvariable=n.iter, state="disabled")
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
intcpt_<-tkentry(Saisi_, width=7, textvariable=n.intcpt, state="disabled")
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ;
const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimCRM=function()
{
tkdestroy(Win_CRMB)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Param.c_ = function(...)
{
if (as.numeric(tclvalue((rbValue.M_)))==2)
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=7, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_",tkentry(Saisi_, width=7),envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
seed=1;target=NULL;Model=NULL
npat=NULL;nsim=1;x0=1
target=as.numeric(tclvalue(tkget((Target_))))
Model=as.numeric(tclvalue((rbValue.M_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
npat=as.numeric(tclvalue(tkget(n_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
seed=as.numeric(tclvalue(tkget((Seed_))))
sdv=as.numeric(tclvalue(tkget((sd_))))
if (Model == 1) {model=as.character("logistic");intcp=as.numeric(tclvalue(tkget(intcpt_)))}
if (Model == 2) {model=as.character("empiric");intcp=NULL}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("Names_Study", tclvalue(tkget(names.S_)), envir = as.environment(pos))
assign("StudyS",list(Name=paste(Names_Study),Nb_Dl=Nb_Dl,True=true,Prior=prior,Target=target,
Model=model,Npat=npat,Nsim=nsim,X0=x0, Intcpt=intcp, Sd=sdv,
Constrain=Const, Seed=seed), envir = as.environment(pos))
if (res.users == 1) {
cat("\n Submission in progress... Please wait... ")
e$ResSim <- dfcrm::crmsim(PI=StudyS$True, prior=StudyS$Prior,target=StudyS$Target,n=StudyS$Npat,
x0=StudyS$X0,nsim=StudyS$Nsim,method="bayes",model=StudyS$Model,count=FALSE,
intcpt=StudyS$Intcpt, scale=StudyS$Sd, restrict=StudyS$Constrain, seed=StudyS$Seed)
.RecapSim()
tk2notetab.select(net.CRMB_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
Target_<-tkentry(Saisi_, width=5)
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n_<-tkentry(Saisi_, width=5)
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_, command=.Param.c_) ; rb2.1_ <- tkradiobutton(Saisi_, command=.Param.c_)
rbValue.M_ <- tclVar(1)
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation",font=PoliceGenerale)
sd_<-tkentry(Saisi_, width=7)
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_",tkentry(Saisi_, width=7),envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=18)
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive CRM or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Continual Reassessment Method bayesian Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=dfcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRMB", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRMB, "630x472")
tkwm.geometry(Win_CRMB, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRMB, ilogo)
tktitle(Win_CRMB) <- "GUI CRMB"
tkpack.propagate(Win_CRMB, FALSE)
topMenu <- tk2menu(Win_CRMB)
tkconfigure(Win_CRMB, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command= function(){ tkdestroy(Win_CRMB);frameInit()})
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRMB))
}
frameInitCRM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRMB",tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRMB, "680x555")
tkwm.geometry(Win_CRMB, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRMB, ilogo)
tktitle(Win_CRMB) <- "GUI CRMB"
tkpack.propagate(Win_CRMB, FALSE)
topMenu <- tk2menu(Win_CRMB)
tkconfigure(Win_CRMB, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command= function(){ tkdestroy(Win_CRMB);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRMB))
assign("net.CRMB", tk2notebook(Win_CRMB, tabs = c("Prior calibration","Input parameters","Include","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRMB , fill = "both", expand = 1)
assign("Include", tk2notetab(net.CRMB , "Include"), envir = as.environment(pos))
tkpack.propagate(Include, FALSE)
assign("Resultas", tk2notetab(net.CRMB , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.CRMB , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("PriorCal", tk2notetab(net.CRMB , "Prior calibration"), envir = as.environment(pos))
tkpack.propagate(PriorCal, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save" ,tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.Win_CRMB, row=9, column=2, rowspan=16)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL, envir = as.environment(pos))
assign("nuPrior", NULL, envir = as.environment(pos))
assign("etatPrior", FALSE, envir = as.environment(pos))
}
frameInitSIM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRMB",tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRMB, "660x595")
tkwm.geometry(Win_CRMB, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRMB, ilogo)
tktitle(Win_CRMB) <- "GUI CRMB"
tkpack.propagate(Win_CRMB, FALSE)
topMenu <- tk2menu(Win_CRMB)
tkconfigure(Win_CRMB, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command= function(){ tkdestroy(Win_CRMB);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRMB))
assign("net.CRMB_", tk2notebook(Win_CRMB, tabs = c("Input parameters","Results")), envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRMB_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.CRMB_ , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.CRMB_ , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkpack.propagate(m2_, FALSE)
}
frameInit()
}
.CRML=function(pos=1, e)
{
e$CRM.2=NULL
tclRequire("Tktable")
remplireRequid=function()
{
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
Model=as.numeric(tclvalue((rbValue.M)))
if (Model==1){Model.n="logistic"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (Model==2){Model.n="empiric"; intcpt=NULL}
Stop=as.numeric(tclvalue(rbValue.SC))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
assign("names_Study",'', envir = as.environment(pos))
assign("names_Study", tclvalue(tkget(names.S)), envir = as.environment(pos))
assign("Study", list(name=paste(names_Study),Nb_Dl=Nb_Dl,DL=DL,Target=Target,Model=Model,Model.n=Model.n,
Stop=Stop,N_Pat=N_Pat,N_pat_Level=N_pat_Level,halfwidthPrior=halfwidthPrior,
nuPrior=nuPrior, Intcpt=intcptPrior, Sd=sdPrior), envir = as.environment(pos))
differ=abs(Study$DL-Study$Target)
MTD=1
Pat_include=0
PT.data=NULL
assign("Res", list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data), envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(names_Study)
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','CRM',sep=':')
a2='Continual Reassessment Method (CRML) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'crml', sep='.'))
}
Study.file()
tk2notetab.select(net.CRML , "Include")
}
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
tk2notetab.select(net.CRML , "Input parameters")
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses <- nlevel
priorProbaf <- c()
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (tkget(eval(parse(text = paste('valp',i,sep='')))))
priorProbaf <- c(priorProbaf,as.numeric(tclvalue(n.iter)))
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),sticky="w",row=r,column=1)
}
if (any(priorProbaf <= 0) | any(priorProbaf >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(priorProbaf, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
SliderValue=tclVar(nlevel)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1,
state="disabled",orient="horiz")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(TargetPrior)
Target<-tkentry(Saisi, width=5,textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Models",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi) ; rb2.1 <- tkradiobutton(Saisi)
rbValue.M <- tclVar(modelPrior)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic", state="disabled", font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric", state="disabled",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(sdPrior)
sd.<-tkentry(Saisi,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=8,column=0, sticky="w")
tkgrid(sd., row=8,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(intcptPrior)
}else {tclVar("NA")}
intcpt.<-tkentry(Saisi, textvariable=n.iter, width=10, state="disabled")
tkgrid(Tintcpt., row=8,column=2, sticky="w")
tkgrid(intcpt., row=8,column=3, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam<- tclVar()
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
assign("etatPrior", TRUE, envir = as.environment(pos))
}
disabled.PriorCalib=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
if(is.tkwin(SaisiCal)){tkdestroy(SaisiCal)}
if(is.tkwin(Saisi.saveCal )){tkdestroy(Saisi.saveCal )}
assign("affCal.crmb", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCal.crmb, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar(Study$Nb_Dl)
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
for ( i in 1: Study$Nb_Dl)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(tkget(eval(parse(text = paste('val',i,sep='')))))
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCal.crmb,text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCal.crmb,state="disabled", width=8,textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
if(Study$Nb_Dl!=8)
{
for ( i in (Study$Nb_Dl+1):8)
{
r=10 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCal.crmb, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCal.crmb, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
Titre=tklabel(SaisiCal,text="Target DLT rate",font=PoliceGenerale)
n.iter=tclVar(round(TargetPrior,3))
Target.cal<-tkentry(SaisiCal,textvariable=n.iter,state="disabled", width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
n.iter=tclVar(halfwidthPrior)
halfwidth<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_halfwidth, row=3,column=0, sticky="w")
tkgrid(halfwidth, row=3,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal,state="disabled") ; rb2.1CAL <- tkradiobutton(SaisiCal,state="disabled")
assign("rbValue.MCAL", tclVar(modelPrior),envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
n.iter=tclVar(nuPrior)
nu<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_nu, row=6,column=0, sticky="w")
tkgrid(nu, row=6,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
n.iter=tclVar(Study$Sd)
sd.<-tkentry(SaisiCal,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=7,column=0, sticky="w")
tkgrid(sd., row=7,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(Study$Intcpt)}
else {tclVar("NA")}
assign("intcpt.",tkentry(SaisiCal, textvariable=n.iter, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,bg = "cornflower blue",state="disabled")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,bg="cornflower blue",state="disabled")
tkgrid(Validation, row=2)
}
PriorCalib=function(...)
{
.Crea.f.CAL=function(...)
{
assign("TargetPrior",as.numeric(tclvalue(tkget((Target.cal)))), envir = as.environment(pos))
assign("halfwidthPrior",as.numeric(tclvalue(tkget((halfwidth)))), envir = as.environment(pos))
assign("nuPrior",as.numeric(tclvalue(tkget(nu))), envir = as.environment(pos))
assign("nlevel",as.numeric(tclvalue(tkget((slider_Nb_DL.CAL)))), envir = as.environment(pos))
assign("modelPrior",as.numeric(tclvalue(((rbValue.MCAL)))), envir = as.environment(pos))
assign("sdPrior",as.numeric(tclvalue(tkget((sd.)))), envir = as.environment(pos))
assign("intcptPrior",as.numeric(tclvalue(tkget((intcpt.)))), envir = as.environment(pos))
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
if (TargetPrior>0.55) cat("\n Warning: Target DLT rate too high")
if (TargetPrior<0.15) cat("\n Warning: Target DLT rate too low")
if ((halfwidthPrior<=0)|(halfwidthPrior>0.5)) stop('Halfwidth of the indifference intervals incorrect!')
if ((halfwidthPrior<=0.5)&(halfwidthPrior>0.2)) cat("\n Warning: Try to reduce the value of the halfwidth of the indifference intervals ")
if ((nuPrior<1)|(nuPrior>Nb_Niv_DosesCAL)|(nuPrior%%1 != 0)) stop(paste('Prior guess of MTD incorrect, enter an integer between 1 and',Nb_Niv_DosesCAL))
if (modelPrior==1)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel=8, model="logistic", intcpt=intcptPrior)
}
if (modelPrior==2)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel=8, model="empiric")
}
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(round(e$prior[i],3))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,textvariable=n.iter),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_DosesCAL!=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
f.CALPrior=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8),envir = as.environment(pos)),row=r,column=1)
}
if(Nb_Niv_DosesCAL !=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Param.choice = function(...)
{
if (as.numeric(tclvalue((rbValue.MCAL)))==2)
{
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(SaisiCal, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale)
assign("intcpt.",tkentry(SaisiCal, width=10),envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar('8')
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",command=f.CALPrior)
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
Target.cal<-tkentry(SaisiCal, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
halfwidth<-tkentry(SaisiCal, width=10)
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
rb2.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
assign("rbValue.MCAL", tclVar(1), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
sd.<-tkentry(SaisiCal, width=10)
tkgrid(Tsd., row=4,column=2, sticky="w")
tkgrid(sd., row=4,column=3, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
nu<-tkentry(SaisiCal, width=10)
tkgrid(lab_nu, row=7,column=0, sticky="w")
tkgrid(nu, row=7,column=1, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,command=.Crea.f.CAL,bg="cornflower blue")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,command=remplireRequid,bg="cornflower blue")
tkgrid(Validation, row=2)
}
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.crml or file.clsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
if (filef != "") {
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
}
if (extension == "crml") {
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$CRM.2 <- CRM.2
Open.CRM()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
}
}
if (extension == "lsim") {
load(file =paste(paste(names_Study,'clsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS, envir = as.environment(pos))
tkdestroy(Win_CRML)
frameInitSIM()
disabled.SimCRM()
}
}
pending_listing=function()
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
dataa=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(dataa)==0 )
{
msg <- paste("No patient pending",sep="")
tkmessageBox(message=msg)
}
if (nrow(dataa)>=1)
{
assign("tt.pend", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(tt.pend, "+650+400")
assign("tl", tklistbox(tt.pend,height=4,selectmode="single",background="white"), envir = as.environment(pos))
tkgrid(tklabel(tt.pend,text="Select a patient",font=PoliceGenerale))
tkgrid(tl)
numPatP=paste("Patient N'", as.character(dataa$patid),sep="")
for (i in (1:length(numPatP)))
{
tkinsert(tl,"end",numPatP[i])
}
tkselection.set(tl,0)
OK.but <- tkbutton(tt.pend,text=" OK ",command=.include.pending,bg="cornflower blue")
tkgrid(OK.but)
tkfocus(tt.pend)
}
}
.include.pending <- function()
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
data.pinding=Res$PT.data[which(Res$PT.data$pndg==1),]
data.inclus=Res$PT.data[which(Res$PT.data$pndg==0),]
numPatP=as.character(data.pinding$patid)
assign("Choice", as.numeric(numPatP[as.numeric(tkcurselection(tl))+1]), envir = as.environment(pos))
Inc=tktoplevel()
tkwm.geometry(Inc, "+650+400")
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre<-tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i))))
}
.Sauv2=function(...)
{
assign("DLT", as.numeric(tclvalue((rbValue.DLT))), envir = as.environment(pos))
Newpat=data.pinding[which(data.pinding$patid==Choice),]
Newpat$DLT=DLT
Newpat$pndg=0
DATA=rbind(data.inclus,Newpat)
if (nrow(DATA)!=0)
{
if (sum(DATA[,2])==0)
{
numpat=length(DATA[,2])+1
if (numpat!=1)
{
print('numpat')
print(numpat)
temp <- (numpat-1)/3
print('temp')
print(temp)
if (temp==trunc(temp))
{
print('temp==trunc(temp)')
print(trunc(temp))
Res$MTD <- DATA$DL[numpat-1]+1
if (Res$MTD>Study$Nb_Dl){Res$MTD <-DATA$DL[numpat-1]}
}
else
{Res$MTD <-DATA$DL[numpat-1]}
}
}
else
{
environment()
e$CRM.2 <- dfcrm::crm(prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1], conf.level = 0.95,
method = "mle", model = paste(Study$Model.n), intcpt=Study$Intcpt, scale=Study$Sd)
Res$MTD<-e$CRM.2$mtd
}
}
Res$PT.data[which(Res$PT.data$patid==Choice),]$pndg=0
Res$PT.data[which(Res$PT.data$patid==Choice),]$DLT=DLT
if (nrow(DATA)!=0) {
if (sum(DATA[,2])==0) {
save(Res,Study,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))}
else {CRM.2<- e$CRM.2; save(Res,Study,CRM.2,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))}
}
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRML", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRML,text="Validate",width=30,command=.Sauv2,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRML)
tkdestroy (tt.pend)
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-likelihood approach (CRML) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(Study$Model))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(Study$Stop))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRML,text="New patient",width=30,command=.include,bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRML,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRML, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_CRML)
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-likelihood approach (CRML) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(Study$Model))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(Study$Stop))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRML,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRML,text="Pending patient",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.CRML ,"Results")
tkgrid(Rec.Win_CRML, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
if (nrow(DATA)!=0)
{
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRML,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRML,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRML, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2]),
envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
if (!is.null(e$CRM.2)){
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for (i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,
total.tox=total.tox, ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="17",background="white")
tkgrid(t.d, row=2, column=0)
} else {print('Results are displayed once toxicity is observed')}
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],
Toxicity=Res$PT.data[,2])
if (!is.null(e$CRM.2)) {
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,total.tox=total.tox,
ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
Da=data.frame(Study[1],Study[2],Study[4],Study[5],method="Continued reassessment method-likelihood approach (CRML) ",Res[2],Res[1])
DD=t(Da)
rownames(DD)=c("Name of study","Number of dose level","Target DLT rate","Model","Statistical method","Number of patients included", "Estimated MTD")
colnames(DD)=""
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
GrapheResults()
dev.off()
pdf(paste(paste(filef,"2",sep=""),"pdf",sep="."))
curvesIC()
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
setColWidths(wb, sheet2, cols=c(3,4), widths = 14.43)
setColWidths(wb, sheet2, cols=c(1,2,5,6,7), widths = 10.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:7,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}else {
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
writeDataTable(wb,sheet1,x=myRarray1)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
}
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphic",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=Export.Graph,bg="cornflower blue")
button3b=tkbutton(Resultas ,text="Dose-tox curves",width=20,command=Export.CurvesIC,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(button3b, row=5, column=3)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.include=function(...)
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
assign("Inc", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for ( i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
tkgrid(assign(paste('rDLT',2,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=2, text=paste("pending"))))
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))), envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))), envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1), envir = as.environment(pos))
assign("pndg", as.numeric (c(Res$PT.data[,4],as.numeric(tclvalue((rbValue.DLT)))==2)), envir = as.environment(pos))
Res$PT.data <- data.frame(DL=DL,DLT=DLT,patid=patid,pndg=pndg)
Res$Pat.included <- Res$Pat.included+1
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
if (nrow(DATA)!=0)
{
if (sum(DATA[,2])==0)
{
print('3+3')
numpat=length(DATA[,2])+1
if (numpat!=1)
{
temp <- (numpat-1)/3
if (temp==trunc(temp))
{
Res$MTD <- DATA$DL[numpat-1]+1
if (Res$MTD>Study$Nb_Dl){Res$MTD <-DATA$DL[numpat-1]}}
else
{Res$MTD <-DATA$DL[numpat-1]}
}
save(Res,Study,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
}
else
{
e$CRM.2 <- dfcrm::crm(prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1], conf.level = 0.95,
method = "mle", model =paste(Study$Model.n), intcpt=Study$Intcpt, scale=Study$Sd)
Res$MTD <- e$CRM.2$mtd
print('CRM')
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
}
}
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRML", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRML,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRML)
}
GrapheResults=function(...)
{
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
n=length(DATA[,1])
x=c(1:n)
y=DATA[,1]
z=DATA[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
Export.Graph=function()
{
GrapheResults()
}
curvesIC = function(...)
{
post.var <- e$CRM.2$post.var
crit <- qnorm(0.5 + e$CRM.2$conf.level/2)
doses=e$CRM.2$dosescaled
Fempi=function(doses,beta){doses^(exp(beta))}
Flogi=function(doses,beta){(1 + exp(-e$CRM.2$intcpt- exp(beta) * doses))^{-1}}
Fmodel <- switch(e$CRM.2$model,empiric=Fempi, logistic=Flogi)
plot(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),'l', lwd=2,xaxt="n",
ylim=c(0, 1),xlab="Dose level", ylab="Proba. of DLT")
axis(1, at = seq(1, length(e$CRM.2$prior), by = 1))
abline(h=e$CRM.2$target,col="blue",lty=2,lwd=2)
objtitle <-rbind("Dose-toxicity curve + 0.95_IC",paste(e$CRM.2$model, "model"))
title(main=objtitle)
legend('topright',c("Proba. of DLT", "IC(0.95)","target"),lty=c(1,1,2), col=c('black','red','blue'),lwd=2)
points(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),lwd=2)
if (post.var >= 0) {
lb <- e$CRM.2$estimate - crit * sqrt(post.var)
ub <- e$CRM.2$estimate + crit * sqrt(post.var)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,lb),col="red",lwd=2)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,ub),col="red",lwd=2)
}else{print('Confidence interval not calculated')}
}
Export.CurvesIC=function()
{
if (!is.null(e$CRM.2)) {
curvesIC()
}else {print('Results are displayed once toxicity is observed')}
}
NewCRM=function()
{
tkdestroy(Win_CRML)
frameInitCRM()
PriorCalib()
}
disabled.CRM=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.CRM=function()
{
tkdestroy(Win_CRML)
frameInitCRM()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(Study$Sd)
sd.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tsd., row=6,column=2, sticky="w")
tkgrid(sd., row=6,column=3, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
n.iter <- tclVar(Study$Intcpt)
assign("intcpt.", tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
Titre=tklabel(Saisi,text="Names of study",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(Titre, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save Study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
WordExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
docx( ) %>%
addFlexTable(dframe %>%
FlexTable(header.cell.props = cellProperties( background.color = "#003366"),
header.text.props = textBold(color = "white"),
add.rownames = TRUE ) %>%
setZebraStyle(odd = "#DDDDDD", even = "#FFFFFF")) %>%
writeDoc(file = "ResExport.docx")
Save.word.infos <- tkmessageBox(title = "Word Export",
message = "File ResExport.docx saved in the current working directory of the R proces", icon = "info", type = "ok")
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','CRML',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'clsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'clsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
vect.X0=NULL
for (i in 1:StudyS$Npat)
{
vect.X0[i]=as.numeric(tclvalue(tkget(eval(parse(text = paste('valx',i,sep=''))))))
}
StudyS$X0 = vect.X0
if(is.unsorted(StudyS$X0)|(sum(is.na(StudyS$X0))==1)){stop(paste('Initial design must be a non-decreasing sequence of dose levels of length', StudyS$Npat))}
if(any(StudyS$X0<1)|any(StudyS$X0>StudyS$Nb_Dl)|any(StudyS$X0%%1 != 0)) stop(paste('Initial design incorrect, enter a sequence of dose levels between 1 and',StudyS$Nb_Dl))
assign("StudyS", StudyS, envir = as.environment(pos))
cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim <- dfcrm::crmsim(PI=StudyS$True, prior=StudyS$Prior,
target=StudyS$Target,n=StudyS$Npat,x0=StudyS$X0,nsim=StudyS$Nsim,method="mle",
model=StudyS$Model,count=FALSE, intcpt=StudyS$Intcpt, scale=StudyS$Sd, seed=StudyS$Seed)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Maximum likelihood (CRML) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=3)
tk2notetab.select(net.CRML_, "Results")
}
disabled.SimCRM=function()
{
.RecapSimB=function()
{
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Maximum likelihood (CRML) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
tkdestroy(Saisi.design_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
assign("Saisi.design_", tkframe(Design_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.design_, FALSE)
tkgrid(Saisi.design_, row=1, column=1, columnspan=8, rowspan=40)
Nb_Niv_Doses<- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
n_<-tkentry(Saisi_, width=5, textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0[1])
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,state="disabled") ; rb2.1_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Model == "logistic") {
rbValue.M_ <- tclVar(1)
n.intcpt <- tclVar(StudyS$Intcpt)}
if (StudyS$Model == "empiric") {
rbValue.M_ <- tclVar(2)
n.intcpt <- tclVar("NA")}
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation", font=PoliceGenerale)
n.iter <- tclVar(StudyS$Sd)
sd_<-tkentry(Saisi_, width=7, textvariable=n.iter, state="disabled")
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7, textvariable=n.intcpt, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ;
const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
Nb.x0<-StudyS$Npat
for ( i in 1: Nb.x0)
{
n.iter=tclVar(StudyS$X0[i])
if (i <= 15) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i,column=0)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter, state="disabled"),envir = as.environment(pos)),row=i,column=1)
}
if ((i > 15)&&(i <= 30)) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i-15,column=3)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter, state="disabled"),envir = as.environment(pos)),row=i-15,column=4)
}
if (i > 30) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i-30,column=6)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter, state="disabled"),envir = as.environment(pos)),row=i-30,column=7)
}
}
if (Nb.x0 <= 15) {
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
state="disabled",bg="cornflower blue")
tkgrid(ValInitD_, row=16, column=1)}
if ((Nb.x0 > 15)&&(Nb.x0 <= 30)) {
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
state="disabled",bg="cornflower blue")
tkgrid(ValInitD_, row=16, column=4)
}
if (Nb.x0 > 30) {
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
state="disabled",bg="cornflower blue")
tkgrid(ValInitD_, row=16,column=7)
}
.RecapSimB()
}
SimCRM=function()
{
tkdestroy(Win_CRML)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Param.c_= function(...)
{
if (as.numeric(tclvalue((rbValue.M_)))==2)
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=7, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
seed=1
target=as.numeric(tclvalue(tkget((Target_))))
Model=as.numeric(tclvalue((rbValue.M_)))
npat=as.numeric(tclvalue(tkget(n_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
sdv=as.numeric(tclvalue(tkget((sd_))))
seed=as.numeric(tclvalue(tkget((Seed_))))
assign("Names_Study", tclvalue(tkget(names.S_)), envir = as.environment(pos))
if (Model == 1) {model=as.character("logistic"); intcp=as.numeric(tclvalue(tkget((intcpt_))))}
if (Model == 2) {model=as.character("empiric"); intcp=NULL}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if (npat > 80) cat("\n TIP: Might need to maximize the window to validate initial design")
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
if (res.users == 1) {
tkdestroy(Saisi.design_)
assign("Saisi.design_", tkframe(Design_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.design_, FALSE)
tkgrid(Saisi.design_, row=1, column=1, columnspan=8, rowspan=40)
v.x0 <- dfcrm::getinit(prior=prior, target=target, nK=ifelse(npat < Nb_Dl*2, npat,round(npat/Nb_Dl)),n=npat, method = "mle", detail = FALSE)
for ( i in 1: npat)
{
ind <- floor(i/20.01)
n.iter=tclVar(round(v.x0[i],3))
if ((i > ind*20)&&(i <= (ind+1)*20)) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i-ind*20,column=3*ind)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter),envir = as.environment(pos)),row=i-ind*20,column=3*ind+1)
}
}
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
command=.RecapSim,bg="cornflower blue")
tkgrid(ValInitD_, row=21, column=3*ind+1)
tk2notetab.select(net.CRML_, "Initial design")
assign("StudyS", list(Name=paste(Names_Study), Nb_Dl=Nb_Dl, True=true, Prior=prior, Target=target,
Model=model, Npat=npat,Nsim=nsim, X0=v.x0, Intcpt=intcp, Sd=sdv,
Constrain=Const, Seed=seed), envir = as.environment(pos))
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
assign("Target_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
assign("n_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,command=.Param.c_) ; rb2.1_ <- tkradiobutton(Saisi_,command=.Param.c_)
rbValue.M_ <- tclVar(1)
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation",font=PoliceGenerale)
sd_<-tkentry(Saisi_, width=7)
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive CRM or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Continual Reassessment Method with Maximum
likelihood estimation Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=dfcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInitCRM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRML", tktoplevel(background = "black"), envir = as.environment(pos))
tkwm.geometry(Win_CRML, "680x555")
tkwm.geometry(Win_CRML, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRML, ilogo)
tktitle(Win_CRML) <- "GUI CRML"
tkpack.propagate(Win_CRML, FALSE)
topMenu <- tk2menu(Win_CRML)
tkconfigure(Win_CRML, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function (){tkdestroy(Win_CRML);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRML))
assign("net.CRML", tk2notebook(Win_CRML, tabs = c("Prior calibration","Input parameters","Include","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRML , fill = "both", expand = 1)
assign("Include", tk2notetab(net.CRML , "Include"), envir = as.environment(pos))
tkpack.propagate(Include, FALSE)
assign("Resultas", tk2notetab(net.CRML , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.CRML , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("PriorCal", tk2notetab(net.CRML , "Prior calibration"), envir = as.environment(pos))
tkpack.propagate(PriorCal, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.Win_CRML, row=9, column=2, rowspan=16)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL, envir = as.environment(pos))
assign("nuPrior", NULL, envir = as.environment(pos))
assign("etatPrior", FALSE, envir = as.environment(pos))
}
frameInitSIM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRML", tktoplevel(background = "black"), envir = as.environment(pos))
tkwm.geometry(Win_CRML, "680x585")
tkwm.geometry(Win_CRML, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRML, ilogo)
tktitle(Win_CRML) <- "GUI CRML"
tkpack.propagate(Win_CRML, FALSE)
topMenu <- tk2menu(Win_CRML)
tkconfigure(Win_CRML, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function (){tkdestroy(Win_CRML);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRML))
assign("net.CRML_", tk2notebook(Win_CRML, tabs = c("Input parameters","Initial design","Results")), envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRML_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.CRML_ , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Design_", tk2notetab(net.CRML_ , "Initial design"), envir = as.environment(pos))
tkpack.propagate(Design_, FALSE)
assign("Required_", tk2notetab(net.CRML_ , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi.design_", tkframe(Design_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.design_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkpack.propagate(m2_, FALSE)
}
frameInit=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRML", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRML, "630x472")
tkwm.geometry(Win_CRML, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRML, ilogo)
tktitle(Win_CRML) <- "GUI CRML"
tkpack.propagate(Win_CRML, FALSE)
topMenu <- tk2menu(Win_CRML)
tkconfigure(Win_CRML, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study", command=function (){tkdestroy(Win_CRML);frameInit()})
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRML))
}
frameInit()
}
.TITECRM=function(pos=1, e)
{
e$ResSim = NULL
e$CRM.2 = NULL
tclRequire("Tktable")
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
remplireRequid=function()
{
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
Model=as.numeric(tclvalue((rbValue.M)))
if (Model==1){Model.n="logistic"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (Model==2){Model.n="empiric"; intcpt=NULL}
Sdv=as.numeric(tclvalue(tkget(sd.)))
Stop=as.numeric(tclvalue(rbValue.SC))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
ObWin=as.numeric(tclvalue(tkget(ObWin)))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
if (ObWin <= 0 ) stop('Observation window incorrect')
assign("names_Study", tclvalue(tkget(names.S)), envir = as.environment(pos))
assign("Study", list(name=paste(names_Study),Nb_Dl=Nb_Dl,DL=DL,Target=Target,Model=Model,
Model.n=Model.n,Stop=Stop,N_Pat=N_Pat,N_pat_Level=N_pat_Level,Obs.wind=ObWin,
halfwidthPrior=halfwidthPrior,nuPrior=nuPrior, Sd=Sdv, Intcpt=intcpt), envir = as.environment(pos))
differ=abs(Study$DL-Study$Target)
MTD=1
for ( i in 1 : Study$Nb_Dl)
{
if (differ[i]==min(differ)) {MTD=i}
}
Pat_include=0
PT.data=NULL
assign("Res", list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data,ObWin=ObWin), envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(names_Study)
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','TiTE_CRM',sep=':')
a2='TiME TO EVENTS-Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'tcrm', sep='.'))
}
Study.file()
tk2notetab.select(net.TiTECRM , "Include")
}
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
tk2notetab.select(net.TiTECRM , "Input parameters")
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=2, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
priorProbaf <- c()
Nb_Niv_Doses <- nlevel
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (tkget(eval(parse(text = paste('valp',i,sep='')))))
priorProbaf <- c(priorProbaf,as.numeric(tclvalue(n.iter)))
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
if (any(priorProbaf <= 0) | any(priorProbaf >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(priorProbaf, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
SliderValue=tclVar(nlevel)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(TargetPrior)
Target<-tkentry(Saisi, width=5,textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi, state="disabled") ; rb2.1 <- tkradiobutton(Saisi, state="disabled")
rbValue.M <- tclVar(modelPrior)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal S. deviation",font=PoliceGenerale)
n.iter <- tclVar(sdPrior)
sd.<-tkentry(Saisi,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=8,column=0, sticky="w")
tkgrid(sd., row=8,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(intcptPrior)}
else {tclVar("NA")}
assign("intcpt.", tkentry(Saisi, textvariable=n.iter, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=8,column=2, sticky="w")
tkgrid(intcpt., row=8,column=3, sticky="w")
labagewin<-tklabel(Saisi, text="Observation window ",font=PoliceGenerale)
ObWin<-tkentry(Saisi, width=10)
tkgrid(labagewin, row=9,column=0, sticky="w")
tkgrid(ObWin, row=9,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam<- tclVar()
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=10,column=0, sticky="w")
tkgrid(names.S, row=10,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
assign("etatPrior", TRUE, envir = as.environment(pos))
}
disabled.PriorCalib=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
if(is.tkwin(SaisiCal)){tkdestroy(SaisiCal)}
if(is.tkwin(Saisi.saveCal )){tkdestroy(Saisi.saveCal )}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.saveCal, FALSE)
SliderValue.CAL=tclVar(Study$Nb_Dl)
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz", state="disabled")
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
for ( i in 1: Study$Nb_Dl)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar (tkget(eval(parse(text = paste('val',i,sep='')))))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL,text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL,state="disabled", width=8,textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
if( Study$Nb_Dl!=8)
{
for ( i in (Study$Nb_Dl+1):8)
{
r=10 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
n.iter=tclVar(round(TargetPrior,3))
Target.cal<-tkentry(SaisiCal,textvariable=n.iter,state="disabled", width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
n.iter=tclVar(halfwidthPrior)
halfwidth<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_halfwidth, row=3,column=0,columnspan=2, sticky="w")
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal,state="disabled") ; rb2.1CAL <- tkradiobutton(SaisiCal,state="disabled")
assign("rbValue.MCAL", tclVar(modelPrior), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
n.iter=tclVar(nuPrior)
nu<-tkentry(SaisiCal, width=10, textvariable=n.iter, state="disabled")
tkgrid(lab_nu, row=6,column=0, sticky="w")
tkgrid(nu, row=6,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="NormalS. deviation ",font=PoliceGenerale)
n.iter=tclVar(Study$Sd)
sd.<-tkentry(SaisiCal,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=7,column=0, sticky="w")
tkgrid(sd., row=7,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(Study$Intcpt)}
else {tclVar("NA")}
assign("intcpt.", tkentry(SaisiCal, textvariable=n.iter, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,bg = "cornflower blue",state="disabled")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,bg="cornflower blue",state="disabled")
tkgrid(Validation, row=2)
}
PriorCalib=function(...)
{
.Crea.f.CAL=function(...)
{
assign("TargetPrior", as.numeric(tclvalue(tkget((Target.cal)))), envir = as.environment(pos))
assign("halfwidthPrior", as.numeric(tclvalue(tkget((halfwidth)))), envir = as.environment(pos))
assign("nuPrior", as.numeric(tclvalue(tkget(nu))), envir = as.environment(pos))
assign("nlevel", as.numeric(tclvalue(tkget((slider_Nb_DL.CAL)))), envir = as.environment(pos))
assign("modelPrior", as.numeric(tclvalue(((rbValue.MCAL)))), envir = as.environment(pos))
assign("sdPrior", as.numeric(tclvalue(tkget((sd.)))), envir = as.environment(pos))
assign("intcptPrior", as.numeric(tclvalue(tkget((intcpt.)))), envir = as.environment(pos))
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
if (TargetPrior>0.55) cat("\n Warning: Target DLT rate too high")
if (TargetPrior<0.15) cat("\n Warning: Target DLT rate too low")
if ((halfwidthPrior<=0)|(halfwidthPrior>0.5)) stop('Halfwidth of the indifference intervals incorrect!')
if ((halfwidthPrior<=0.5)&(halfwidthPrior>0.2)) cat("\n Warning: Try to reduce the value of the halfwidth of the indifference intervals ")
if ((nuPrior<1)|(nuPrior>Nb_Niv_DosesCAL)|(nuPrior%%1 != 0)) stop(paste('Prior guess of MTD incorrect, enter an integer between 1 and',Nb_Niv_DosesCAL))
if (modelPrior==1)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel,
model="logistic", intcpt=intcptPrior)
}
if (modelPrior==2)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior,
nlevel, model="empiric")
}
for ( i in c(1:Nb_Niv_DosesCAL))
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(round(e$prior[i],3))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,textvariable=n.iter),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_DosesCAL!=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
f.CALPrior=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8),envir = as.environment(pos)),row=r,column=1)
}
if(Nb_Niv_DosesCAL !=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Param.choice = function(...)
{
if (as.numeric(tclvalue((rbValue.MCAL)))==2)
{
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(SaisiCal, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.saveCal, FALSE)
SliderValue.CAL=tclVar('8')
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",command=f.CALPrior)
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
Target.cal<-tkentry(SaisiCal, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
halfwidth<-tkentry(SaisiCal, width=10)
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice) ;
rb2.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
assign("rbValue.MCAL", tclVar(1), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal S. deviation ",font=PoliceGenerale)
sd.<-tkentry(SaisiCal, width=10)
tkgrid(Tsd., row=6,column=0, sticky="w")
tkgrid(sd., row=6,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
nu<-tkentry(SaisiCal, width=10)
tkgrid(lab_nu, row=7,column=0, sticky="w")
tkgrid(nu, row=7,column=1, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,command=.Crea.f.CAL,bg = "cornflower blue")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,command=remplireRequid,bg="cornflower blue")
tkgrid(Validation, row=2)
}
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.tcrm or file.tcsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
if (extension == "tcrm") {
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$CRM.2 <- CRM.2
Open.CRM()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
}
}
if (extension == "csim") {
load(file =paste(paste(names_Study,'tcsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS, envir = as.environment(pos))
tkdestroy(Win_TiTECRM)
frameInitSIM()
disabled.SimCRM()
}
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("TiTE-Continued reassessment method-bayesian approach (TiTECRM) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_TiTECRM,text="New patient",width=30,command=.Include,bg="cornflower blue")
Modif=tkbutton(Rec.Win_TiTECRM,text="Modif patient data",width=30,command=.modif.data.patient,bg="cornflower blue")
tkgrid(Rec.Win_TiTECRM, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
}
.modif.data.patient= function (...)
{
.modif.data=function (...)
{
assign("id.modif", as.numeric(tkcurselection(tlm)) + 1, envir = as.environment(pos))
tkdestroy(tt.modif)
m.data=Res$PT.data[id.modif,]
win.m <- tktoplevel()
dlt. <- tclVar(m.data[,2])
level. <- tclVar(m.data[,1])
followup. <- tclVar(m.data[,4])
lab.id. <- tklabel(win.m,text=paste("Patient N_",id.modif),font=PoliceGenerale)
tkgrid(lab.id., row=0, columnspan=2)
lab.level. <- tklabel(win.m,text=paste("Dose level"),font=PoliceGenerale)
tkgrid(lab.level., row=1, columnspan=2)
assign("win.level", tk2entry(win.m, width = "3", textvariable = level.), envir = as.environment(pos))
tkgrid(win.level,row=1,column=2)
lab.dlt. <- tklabel(win.m,text=paste("DLT (1= 'Yes', 0='No')"),font=PoliceGenerale)
tkgrid(lab.dlt., row=3, columnspan=2)
assign("win.dlt", tk2entry(win.m, width = "3", textvariable = dlt.), envir = as.environment(pos))
tkgrid(win.dlt,row=3,column=2)
lab.fup. <- tklabel(win.m,text=paste("follow-up","<=",Res$ObWin),font=PoliceGenerale)
tkgrid(lab.fup., row=5, columnspan=2)
assign("win.fup", tk2entry(win.m, width = "3", textvariable = followup.), envir = as.environment(pos))
tkgrid(win.fup,row=5,column=2)
onOK <- function() {
new.dlt. <- as.numeric(tclvalue(tkget(win.dlt)))
new.level <- as.numeric(tclvalue(tkget(win.level)))
new.fup <- as.numeric(tclvalue(tkget(win.fup)))
Res$PT.data[id.modif,c(2,1,4)] <- c(new.dlt.,new.level,new.fup)
e$CRM.2 <- dfcrm::titecrm(prior=Study$DL, target=Study$Target, tox=Res$PT.data[,2],level=Res$PT.data[,1], conf.level = 0.95,
model = paste(Study$Model.n), followup=Res$PT.data[,4], obswin=Res$ObWin, intcpt=Study$Intcpt,
scale=Study$Sd)
Res$MTD <- e$CRM.2$mtd
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
tkdestroy(win.m)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
}
win.OK <-tkbutton(win.m, text = "OK", width = 10, command = onOK, bg="cornflower blue")
tkgrid(win.OK)
}
m.data=Res$PT.data
if (is.null(m.data))
{
msg <- paste("No patient included",sep="")
tkmessageBox(message=msg)
}
if (!is.null(m.data))
{
if (nrow(m.data)>=1)
{
tt.modif=tktoplevel()
tkwm.geometry(tt.modif, "+650+400")
assign("tlm", tklistbox(tt.modif,height=nrow(m.data)+1,selectmode="single",background="white"),
envir = as.environment(pos))
tkgrid(tklabel(tt.modif,text="Select a patient",font=PoliceGenerale))
tkgrid(tlm)
patlist=paste(" Patient N_", as.character(m.data$patid),sep="")
for (i in (1:length(patlist)))
{
tkinsert(tlm,"end",patlist[i])
}
tkselection.set(tlm,0)
OK.but <-tkbutton(tt.modif,text=" OK ",command=.modif.data,bg="cornflower blue")
tkgrid(OK.but)
}
}
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_TiTECRM)
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("TiTE-Continued reassessment method-bayesian approach (TiTECRM) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
print('CAS 1')
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_TiTECRM,text="New patient",width=30, state="disabled",bg="cornflower blue")
Modif=tkbutton(Rec.Win_TiTECRM,text="Modif patient data",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.TiTECRM , "Resultas")
print(' Fin CAS 1')
tkgrid(Rec.Win_TiTECRM, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
}
if (nrow(DATA)!=0)
{
print('CAS 2')
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_TiTECRM,text="New patient",width=30, state="disabled",bg="cornflower blue")
Modif=tkbutton(Rec.Win_TiTECRM,text="Modif patient data",width=30,state="disabled",bg="cornflower blue")
tkgrid(Rec.Win_TiTECRM, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
print(' Fin CAS 2')
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2],
followup=Res$PT.data[,4], stringsAsFactors=FALSE), envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, Nb_patient=n.patient,
Nb_tox=total.tox, P_tox=ptox, P_toxL=ptoxL, P_toxU=ptoxU), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="15",background="white")
tkgrid(t.d, row=2, column=0)
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=Res$PT.data[,3],dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2],
followup=Res$PT.data[,4])
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, Nb_patient=n.patient,
Nb_tox=total.tox, P_tox=ptox, P_toxL=ptoxL, P_toxU=ptoxU), envir = as.environment(pos))
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
GrapheResults()
dev.off()
pdf(paste(paste(filef,"2",sep=""),"pdf",sep="."))
curvesIC()
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3,4), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
setColWidths(wb, sheet2, cols=3, widths = 14.43)
setColWidths(wb, sheet2, cols=c(1,2,4,5,6,7), widths = 10.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:4,rows=1)
addStyle(wb,sheet2,style,cols=1:7,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphic",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=Export.Graph,bg="cornflower blue")
button3b=tkbutton(Resultas ,text="Dose-tox curves",width=20,command=Export.CurvesIC,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(button3b, row=5, column=3)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.Include=function(...)
{
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
assign("inc", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(inc, "+550+270")
assign("mm", tkframe(inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(mm)
assign("Titre", tklabel(mm,text="Treated dose level",font=PoliceGenerale), envir = as.environment(pos))
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for ( i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("inc.mm1", tkframe(inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(inc.mm1)
Titre <- tklabel(inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Fup", tkframe(inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Fup)
TitreFup <- tklabel(Fup,text="Follow-up Time")
tkgrid(TitreFup, row=0, columnspan=2)
val=tclVar(Res$ObWin)
assign("Followup", tkentry(Fup,textvariable=val, width=10), envir = as.environment(pos))
tkgrid(Followup)
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))), envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))), envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1), envir = as.environment(pos))
followup2=c(Res$PT.data[,4], as.numeric(tclvalue(tkget((Followup)))))
Res$PT.data<-data.frame(DL=DL,DLT=DLT,patid=patid,followup=followup2)
Res$Pat.included<-Res$Pat.included+1
print(Res$PT.data)
DATA=Res$PT.data
if (nrow(DATA)!=0)
{
e$CRM.2 <- dfcrm::titecrm(prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1], conf.level = 0.95,
model = paste(Study$Model.n), followup=DATA$followup, obswin=Res$ObWin, intcpt=Study$Intcpt,
scale=Study$Sd)
Res$MTD<-e$CRM.2$mtd
}
if (nrow(DATA)!=0){
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))}
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
tkdestroy(inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
inc.Win_TiTECRM<- tkframe(inc,relief="groove",borderwidth=3)
Save=tkbutton(inc.Win_TiTECRM,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(inc.Win_TiTECRM)
}
GrapheResults=function(...)
{
DATA=Res$PT.data
n=length(DATA[,1])
x=c(1:n)
y=DATA[,1]
z=DATA[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
curvesIC = function(...)
{
post.var <- e$CRM.2$post.var
crit <- qnorm(0.5 + e$CRM.2$conf.level/2)
doses=e$CRM.2$dosescaled
Fempi=function(doses,beta){doses^(exp(beta))}
Flogi=function(doses,beta){(1 + exp(-e$CRM.2$intcpt- exp(beta) * doses))^{-1}}
Fmodel <- switch(e$CRM.2$model,empiric=Fempi, logistic=Flogi)
plot(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),'l', lwd=2,xaxt="n",
ylim=c(0, 1),xlab="Dose level", ylab="Proba. of DLT")
axis(1, at = seq(1, length(e$CRM.2$prior), by = 1))
abline(h=e$CRM.2$target,col="blue",lty=2,lwd=2)
objtitle <-rbind("Dose-toxicity curve + 0.95_IC",paste(e$CRM.2$model, "model"))
title(main=objtitle)
legend('topright',c("Proba. of DLT", "IC(0.95)","target"),lty=c(1,1,2), col=c('black','red','blue'),lwd=2)
points(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),lwd=2)
if (post.var >= 0) {
lb <- e$CRM.2$estimate - crit * sqrt(post.var)
ub <- e$CRM.2$estimate + crit * sqrt(post.var)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,lb),col="red",lwd=2)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,ub),col="red",lwd=2)
}else{print('Confidence interval not calculated')}
}
Export.CurvesIC=function()
{
curvesIC()
}
Export.Graph=function()
{
GrapheResults()
}
NewCRM=function()
{
tkdestroy(Win_TiTECRM)
frameInitCRM()
PriorCalib()
}
disabled.CRM=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=2, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Nam_ObWin<- tclVar(Res$ObWin)
labagewin<-tklabel(Saisi, text="Observation window ",font=PoliceGenerale)
ObWin<-tkentry(Saisi, width=10,textvariable=Nam_ObWin,state="disabled")
tkgrid(labagewin, row=8,column=0, sticky="w")
tkgrid(ObWin, row=8,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.CRM=function()
{
tkdestroy(Win_TiTECRM)
frameInitCRM()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=2, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5, textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal S. deviation ",font=PoliceGenerale)
n.iter <- tclVar(Study$Sd)
sd.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tsd., row=6,column=2, sticky="w")
tkgrid(sd., row=6,column=3, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
n.iter <- tclVar(Study$Intcpt)
assign("intcpt.", tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
Nam_ObWin<- tclVar(Res$ObWin)
labagewin<-tklabel(Saisi, text="Observation window ",font=PoliceGenerale)
ObWin<-tkentry(Saisi, width=10,textvariable=Nam_ObWin,state="disabled")
tkgrid(labagewin, row=8,column=0, sticky="w")
tkgrid(ObWin, row=8,column=1, sticky="w")
Titre=tklabel(Saisi,text="Names of study",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(Titre, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
WordExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
docx( ) %>%
addFlexTable(dframe %>%
FlexTable(header.cell.props = cellProperties( background.color = "#003366"),
header.text.props = textBold(color = "white"),
add.rownames = TRUE ) %>%
setZebraStyle(odd = "#DDDDDD", even = "#FFFFFF")) %>%
writeDoc(file = "ResExport.docx")
Save.word.infos <- tkmessageBox(title = "Word Export",
message = "File ResExport.docx saved in the current working directory of the R proces", icon = "info", type = "ok")
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','TITE-CRMB',sep=':')
a2='Time-To-Event Continual Reassessment Method (TITE-CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'tcsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'tcsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-o-Event Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Bayesian approach (TITE-CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Patient arrival rate (per obs. window)"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Rate))
aff_13.0<-tklabel(Rec.fr,text=paste("Patient accrual scheme"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Accrual))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
disabled.SimCRM=function()
{
.RecapSimB=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','TITE-CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'tcsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'tcsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "Files saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-to-Event Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Bayesian approach (TITE-CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Patient arrival rate (per obs. window)"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Rate))
aff_13.0<-tklabel(Rec.fr,text=paste("Patient accrual scheme"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Accrual))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
Nb_Niv_Doses <- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
assign("n_", tkentry(Saisi_, width=5, textvariable=n.iter ,state="disabled"), envir = as.environment(pos))
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model", font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,state="disabled") ; rb2.1_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Model == "logistic") {
rbValue.M_ <- tclVar(1)
n.intcpt <- tclVar(StudyS$Intcpt)}
if (StudyS$Model == "empiric") {
rbValue.M_ <- tclVar(2)
n.intcpt <- tclVar("NA")}
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal S. deviation ", font=PoliceGenerale)
n.iter <- tclVar(StudyS$Sd)
sd_<-tkentry(Saisi_, width=7, textvariable=n.iter, state="disabled")
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7, textvariable=n.intcpt, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Tobsw_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Obswin)
Obsw_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Tobsw_, row=9,column=0, sticky="w")
tkgrid(Obsw_, row=9,column=1, sticky="w")
Trate_<-tklabel(Saisi_, text="Expected number of arrivals per
observation window",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Rate)
Rate_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Trate_, row=10,column=0, sticky="w")
tkgrid(Rate_, row=10,column=1, sticky="w")
Taccrual_=tklabel(Saisi_,text="Patient accrual scheme",font=PoliceGenerale)
rbacc.1_ <- tkradiobutton(Saisi_,state="disabled") ; rbacc.2_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Accrual == "fixed") {rbAcc.M_ <- tclVar(1)}
if (StudyS$Accrual == "poisson") {rbAcc.M_ <- tclVar(2)}
tkconfigure(rbacc.1_,variable=rbAcc.M_,value=1, text="fixed",font=PoliceGenerale)
tkconfigure(rbacc.2_,variable=rbAcc.M_,value=2, text="poisson",font=PoliceGenerale)
tkgrid(Taccrual_, row=11,column=0, sticky="w")
tkgrid(rbacc.1_, row=11,column=1, sticky="w")
tkgrid(rbacc.2_, row=12,column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_,state="disabled") ;
const2_ <- tkradiobutton(Saisi_,state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=11, column=2, sticky="w")
tkgrid(const1_, row=11, column=3, sticky="w")
tkgrid(const2_, row=12,column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size",font=PoliceGenerale)
tkgrid(Tstop_, row=13,column=0,columnspan=4, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=14,column=0, sticky="w")
tkgrid(names.S_,row=14,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimCRM=function()
{
tkdestroy(Win_TiTECRM)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Param.c_= function(...)
{
if (as.numeric(tclvalue((rbValue.M_)))==2)
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=7, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
target=as.numeric(tclvalue(tkget((Target_))))
Model=as.numeric(tclvalue((rbValue.M_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
npat=as.numeric(tclvalue(tkget(n_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
obswin=as.numeric(tclvalue(tkget((Obsw_))))
rate=as.numeric(tclvalue(tkget((Rate_))))
Accrual=as.numeric(tclvalue((rbAcc.M_)))
seed=as.numeric(tclvalue(tkget((Seed_))))
sdv=as.numeric(tclvalue(tkget((sd_))))
assign("Names_Study", tclvalue(tkget(names.S_)), envir = as.environment(pos))
if (Model == 1) {model=as.character("logistic"); intcp=as.numeric(tclvalue(tkget((intcpt_))))}
if (Model == 2) {model=as.character("empiric");intcp=NULL}
if (Accrual == 1) {accrual=as.character("fixed")}
if (Accrual == 2) {accrual=as.character("poisson")}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if (obswin <= 0 ) stop('Observation window incorrect')
if (rate <= 0 ) stop('Expected number of arrivals per observation window must be strictly positive')
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("StudyS", list(Name=paste(Names_Study),Nb_Dl=Nb_Dl,True=true,Prior=prior,Target=target,
Model=model,Npat=npat,Nsim=nsim,X0=x0,Obswin=obswin,
Rate=rate,Accrual=accrual, Intcpt=intcp, Sd=sdv, Constrain=Const, Seed=seed),
envir = as.environment(pos))
if (res.users == 1) {
cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim <- dfcrm::titesim(PI=StudyS$True, prior=StudyS$Prior,target=StudyS$Target,n=StudyS$Npat,
x0=StudyS$X0,nsim=StudyS$Nsim, obswin=StudyS$Obswin, rate=StudyS$Rate,
accrual=StudyS$Accrual, method="bayes",model=StudyS$Model,count=FALSE,
intcpt=StudyS$Intcpt, scale=StudyS$Sd, restrict=StudyS$Constrain, seed=StudyS$Seed)
.RecapSim()
tk2notetab.select(net.TiTECRM_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
assign("Target_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
assign("n_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,command=.Param.c_) ; rb2.1_ <- tkradiobutton(Saisi_,command=.Param.c_)
rbValue.M_ <- tclVar(1)
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal S. deviation",font=PoliceGenerale)
sd_<-tkentry(Saisi_, width=7)
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Tobsw_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
Obsw_<-tkentry(Saisi_, width=10)
tkgrid(Tobsw_, row=9,column=0, sticky="w")
tkgrid(Obsw_, row=9,column=1, sticky="w")
Trate_<-tklabel(Saisi_, text="Expected number of arrivals per
observation window",font=PoliceGenerale)
Rate_<-tkentry(Saisi_, width=10)
tkgrid(Trate_, row=10,column=0, sticky="w")
tkgrid(Rate_, row=10,column=1, sticky="w")
Taccrual_=tklabel(Saisi_,text="Patient accrual scheme",font=PoliceGenerale)
rbacc.1_ <- tkradiobutton(Saisi_) ; rbacc.2_ <- tkradiobutton(Saisi_)
rbAcc.M_ <- tclVar(1)
tkconfigure(rbacc.1_,variable=rbAcc.M_,value=1, text="fixed",font=PoliceGenerale)
tkconfigure(rbacc.2_,variable=rbAcc.M_,value=2, text="poisson",font=PoliceGenerale)
tkgrid(Taccrual_, row=11,column=0, sticky="w")
tkgrid(rbacc.1_, row=11,column=1, sticky="w")
tkgrid(rbacc.2_, row=12,column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=11, column=2, sticky="w")
tkgrid(const1_, row=11, column=3, sticky="w")
tkgrid(const2_, row=12,column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size",font=PoliceGenerale)
tkgrid(Tstop_, row=13,column=0,columnspan=4, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=14,column=0, sticky="w")
tkgrid(names.S_,row=14,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive TITECRM or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Time-to-Event Continual Reassessment Method Bayesian Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=dfcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit=function(){
assign("Win_TiTECRM", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_TiTECRM, "630x500")
tkwm.geometry(Win_TiTECRM, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TiTECRM, ilogo)
tktitle(Win_TiTECRM) <- "GUI TiTE-CRM"
tkpack.propagate(Win_TiTECRM, FALSE)
topMenu <- tk2menu(Win_TiTECRM)
tkconfigure(Win_TiTECRM, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive TiTE-CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="TiTE-CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){tkdestroy(Win_TiTECRM);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TiTECRM))
}
frameInitCRM=function(){
assign("Win_TiTECRM", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_TiTECRM, "680x575")
tkwm.geometry(Win_TiTECRM, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TiTECRM, ilogo)
tktitle(Win_TiTECRM) <- "GUi TiTECRM"
tkpack.propagate(Win_TiTECRM, FALSE)
names_Study=''
topMenu <- tk2menu(Win_TiTECRM)
tkconfigure(Win_TiTECRM, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="Tite-CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){tkdestroy(Win_TiTECRM);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TiTECRM))
assign("net.TiTECRM", tk2notebook(Win_TiTECRM, tabs = c("Prior calibration","Input parameters",
"Include","Results")), envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TiTECRM , fill = "both", expand = 1)
assign("Include", tk2notetab(net.TiTECRM, "Include"), envir = as.environment(pos))
tkpack.propagate(Include, FALSE)
assign("Resultas", tk2notetab(net.TiTECRM, "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.TiTECRM, "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("PriorCal", tk2notetab(net.TiTECRM, "Prior calibration"), envir = as.environment(pos))
tkpack.propagate(PriorCal, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.Win_TiTECRM, row=9, column=2, rowspan=16)
assign("Rec.mm0",tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL, envir = as.environment(pos))
assign("nuPrior", NULL, envir = as.environment(pos))
assign("etatPrior", FALSE, envir = as.environment(pos))
}
frameInitSIM=function(){
assign("Win_TiTECRM", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_TiTECRM, "690x690")
tkwm.geometry(Win_TiTECRM, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TiTECRM, ilogo)
tktitle(Win_TiTECRM) <- "GUi TiTECRM"
tkpack.propagate(Win_TiTECRM, FALSE)
names_Study=''
topMenu <- tk2menu(Win_TiTECRM)
tkconfigure(Win_TiTECRM, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="Tite-CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){tkdestroy(Win_TiTECRM);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TiTECRM))
assign("net.TiTECRM_", tk2notebook(Win_TiTECRM, tabs = c("Input parameters","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TiTECRM_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.TiTECRM_ , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.TiTECRM_ , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkpack.propagate(m2_, FALSE)
}
frameInit()
}
.EWOC=function(pos=1, e)
{
e$EWOC.2 = NULL
e$ResSim = NULL
tclRequire("Tktable")
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.ewoc or file.ewsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
if (filef != "") {
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
}
if (extension == "ewoc") {
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$EWOC.2 <- EWOC.2
Open.EWOC()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(include)
}
}
}
}
if (extension == "wsim") {
load(file =paste(paste(names_Study,'ewsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS, envir = as.environment(pos))
tkdestroy(Win_EWOC)
frameInitSIM()
disabled.SimEWOC()
}
}
pending_listing=function()
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
dataa=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(dataa)==0 )
{
msg <- paste("No patient pending",sep="")
tkmessageBox(message=msg)
}
if (nrow(dataa)>=1)
{
assign("tt.pend", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(tt.pend, "+650+400")
assign("tl", tklistbox(tt.pend,height=4,selectmode="single",background="white"),envir = as.environment(pos))
tkgrid(tklabel(tt.pend,text="Select a patient",font=PoliceGenerale))
tkgrid(tl)
numPatP=paste("Patient N_", as.character(dataa$patid),sep="")
for (i in (1:length(numPatP)))
{
tkinsert(tl,"end",numPatP[i])
}
tkselection.set(tl,0)
OK.but <-tkbutton(tt.pend,text=" OK ",command=.include.pending,bg="cornflower blue")
tkgrid(OK.but)
tkfocus(tt.pend)
}
}
.include.pending <- function()
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
data.pinding=Res$PT.data[which(Res$PT.data$pndg==1),]
data.inclus=Res$PT.data[which(Res$PT.data$pndg==0),]
numPatP=as.character(data.pinding$patid)
assign("Choice", as.numeric(numPatP[as.numeric(tkcurselection(tl))+1]),envir = as.environment(pos))
Inc=tktoplevel()
tkwm.geometry(Inc, "+650+400")
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
assign("rbValue.DLT", tclVar(0),envir = as.environment(pos))
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i))))
}
.Sauv2=function(...)
{
DLT <- as.numeric(tclvalue((rbValue.DLT)))
Newpat=data.pinding[which(data.pinding$patid==Choice),]
Newpat$DLT=DLT
Newpat$pndg=0
DATA=rbind(data.inclus,Newpat)
data.ewoc=DATA[c(3,1,2)]
names(data.ewoc)=c('patient', 'dose','tox')
a=dim(data.ewoc)[1]
if (a>1) {data.ewoc$patient<-c(1:a)}
e$EWOC.2 <- bcrm::bcrm(stop=list(nmax=1),data=data.ewoc,p.tox0=Study$DL,simulate=FALSE,
ff=paste(Study$Model),constrain=Study$Constrain,cohort=1,
prior.alpha=list(Study$Prior.c,Study$a,Study$b),target.tox=Study$Target,
pointest=Study$Pointest,method="rjags")
Res$MTD <- e$EWOC.2$ndose[[1]]$ndose
Res$PT.data[which(Res$PT.data$patid==Choice),]$pndg=0
Res$PT.data[which(Res$PT.data$patid==Choice),]$DLT=DLT
EWOC.2 <- e$EWOC.2
save(Res,Study, EWOC.2,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
Res
tkdestroy(Inc)
assign("Res", Res,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if (Res$Pat.included==1){disabled.EWOC()}
}
Inc.Win_EWOC<- tkframe(Inc,relief="groove",borderwidth=3)
Save=tkbutton(Inc.Win_EWOC,text="Validate",width=30,command=.Sauv2,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_EWOC)
tkdestroy (tt.pend)
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Escalation with overdose control (EWOC) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_EWOC,text="New patient",width=30,command=.include,bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_EWOC,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_EWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_EWOC)
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Escalation with overdose control (EWOC) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_EWOC,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_EWOC,text="Pending patient",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.EWOC , "Results")
tkgrid(Rec.Win_EWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
if (nrow(DATA)!=0)
{
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_EWOC,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_EWOC,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_EWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),
dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2]),envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
Sdose=round(e$EWOC.2$ndose[[1]]$est,3)
n.patient=NULL
total.tox=NULL
Mean=round(e$EWOC.2$ndose[[1]]$mean,3)
SD=round(e$EWOC.2$ndose[[1]]$sd,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for (i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Sdose=Sdose, n.patient=n.patient,
total.tox=total.tox, Post.mean=Mean, Post.sd=SD), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat <- tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2])
Sdose=round(e$EWOC.2$ndose[[1]]$est,3)
n.patient=NULL
total.tox=NULL
Mean=round(e$EWOC.2$ndose[[1]]$mean,3)
SD=round(e$EWOC.2$ndose[[1]]$sd,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 :Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Sdose=Sdose, n.patient=n.patient,
total.tox=total.tox, Post.mean=Mean, Post.sd=SD),envir = as.environment(pos))
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
plot(e$EWOC.2)
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=1:3, widths = 14.43)
setColWidths(wb, sheet2, cols=1:6, widths = 14.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:6,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphic",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=Export.Graph,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.include=function(...)
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
assign("Inc", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for (i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
tkgrid(assign(paste('rDLT',2,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=2, text=paste("pending"))))
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))),envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))),envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1),envir = as.environment(pos))
assign("pndg", as.numeric (c(Res$PT.data[,4],as.numeric(tclvalue((rbValue.DLT)))==2)),envir = as.environment(pos))
Res$PT.data <- data.frame(DL=DL,DLT=DLT,patid=patid,pndg=pndg)
Res$Pat.included <- Res$Pat.included+1
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
data.ewoc=DATA[c(3,1,2)]
names(data.ewoc)=c('patient', 'dose','tox')
a=dim(data.ewoc)[1]
if (a>1) {data.ewoc$patient<-c(1:a)}
if (nrow(DATA)!=0)
{
e$EWOC.2<- bcrm::bcrm(stop=list(nmax=1),data=data.ewoc, p.tox0=Study$DL,
simulate=FALSE, ff=paste(Study$Model), constrain=Study$Constrain, cohort=1,
prior.alpha=list(Study$Prior.c,Study$a,Study$b),target.tox=Study$Target,
pointest=Study$Pointest,method="rjags")
EWOC.2 <- e$EWOC.2
Res$MTD <- e$EWOC.2$ndose[[1]]$ndose
}
if (nrow(DATA)!=0) {
save(Res,Study,EWOC.2,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))}
else {save(Res,Study,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))}
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if (Res$Pat.included==1)
{disabled.EWOC()}
}
Inc.Win_EWOC<- tkframe(Inc,relief="groove",borderwidth=3)
Save=tkbutton(Inc.Win_EWOC,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_EWOC)
}
Export.Graph=function()
{
plot(e$EWOC.2)
}
NewEWOC=function()
{
tkdestroy(Win_EWOC)
frameInitEWOC()
.Crea.f=function(...)
{
Nb_Niv_Doses <- as.numeric(tclvalue((SliderValue)))
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_Doses!=8)
{
for ( i in (Nb_Niv_Doses+1):8)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
model=tclvalue(tkget((model)))
if (model=="Hyperbolic tangent")(Model="ht")
if (model=="Logistic")(Model="logit1")
if (model=="Power")(Model="power")
Prior=tclvalue(tkget((Prior.alpha)))
if (Prior=="Gamma(a,b)")(Prior.c=1)
if (Prior=="Uniform(a,b)")(Prior.c=2)
if (Prior=="Lognormal(a,b)")(Prior.c=3)
a.p=as.numeric(tclvalue(tkget(a)))
b.p=as.numeric(tclvalue(tkget(b)))
pointtest=as.numeric(tclvalue(tkget(pointest)))
Stop=as.numeric(tclvalue(rbValue.SC))
const=as.logical(as.numeric(tclvalue(rbValue.const)))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
assign("names_Study", tclvalue(tkget(names.S)),envir = as.environment(pos))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
if (any(DL <= 0) | any(DL >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(DL, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (Target>0.55) cat("\n Warning: Target DLT rate too high")
if (Target<0.15) cat("\n Warning: Target DLT rate too low")
if ((pointtest < 0) | (pointtest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
assign("Study", list(name=paste(names_Study),Nb_Dl=Nb_Dl,DL=DL,Target=Target,Model=Model,
Stop=Stop,N_Pat=N_Pat,N_pat_Level=N_pat_Level,Prior=Prior,Prior.c=Prior.c,
a.p=a.p,b.p=b.p,Pointest=pointtest, Constrain=const), envir = as.environment(pos))
MTD=max(which(Study$DL==Study$Target),1)
Pat_include=0
PT.data=NULL
assign("Res", list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data),envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(names_Study)
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','EWOC',sep=':')
a2='Escalation With Overdose Control (EWOC) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'ewoc', sep='.'))
}
Study.file()
tk2notetab.select(net.EWOC , "Include")
}
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=14)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
SliderValue=tclVar('8')
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",command=.Crea.f)
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
assign("Target", tkentry(Saisi, width=5),envir = as.environment(pos))
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w", columnspan=2)
tkgrid(NBpat, row=5,column=2, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
model <-tk2spinbox(Saisi, values = c("Hyperbolic tangent","Logistic","Power"))
tkgrid(Titre , row=6,column=0, sticky="w")
tkgrid(model, row=6,column=1, sticky="w")
Titre=tklabel(Saisi,text="Prior",font=PoliceGenerale)
Prior.alpha <-tk2spinbox(Saisi, values = c("Gamma(a,b)","Uniform(a,b)","Lognormal(a,b)"))
tkgrid(Titre , row=7,column=0, sticky="w")
tkgrid(Prior.alpha , row=7,column=1, sticky="w")
Titre1=tklabel(Saisi,text="a",font=PoliceGenerale)
Titre2=tklabel(Saisi,text="b",font=PoliceGenerale)
assign("a", tkentry(Saisi, width=5),envir = as.environment(pos))
assign("b", tkentry(Saisi, width=5),envir = as.environment(pos))
tkgrid(Titre1, row=8, column=0, sticky="w")
tkgrid(a, row=8, column=1, sticky="w")
tkgrid(Titre2, row=8, column=2, sticky="w")
tkgrid(b, row=8, column=3, sticky="w")
Titre1=tklabel(Saisi,text="Pointest in [0,0.5]",font=PoliceGenerale)
assign("pointest", tkentry(Saisi, width=5),envir = as.environment(pos))
tkgrid(Titre1, row=10, column=0, sticky="w")
tkgrid(pointest, row=10, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi) ; const2 <- tkradiobutton(Saisi)
rbValue.const <- tclVar(1)
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=11, column=0, sticky="w")
tkgrid(const1, row=11, column=1, sticky="w")
tkgrid(const2, row=12,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=13,column=0, sticky="w")
tkgrid(names.S, row=13,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
}
disabled.EWOC=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Saisi.save)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=14)
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w", columnspan=2)
tkgrid(NBpat, row=5,column=2, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
model <-tk2spinbox(Saisi, values =paste(Study$Model),state="disabled")
tkgrid(Titre , row=6,column=0, sticky="w")
tkgrid(model, row=6,column=1, sticky="w")
Titre=tklabel(Saisi,text="Prior",font=PoliceGenerale)
Prior.alpha <-tk2spinbox(Saisi, values = paste(Study$Prior),state="disabled")
tkgrid(Titre , row=7,column=0, sticky="w")
tkgrid(Prior.alpha , row=7,column=1, sticky="w")
Titre1=tklabel(Saisi,text="a",font=PoliceGenerale)
Titre2=tklabel(Saisi,text="b",font=PoliceGenerale)
a.iter <- tclVar(Study$a.p);b.iter <- tclVar(Study$b.p)
assign("a", tkentry(Saisi, width=5,textvariable=a.iter ,state="disabled"),envir = as.environment(pos))
assign("b", tkentry(Saisi, width=5,textvariable=b.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=8, column=0, sticky="w")
tkgrid(a, row=8, column=1, sticky="w")
tkgrid(Titre2, row=8, column=2, sticky="w")
tkgrid(b, row=8, column=3, sticky="w")
Titre1=tklabel(Saisi,text="Pointest in [0,0.5]",font=PoliceGenerale)
pointest.iter <- tclVar(Study$Pointest)
assign("pointest", tkentry(Saisi, width=5,textvariable=pointest.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=10, column=0, sticky="w")
tkgrid(pointest, row=10, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi, state="disabled") ; const2 <- tkradiobutton(Saisi, state="disabled")
rbValue.const <- tclVar(as.numeric(Study$Constrain))
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=11, column=0, sticky="w")
tkgrid(const1, row=11, column=1, sticky="w")
tkgrid(const2, row=12,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=13,column=0, sticky="w")
tkgrid(names.S, row=13,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.EWOC=function()
{
tkdestroy(Win_EWOC)
frameInitEWOC()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w", columnspan=2)
tkgrid(NBpat, row=5,column=2, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
model <-tk2spinbox(Saisi, values =paste(Study$Model),state="disabled")
tkgrid(Titre , row=6,column=0, sticky="w")
tkgrid(model, row=6,column=1, sticky="w")
Titre=tklabel(Saisi,text="Prior",font=PoliceGenerale)
Prior.alpha <-tk2spinbox(Saisi, values = paste(Study$Prior),state="disabled")
tkgrid(Titre , row=7,column=0, sticky="w")
tkgrid(Prior.alpha , row=7,column=1, sticky="w")
Titre1=tklabel(Saisi,text="a",font=PoliceGenerale)
Titre2=tklabel(Saisi,text="b",font=PoliceGenerale)
a.iter <- tclVar(Study$a.p);b.iter <- tclVar(Study$b.p)
assign("a", tkentry(Saisi, width=5,textvariable=a.iter ,state="disabled"),envir = as.environment(pos))
assign("b", tkentry(Saisi, width=5,textvariable=b.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=8, column=0, sticky="w")
tkgrid(a, row=8, column=1, sticky="w")
tkgrid(Titre2, row=8, column=2, sticky="w")
tkgrid(b, row=8, column=3, sticky="w")
Titre1=tklabel(Saisi,text="Pointest in [0,0.5]",font=PoliceGenerale)
pointest.iter <- tclVar(Study$Pointest)
assign("pointest", tkentry(Saisi, width=5,textvariable=pointest.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=10, column=0, sticky="w")
tkgrid(pointest, row=10, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi, state="disabled") ; const2 <- tkradiobutton(Saisi, state="disabled")
rbValue.const <-tclVar(as.numeric(Study$Constrain))
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=11, column=0, sticky="w")
tkgrid(const1, row=11, column=1, sticky="w")
tkgrid(const2, row=12,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=13,column=0, sticky="w")
tkgrid(names.S, row=13,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
pdf(paste(filef_,"pdf",sep="."))
plot(e$ResSim2)
dev.off()
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','EWOC',sep=':')
a2='Escalation With Overdose Control (EWOC) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'ewsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'ewsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
Res.print.sim=function() {
n.average <- mean(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.min <- min(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.max <- max(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
assign("n.res", cbind(n.average,n.min,n.max),envir = as.environment(pos))
rec <- sapply(e$ResSim, function(i) {
i$ndose[[length(i$ndose)]]$ndose
})
rec.tab <- prop.table(table(factor(rec, levels = 1:length(e$ResSim[[1]]$tox))))
exp <- sapply(e$ResSim, function(i) {
(i$tox + i$notox)/sum(i$tox + i$notox)
})
exp.tab <- apply(exp, 1, mean)
assign("tab.dose", signif(rbind(exp.tab, rec.tab), 3),envir = as.environment(pos))
tox.cutpoints = NULL
if (is.null(tox.cutpoints)) {
tox.cutpoints <- seq(0, 1, by = 0.2)
} else {
tox.cutpoints <- unique(c(0, tox.cutpoints, 1))
}
assign("exp.tox", signif(prop.table(table(cut(unlist(sapply(e$ResSim, function(i) {
rep(i$truep, (i$tox + i$notox))
}, simplify = FALSE)), tox.cutpoints, include.lowest = T))),2),envir = as.environment(pos))
tox. <- sapply(e$ResSim, function(i) {
(i$tox)
})
assign("tox.tab", apply(tox., 1, mean),envir = as.environment(pos))
}
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
Res.print.sim()
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(tab.dose[2,1],3))
ToxRes=paste(round(tox.tab[1],3))
LevelRes=paste(round(tab.dose[1,1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(tab.dose[2,i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(tab.dose[1,i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(tox.tab[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(ifelse(StudyS$Model=="ht","Hyperbolic tangent",ifelse(StudyS$Model=="logit1","Logistic","Power"))))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size: mean [min,max]"))
aff_7.1<-tklabel(Rec.fr,text=paste(paste(paste(n.res[1]),"[",n.res[2]),",",n.res[3],"]"))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
e$ResSim2 <- e$ResSim
e$ResSim2[[1]]$sdose <- round(e$ResSim[[1]]$sdose,3)
PlotBut=tkbutton(Rec.save_ ,text="Graphic",width=20,command=function(){plot(e$ResSim2)},bg="cornflower blue")
tkgrid(PlotBut, row=1)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(tab.dose[2,],3),
round(tab.dose[1,],3),round(tox.tab,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
disabled.SimEWOC=function()
{
.RecapSimB=function()
{
Res.print.sim = function() {
n.average <- mean(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.min <- min(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.max <- max(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
assign("n.res", cbind(n.average,n.min,n.max),envir = as.environment(pos))
rec <- sapply(e$ResSim, function(i) {
i$ndose[[length(i$ndose)]]$ndose
})
rec.tab <- prop.table(table(factor(rec, levels = 1:length(e$ResSim[[1]]$tox))))
exp <- sapply(e$ResSim, function(i) {
(i$tox + i$notox)/sum(i$tox + i$notox)
})
exp.tab <- apply(exp, 1, mean)
assign("tab.dose", signif(rbind(exp.tab, rec.tab), 3),envir = as.environment(pos))
tox.cutpoints = NULL
if (is.null(tox.cutpoints)) {
tox.cutpoints <- seq(0, 1, by = 0.2)
} else {
tox.cutpoints <- unique(c(0, tox.cutpoints, 1))
}
assign("exp.tox", signif(prop.table(table(cut(unlist(sapply(e$ResSim, function(i) {
rep(i$truep, (i$tox + i$notox))
}, simplify = FALSE)), tox.cutpoints, include.lowest = T))),2),envir = as.environment(pos))
tox. <- sapply(e$ResSim, function(i) {
(i$tox)
})
assign("tox.tab", apply(tox., 1, mean),envir = as.environment(pos))
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
Res.print.sim()
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(tab.dose[2,1],3))
ToxRes=paste(round(tox.tab[1],3))
LevelRes=paste(round(tab.dose[1,1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(tab.dose[2,i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(tab.dose[1,i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(tox.tab[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(ifelse(StudyS$Model=="ht","Hyperbolic tangent",ifelse(StudyS$Model=="logit1","Logistic","Power"))))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size: mean [min,max]"))
aff_7.1<-tklabel(Rec.fr,text=paste(paste(paste(n.res[1]),"[",n.res[2]),",",n.res[3],"]"))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
e$ResSim2 <- e$ResSim
e$ResSim2[[1]]$sdose<-round(e$ResSim[[1]]$sdose,3)
PlotBut=tkbutton(Rec.save_ ,text="Graphic",width=20,command=function(){plot(e$ResSim2)},bg="cornflower blue")
tkgrid(PlotBut, row=1)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(tab.dose[2,],3),
round(tab.dose[1,],3),round(tox.tab,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=8)
Nb_Niv_Doses <- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0,columnspan=4, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=3, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0,columnspan=3, sticky="w")
tkgrid(Target_, row=2, column=3, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0,columnspan=3, sticky="w")
tkgrid(Nsim_, row=4,column=3, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0,columnspan=3, sticky="w")
tkgrid(X0_, row=5,column=3, sticky="w")
if (StudyS$Model=="ht")(model="Hyperbolic tangent")
if (StudyS$Model=="logit1")(model="Logistic")
if (StudyS$Model=="power")(model="Power")
if (StudyS$Prior.a==1)(prior.a="Gamma(a,b)")
if (StudyS$Prior.a==2)(prior.a="Uniform(a,b)")
if (StudyS$Prior.a==3)(prior.a="Lognormal(a,b)")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
Model_ <-tk2spinbox(Saisi_, values = paste(model),state="disabled")
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=2,columnspan=3, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=7,column=0,columnspan=4, sticky="w")
tkgrid(Seed_, row=7,column=4, sticky="w")
Tstop_=tklabel(Saisi_,text="Stopping rule",font=PoliceGenerale)
rbstop.1_ <- tkradiobutton(Saisi_,state="disabled") ; rbstop.2_ <- tkradiobutton(Saisi_,state="disabled")
if (!is.null(StudyS$Nmax)){rbstop.M_ <- tclVar(1)}
if (!is.null(StudyS$Nmtd)){rbstop.M_ <- tclVar(2)}
tkconfigure(rbstop.1_,variable=rbstop.M_,value=1, text="Maximum sample size",font=PoliceGenerale)
tkconfigure(rbstop.2_,variable=rbstop.M_,value=2, text="Maximum number of patients treated at final MTD",font=PoliceGenerale)
tkgrid(Tstop_, row=8,column=0,columnspan=3, sticky="w")
tkgrid(rbstop.1_, row=8,column=3,columnspan=3, sticky="w")
tkgrid(rbstop.2_, row=9,column=3,columnspan=5, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients corresponding",font=PoliceGenerale)
if (!is.null(StudyS$Nmax)){n.iter <- tclVar(StudyS$Nmax)}
if (!is.null(StudyS$Nmtd)){n.iter <- tclVar(StudyS$Nmtd)}
assign("N_", tkentry(Saisi_,width=5,textvariable=n.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Tnum_, row=10, column=0,columnspan=4, sticky="w")
tkgrid(N_, row=10, column=4, sticky="w")
Tpriora_=tklabel(Saisi_,text="Prior Alpha",font=PoliceGenerale)
Prior.alpha_ <-tk2spinbox(Saisi_, values =paste(prior.a),state="disabled")
tkgrid(Tpriora_ , row=11,column=0,columnspan=2, sticky="w")
tkgrid(Prior.alpha_ , row=11,column=2,columnspan=3, sticky="w")
Ta_=tklabel(Saisi_,text="a",font=PoliceGenerale)
Tb_=tklabel(Saisi_,text="b",font=PoliceGenerale)
na <- tclVar(StudyS$a)
nb <- tclVar(StudyS$b)
assign("a_", tkentry(Saisi_, width=5,textvariable=na ,state="disabled"),envir = as.environment(pos))
assign("b_", tkentry(Saisi_, width=5,textvariable=nb ,state="disabled"),envir = as.environment(pos))
tkgrid(Ta_, row=12, column=0, sticky="w")
tkgrid(a_, row=12, column=1, sticky="w")
tkgrid(Tb_, row=12, column=2, sticky="w")
tkgrid(b_, row=12, column=3, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0,0.5]",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Pointest)
assign("pointest_", tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Tpoint_, row=13, column=0,columnspan=2, sticky="w")
tkgrid(pointest_, row=13, column=2, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ; const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=14, column=0, sticky="w")
tkgrid(const1_, row=14, column=1, sticky="w")
tkgrid(const2_, row=15,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=16,column=0,columnspan=2, sticky="w")
tkgrid(names.S_, row=16,column=2,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimEWOC=function()
{
tkdestroy(Win_EWOC)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
seed=1
target=as.numeric(tclvalue(tkget((Target_))))
nmax=NULL
nmtd=NULL
Stopr=as.numeric(tclvalue((rbstop.M_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
Model=tclvalue(tkget((Model_)))
if (Model=="Hyperbolic tangent")(model="ht")
if (Model=="Logistic")(model="logit1")
if (Model=="Power")(model="power")
Prior=tclvalue(tkget((Prior.alpha_)))
if (Prior=="Gamma(a,b)")(Prior.a=1)
if (Prior=="Uniform(a,b)")(Prior.a=2)
if (Prior=="Lognormal(a,b)")(Prior.a=3)
a.p=as.numeric(tclvalue(tkget(a_)))
b.p=as.numeric(tclvalue(tkget(b_)))
pointest=as.numeric(tclvalue(tkget(pointest_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
seed=as.numeric(tclvalue(tkget((Seed_))))
assign("Names_Study", tclvalue(tkget(names.S_)),envir = as.environment(pos))
if (Stopr == 1) {nmax=as.numeric(tclvalue(tkget(N_)))}
if (Stopr == 2) {nmtd=as.numeric(tclvalue(tkget(N_)))}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (Stopr == 1) {
if (nmax <=0) stop('Number of patients to be enrolled <=0')
if (nmax > 100) cat("\n Warning: Number of patients to be enrolled > 100")
}
if (Stopr == 2) {
if (nmtd <= 0) stop('Number of patients treated at final MTD <=0')
if (nmtd > 20) cat("\n Warning: Number of patients treated at final MTD > 20")
}
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if ((pointest < 0) | (pointest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("StudyS", list(Name=paste(Names_Study),Nb_Dl=Nb_Dl,True=true,Prior=prior,Target=target,
Model=model,Prior.a=Prior.a,a=a.p,b=b.p,Nmax=nmax,Nmtd=nmtd,Pointest=pointest,
Nsim=nsim,X0=x0,Seed=seed, Constrain=Const),envir = as.environment(pos))
if (res.users == 1) { cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim<- bcrm::bcrm(stop=list(nmax=StudyS$Nmax,nmtd=StudyS$Nmtd),p.tox0=StudyS$Prior,
truep=StudyS$True,ff=StudyS$Model, target.tox=StudyS$Target, cohort=1,
prior.alpha=list(StudyS$Prior.a,StudyS$a,StudyS$b), pointest=StudyS$Pointest,
start=StudyS$X0,simulate=TRUE,nsims=StudyS$Nsim,method="rjags",quietly=TRUE,
constrain=StudyS$Constrain, seed=StudyS$Seed)
.RecapSim()
tk2notetab.select(net.EWOC_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0,columnspan=4, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=3, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
assign("Target_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Titre_, row=2, column=0,columnspan=3, sticky="w")
tkgrid(Target_, row=2, column=3, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0,columnspan=3, sticky="w")
tkgrid(Nsim_, row=4,column=3, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0,columnspan=3, sticky="w")
tkgrid(X0_, row=5,column=3, sticky="w")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
Model_ <-tk2spinbox(Saisi_, values = c("Hyperbolic tangent","Logistic","Power"))
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=2,columnspan=3, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=7,column=0,columnspan=4, sticky="w")
tkgrid(Seed_, row=7,column=4, sticky="w")
Tstop_=tklabel(Saisi_,text="Stopping rule",font=PoliceGenerale)
rbstop.1_ <- tkradiobutton(Saisi_) ; rbstop.2_ <- tkradiobutton(Saisi_)
rbstop.M_ <- tclVar(1)
tkconfigure(rbstop.1_,variable=rbstop.M_,value=1, text="Maximum sample size",font=PoliceGenerale)
tkconfigure(rbstop.2_,variable=rbstop.M_,value=2, text="Maximum number of patients treated at final MTD",font=PoliceGenerale)
tkgrid(Tstop_, row=8,column=0,columnspan=3, sticky="w")
tkgrid(rbstop.1_, row=8,column=3,columnspan=3, sticky="w")
tkgrid(rbstop.2_, row=9,column=3,columnspan=5, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients corresponding",font=PoliceGenerale)
assign("N_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Tnum_, row=10, column=0,columnspan=4, sticky="w")
tkgrid(N_, row=10, column=4, sticky="w")
Tpriora_=tklabel(Saisi_,text="Prior Alpha",font=PoliceGenerale)
Prior.alpha_ <-tk2spinbox(Saisi_, values = c("Gamma(a,b)","Uniform(a,b)","Lognormal(a,b)"))
tkgrid(Tpriora_ , row=11,column=0,columnspan=2, sticky="w")
tkgrid(Prior.alpha_ , row=11,column=2,columnspan=3, sticky="w")
Ta_=tklabel(Saisi_,text="a",font=PoliceGenerale)
Tb_=tklabel(Saisi_,text="b",font=PoliceGenerale)
assign("a_", tkentry(Saisi_, width=5),envir = as.environment(pos));
assign("b_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Ta_, row=12, column=0, sticky="w")
tkgrid(a_, row=12, column=1, sticky="w")
tkgrid(Tb_, row=12, column=2, sticky="w")
tkgrid(b_, row=12, column=3, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0,0.5]",font=PoliceGenerale)
assign("pointest_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Tpoint_, row=13, column=0,columnspan=2, sticky="w")
tkgrid(pointest_, row=13, column=2, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=14, column=0, sticky="w")
tkgrid(const1_, row=14, column=1, sticky="w")
tkgrid(const2_, row=15,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=16,column=0,columnspan=2, sticky="w")
tkgrid(names.S_, row=16,column=2,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive EWOC or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Escalade With Overdose Control Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=bcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit=function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_EWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_EWOC, "630x550")
tkwm.geometry(Win_EWOC, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_EWOC, ilogo)
tktitle(Win_EWOC) <- "GUI EWOC"
tkpack.propagate(Win_EWOC, FALSE)
topMenu <- tk2menu(Win_EWOC)
tkconfigure(Win_EWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive EWOC", command=NewEWOC)
tkadd(newStudyMenu,"command", label="EWOC simulator", command=SimEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_EWOC); frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_EWOC))
}
frameInitEWOC=function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_EWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_EWOC, "630x610")
tkwm.geometry(Win_EWOC, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_EWOC, ilogo)
tktitle(Win_EWOC) <- "GUI EWOC"
tkpack.propagate(Win_EWOC, FALSE)
names_Study=''
topMenu <- tk2menu(Win_EWOC)
tkconfigure(Win_EWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive EWOC", command=NewEWOC)
tkadd(newStudyMenu,"command", label="EWOC simulator", command=SimEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_EWOC); frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_EWOC))
assign("net.EWOC", tk2notebook(Win_EWOC, tabs = c("Input parameters","Include","Results")),envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.EWOC , fill = "both", expand = 1)
assign("include", tk2notetab(net.EWOC , "Include"),envir = as.environment(pos))
tkpack.propagate(include, FALSE)
assign("Resultas", tk2notetab(net.EWOC , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.EWOC , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.Win_EWOC, row=9, column=2, rowspan=16)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL,envir = as.environment(pos))
assign("nuPrior", NULL,envir = as.environment(pos))
assign("etatPrior", FALSE,envir = as.environment(pos))
}
frameInitSIM=function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_EWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_EWOC, "765x700")
tkwm.geometry(Win_EWOC, "+460+100")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_EWOC, ilogo)
tktitle(Win_EWOC) <- "GUI EWOC"
tkpack.propagate(Win_EWOC, FALSE)
names_Study=''
topMenu <- tk2menu(Win_EWOC)
tkconfigure(Win_EWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive EWOC", command=NewEWOC)
tkadd(newStudyMenu,"command", label="EWOC simulator", command=SimEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_EWOC); frameInit()})
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_EWOC))
assign("net.EWOC_", tk2notebook(Win_EWOC, tabs = c("Input parameters","Results")),envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.EWOC_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.EWOC_ , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.EWOC_ , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=0, columnspan=2, rowspan=7)
}
frameInit()
}
.TEWOC=function(pos=1, e)
{
e$TEWOC. = NULL
e$ResSim = NULL
tclRequire("Tktable")
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.tewoc or file.tewsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
if (filef != "") {
stu=read.table(filef,header=TRUE)
assign("Names_Study", paste(stu[1,]),envir = as.environment(pos))
extension<-str_sub(filef,-6)
}
if (extension == ".tewoc") {
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
e$TEWOC. <- TEWOC.
disabled.TEWOC()
.ReCap.Resultat()
if (Res$Pat.included >= Study$Npat)
{ cat('Maximal number of patients reached out', "\n")
disabled.Recap()
}else { .ReCap() }
}
if (extension == "tewsim") {
load(file =paste(paste(Names_Study,'tewsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS,envir = as.environment(pos))
tkdestroy(Win_TEWOC)
frameInitSIM()
disabled.SimTEWOC()
}
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.include=function(...)
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
assign("mess", tkmessageBox(message = "Do you want to enter mutiple patient data at the same time?",
icon = "question", type = "yesno", default = "yes"),envir = as.environment(pos))
if (tclvalue(mess)=="no") {
assign("Inc", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for (i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.tox <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rtox',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.tox ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Fup", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Fup)
TitreFup <- tklabel(Fup,text="Follow-up Time")
tkgrid(TitreFup, row=0, columnspan=2)
val = tclVar(Study$Obs.wind)
assign("Followup", tkentry(Fup,textvariable=val, width=10),envir = as.environment(pos))
tkgrid(Followup)
} else if (tclvalue(mess)=="yes") {
Police <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
assign("Inc", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
tkwm.geometry(Inc, "505x230")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(mm)
Rules <- tklabel(mm,text="The data must be separated with comma (ex: 1,1,2)",font=Police)
tkgrid(Rules, row=0, columnspan=2)
space0 <- tklabel(mm, text=" ")
tkgrid(space0, row=1, column=0)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=2, column=0)
level. <- tkentry(mm, width=60)
tkgrid(level., row=2, column=1)
space1 <- tklabel(mm, text=" ")
tkgrid(space1, row=3, column=0)
Ttox <- tklabel(mm,text="DLT (0=No, 1=Yes)",font=PoliceGenerale)
tkgrid(Ttox, row=4, column=0)
tox. <- tkentry(mm, width=60)
tkgrid(tox., row=4, column=1)
space2 <- tklabel(mm, text=" ")
tkgrid(space2, row=5, column=0)
TFup <- tklabel(mm,text=paste("Follow-up","<=",Study$Obs.wind,sep=' '),
font=PoliceGenerale)
tkgrid(TFup, row=6, column=0)
Fup. <- tkentry(mm, width=60)
tkgrid(Fup., row=6, column=1)
}
.Sauv=function(...)
{
if (tclvalue(mess)=="yes") {
assign("DL", c(Res$PT.data[,1],as.numeric(c(do.call("cbind",strsplit(tclvalue(tkget(level.)),","))))),envir = as.environment(pos))
assign("tox", c(Res$PT.data[,2],as.numeric(c(do.call("cbind",strsplit(tclvalue(tkget(tox.)),","))))),envir = as.environment(pos))
assign("fup",c(Res$PT.data[,4],as.numeric(c(do.call("cbind",strsplit(tclvalue(tkget(Fup.)),","))))),envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],c((Res$Pat.included+1):(length(DL)))),envir = as.environment(pos))
Res$Pat.included=length(patid)
} else {
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue(rbValue.DL))),envir = as.environment(pos))
assign("tox", c(Res$PT.data[,2],as.numeric(tclvalue(rbValue.tox))),envir = as.environment(pos))
Res$Pat.included<-Res$Pat.included+1
assign("patid", c(Res$PT.data[,3],Res$Pat.included),envir = as.environment(pos))
assign("fup", c(Res$PT.data[,4],as.numeric(tclvalue(tkget(Followup)))),envir = as.environment(pos))
}
Res$PT.data <- data.frame(DL=DL,Tox=tox,patid=patid,Fup=fup)
e$TEWOC. <- .titeewoc(prior=Study$Prior, target=Study$Target, tox=Res$PT.data[,2],
level=Res$PT.data[,1], followup=Res$PT.data[,4], obswin=Study$Obs.wind,
pointest=Study$Pointest, method="rjags", model=Study$Model, intcpt=Study$Intcpt,
p.dist=Study$P.dist, p1=Study$P1, p2=Study$P2, alphap=Study$Alphap, constrain= Study$Constrain)
Res$MTD <- e$TEWOC.$dose.rec
TEWOC. <- e$TEWOC.
save(Res,Study,TEWOC.,file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if(Res$Pat.included==Study$Npat)
{
disabled.Recap()
}
if(Res$Pat.included > Study$Npat)
{
disabled.Recap()
Save.infos <- tkmessageBox(title = "Stopping rule",
message = "More patients than expected were included",
icon = "warning", type = "ok")
}
}
Inc.Win_EWOC<- tkframe(Inc,relief="groove",borderwidth=3)
Save=tkbutton(Inc.Win_EWOC,text="Validate",width=10,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_EWOC)
}
.ReCap=function(...)
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
priorp=paste(Study$Prior[1])
for( i in 2 : length(Study$Prior))
{
priorp=paste(priorp,paste(Study$Prior[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(priorp))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Time-to-Event Escalation With Overdose Control (Tite-EWOC)"))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste("Sample size"))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$Npat))
affiche_10.0<-tklabel(Rec.mm0,text=paste("Observation window "))
affiche_10.1<-tklabel(Rec.mm0,text=paste(Study$Obs.wind))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
tkgrid(affiche_10.0, row=11, column=1, sticky="w")
tkgrid(affiche_10.1, row=11, column=2, sticky="w")
tkconfigure(affiche_10.0, font=Policeligne )
tkconfigure(affiche_10.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_TEWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_TEWOC,text="New patient",width=30,command=.include,bg="cornflower blue")
Modif=tkbutton(Rec.Win_TEWOC,text="Modif patient data",width=30,command=.modif.data.patient,bg="cornflower blue")
tkgrid(Rec.Win_TEWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
}
.modif.data.patient= function (...)
{
.modif.data=function (...)
{
assign("id.modif", as.numeric(tkcurselection(tlm)) + 1, envir = as.environment(pos))
tkdestroy(tt.modif)
m.data=Res$PT.data[id.modif,]
win.m <- tktoplevel()
dlt. <- tclVar(m.data[,2])
level. <- tclVar(m.data[,1])
followup. <- tclVar(m.data[,4])
lab.id. <- tklabel(win.m,text=paste("Patient N_",id.modif),font=PoliceGenerale)
tkgrid(lab.id., row=0, columnspan=2)
lab.level. <- tklabel(win.m,text=paste("Dose level"),font=PoliceGenerale)
tkgrid(lab.level., row=1, columnspan=2)
assign("win.level", tk2entry(win.m, width = "3", textvariable = level.),envir = as.environment(pos))
tkgrid(win.level,row=1,column=2)
lab.dlt. <- tklabel(win.m,text=paste("DLT (1= 'Yes', 0='No')"),font=PoliceGenerale)
tkgrid(lab.dlt., row=3, columnspan=2)
assign("win.dlt", tk2entry(win.m, width = "3", textvariable = dlt.),envir = as.environment(pos))
tkgrid(win.dlt,row=3,column=2)
lab.fup. <- tklabel(win.m,text=paste("follow-up","<=",Study$Obs.wind),font=PoliceGenerale)
tkgrid(lab.fup., row=5, columnspan=2)
assign("win.fup", tk2entry(win.m, width = "3", textvariable = followup.),envir = as.environment(pos))
tkgrid(win.fup,row=5,column=2)
onOK <- function() {
new.dlt. <- as.numeric(tclvalue(tkget(win.dlt)))
new.level <- as.numeric(tclvalue(tkget(win.level)))
new.fup <- as.numeric(tclvalue(tkget(win.fup)))
Res$PT.data[id.modif,c(2,1,4)] <- c(new.dlt.,new.level,new.fup)
e$TEWOC. <- .titeewoc(prior=Study$Prior, target=Study$Target, tox=Res$PT.data[,2],
level=Res$PT.data[,1], followup=Res$PT.data[,4], obswin=Study$Obs.wind,
pointest=Study$Pointest, method="rjags", model=Study$Model, intcpt=Study$Intcpt,
p.dist=Study$P.dist, p1=Study$P1, p2=Study$P2, alphap=Study$Alphap, constrain= Study$Constrain)
Res$MTD <- e$TEWOC.$dose.rec
TEWOC. <- e$TEWOC.
save(Res,Study,TEWOC.,file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
tkdestroy(win.m)
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
}
win.OK <-tkbutton(win.m, text = "OK", width = 10, command = onOK, bg="cornflower blue")
tkgrid(win.OK)
}
assign("m.data", Res$PT.data,envir = as.environment(pos))
if (is.null(m.data))
{
msg <- paste("No patient included",sep="")
tkmessageBox(message=msg)
}
if (!is.null(m.data))
{
if (nrow(m.data)>=1)
{
assign("tt.modif", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(tt.modif, "+650+400")
assign("tlm", tklistbox(tt.modif,height=nrow(m.data)+1,selectmode="single",background="white"),envir = as.environment(pos))
tkgrid(tklabel(tt.modif,text="Select a patient",font=PoliceGenerale))
tkgrid(tlm)
patlist=paste(" Patient N_", as.character(m.data$patid),sep="")
for (i in (1:length(patlist)))
{
tkinsert(tlm,"end",patlist[i])
}
tkselection.set(tlm,0)
OK.but <-tkbutton(tt.modif,text=" OK ",command=.modif.data,bg="cornflower blue")
tkgrid(OK.but)
}
}
}
disabled.Recap=function(...)
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
priorp=paste(Study$Prior[1])
for( i in 2 : length(Study$Prior))
{
priorp=paste(priorp,paste(Study$Prior[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(priorp))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Time-to-Event Escalation With Overdose Control (Tite-EWOC)"))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste("Sample size"))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$Npat))
affiche_10.0<-tklabel(Rec.mm0,text=paste("Observation window "))
affiche_10.1<-tklabel(Rec.mm0,text=paste(Study$Obs.wind))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
tkgrid(affiche_10.0, row=11, column=1, sticky="w")
tkgrid(affiche_10.1, row=11, column=2, sticky="w")
tkconfigure(affiche_10.0, font=Policeligne )
tkconfigure(affiche_10.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="blue")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="blue")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_TEWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_TEWOC,text="New patient",width=30,state="disabled",bg="cornflower blue")
tkgrid(Rec.Win_TEWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
Modif=tkbutton(Rec.Win_TEWOC,text="Modif patient data",width=30,state="disabled",bg="cornflower blue")
tkgrid(Modif, row=0, column=1)
}
.ReCap.Resultat <- function ()
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
ResultsPat <- function() {
myRarray. <- data.frame(dose_level=Res$PT.data[,1],
Toxicity=Res$PT.data[,2],Follow_up=Res$PT.data[,4])
rownames(myRarray.) <- c(1:dim(myRarray.)[1])
rownames(myRarray.) <- paste0("Pat N_ ",rownames(myRarray.))
tclarray. <- tclArrayVar(myRarray.)
print.tclArrayVar(tclarray.)
}
ResultsbyLevel<- function() {
prior=e$TEWOC.$prior
n.patient=e$TEWOC.$nb.pat.level
total.tox=e$TEWOC.$nb.tox.level
m.weight=round(e$TEWOC.$weights.m.level,3)
quantiles=signif(t(e$TEWOC.$quantiles.ptox[c(1,3,5),]),3)
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=prior, Nb.patient=n.patient,
Total.tox=total.tox,mean.weight=m.weight,q=quantiles),envir = as.environment(pos))
rownames(myRarray2) <- c(1:dim(myRarray2)[1])
rownames(myRarray2) <- paste0("dose ",rownames(myRarray2))
tclarray2 <- tclArrayVar(myRarray2)
print.tclArrayVar(tclarray2)
}
ExportRes <- function() {
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
n=length(Res$PT.data[,1])
x=c(1:n)
y=Res$PT.data[,1]
z=Res$PT.data[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
dev.off()
ggsave(plot=.plot.titeewoc(e$TEWOC.) , filename=paste(paste(filef,"boxplot",sep=""),"pdf",sep="."))
myRarray. <- data.frame(dose_level=Res$PT.data[,1],
Toxicity=Res$PT.data[,2],Follow_up=Res$PT.data[,4])
rownames(myRarray.) <- c(1:dim(myRarray.)[1])
rownames(myRarray.) <- paste0("Pat N_ ",rownames(myRarray.))
prior=e$TEWOC.$prior
n.patient=e$TEWOC.$nb.pat.level
total.tox=e$TEWOC.$nb.tox.level
m.weight=round(e$TEWOC.$weights.m.level,3)
quantiles=signif(t(e$TEWOC.$quantiles.ptox[c(1,3,5),]),3)
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=prior, Nb.patient=n.patient,
Total.tox=total.tox,mean.weight=m.weight,q=quantiles), envir = as.environment(pos))
rownames(myRarray2) <- c(1:dim(myRarray2)[1])
rownames(myRarray2) <- paste0("dose ",rownames(myRarray2))
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=1:3, widths = 14.43)
setColWidths(wb, sheet2, cols=1:8, widths = 14.43)
writeDataTable(wb,sheet1,x=myRarray.)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:8,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
GrapheResults = function(...)
{
n=length(Res$PT.data[,1])
x=c(1:n)
y=Res$PT.data[,1]
z=Res$PT.data[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
GrapheGG = function()
{
print(.plot.titeewoc(e$TEWOC.))
}
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
l5<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Toxicity plot",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Toxicity Prob boxplot",font=PoliceTitre)
Titre.5=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Summary",width=20,command=ResultsPat,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Summary",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=GrapheResults,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Graphic",width=20,command=GrapheGG,bg="cornflower blue")
button5=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkconfigure(Titre.4, font=PoliceTitre)
tkgrid(button4, row=7, column=2)
tkgrid(l5, row=8, column=1)
tkgrid(Titre.5, row=9, column=1, sticky="w")
tkgrid(button5, row=9, column=2)
tkconfigure(button5,padx=2)
tkconfigure(Titre.5, font=PoliceTitre)
}
disabled.TEWOC=function()
{
tkdestroy(Win_TEWOC)
frameInitTEWOC()
Nb_Niv_Doses <- Study$Nb_Dl
assign("m2", tkframe(Required, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=15)
assign("Saisi.save", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$Prior[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=4)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=5)
}
SliderValue<-tclVar(Nb_Niv_Doses)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=2, sticky="w")
Titre <-tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar (Study$Target)
Target <-tkentry(Saisi, width=5, textvariable=n.iter, state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Tmod = tklabel(Saisi,text="Model",font=PoliceGenerale)
n.iter <- switch (Study$Model, ht="Hyperbolique tangent",
power="Power", logit1="1-Logistic")
Model <- tk2spinbox(Saisi, values = c( n.iter,""),width=19, state="disabled")
tkgrid(Tmod , row=6,column=0, sticky="w")
tkgrid(Model, row=6,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
intcpt <- if (is.null(Study$Intcpt))
{ c("NA") }
else { Study$Intcpt}
n.intcpt <- tclVar(intcpt)
assign("intcpt.", tkentry(Saisi, width=10, textvariable=n.intcpt, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
Tstop=tklabel(Saisi,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop, row=7,column=0,columnspan=4, sticky="w")
Tnum=tklabel(Saisi,text="Number of patients corresponding",font=PoliceGenerale)
n.iter <- tclVar(Study$Npat)
N <- tkentry(Saisi, width=5, textvariable=n.iter, state="disabled")
tkgrid(Tnum, row=8, column=0, columnspan=2, sticky="w")
tkgrid(N, row=8, column=2, sticky="w")
Tpdist = tklabel(Saisi,text="Prior alpha dist. ",font=PoliceGenerale)
n.iter <- switch (Study$P.dist, unif="Uniform [p1,p2]",
gamma="Gamma (p1,p2)")
Pdist <- tk2spinbox(Saisi, values = c(n.iter,""), width=15, state="disabled")
tkgrid(Tpdist , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist, row=9,column=1, sticky="w")
Talpha=tklabel(Saisi,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1=tklabel(Saisi,text="p1",font=PoliceGenerale)
Tp2=tklabel(Saisi,text="p2",font=PoliceGenerale)
n.al <- tclVar(Study$Alphap); n.p1 <- tclVar(Study$P1)
n.p2 <- tclVar(Study$P2)
alpha<-tkentry(Saisi, width=7, textvariable=n.al, state="disabled")
p1<-tkentry(Saisi, width=7, textvariable=n.p1, state="disabled")
p2<-tkentry(Saisi, width=7, textvariable=n.p2, state="disabled")
tkgrid(Tp1, row=10, column=0, sticky="w")
tkgrid(p1, row=10, column=1, sticky="w")
tkgrid(Tp2, row=10, column=2, sticky="w")
tkgrid(p2, row=10, column=3, sticky="w")
tkgrid(Talpha, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha, row=11, column=2, sticky="w")
Tpoint = tklabel(Saisi, text="Pointest in [0, 0.5]",font=PoliceGenerale)
n. <- tclVar(Study$Pointest)
point <- tkentry(Saisi, width=10, textvariable=n., state="disabled")
tkgrid(Tpoint, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point, row=12, column=1, sticky="w")
Titrec =tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi, state="disabled") ;
const2 <- tkradiobutton(Saisi, state="disabled")
rbValue.const <- tclVar(as.numeric(Study$Constrain))
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1, row=12, column=4, sticky="w")
tkgrid(const2, row=13,column=4, sticky="w")
Twind<-tklabel(Saisi, text="Observation window",font=PoliceGenerale)
n.obs <- tclVar(Study$Obs.wind)
Wind<-tkentry(Saisi, width=10, textvariable=n.obs, state="disabled")
tkgrid(Twind, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind, row=13,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(Study$Name)
names.S<-tkentry(Saisi, width=18, textvariable=Nam_, state="disabled")
tkgrid(labage, row=14, column=0, sticky="w")
tkgrid(names.S, row=14, column=1,columnspan=2, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled", bg="cornflower blue")
tkgrid(Save.rec, row=1)
}
NewTEWOC=function()
{
tkdestroy(Win_TEWOC)
frameInitTEWOC()
.Crea.f=function(...)
{
Nb_Niv_Doses <- as.numeric(tclvalue((SliderValue)))
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_Doses!=8)
{
for ( i in (Nb_Niv_Doses+1):8)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
disp.int=function()
{
if (!(tclvalue(tkget(Model))=="1-Logistic"))
{
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(Saisi, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(Saisi, width=10),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
}
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
prior=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),
as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),
as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),
as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
npat=NULL
alphap=1
target=as.numeric(tclvalue(tkget((Target))))
pointest=as.numeric(tclvalue(tkget(point)))
const=as.logical(as.numeric(tclvalue((rbValue.const))))
model.=tclvalue(tkget(Model))
intcpt=NULL
if (model. == "Hyperbolic tangent") model = "ht"
if (model. == "1-Logistic") {model = "logit1"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (model. == "Power") model = "power"
pdist.=tclvalue(tkget(Pdist))
if (pdist. == "Uniform [p1,p2]") pdist = "unif"
if (pdist. == "Gamma (p1,p2)") pdist = "gamma"
npat=as.numeric(tclvalue(tkget((N))))
alphap=as.numeric(tclvalue(tkget((alpha))))
p2=as.numeric(tclvalue(tkget((p2))))
p1=as.numeric(tclvalue(tkget((p1))))
twind=as.numeric(tclvalue(tkget(Wind)))
assign("Names_Study", tclvalue(tkget(names.S)),envir = as.environment(pos))
if (npat <=0) stop('Number of patients to be enrolled in the study <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if (twind <= 0 ) stop('Observation window incorrect')
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if ((pointest < 0) | (pointest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
assign("Study", list(Name=paste(Names_Study), Nb_Dl=Nb_Dl, Prior=prior, Target=target,
P.dist=pdist, P1=p1, P2=p2, Model=model, Alphap=alphap, Intcpt=intcpt,
Method="rjags", Npat=npat, Pointest=pointest, Obs.wind=twind, Constrain=const),
envir = as.environment(pos))
MTD <- max(which.min(abs(Study$Prior-Study$Target)),1)
Pat_Include <- 0
PT.data <- NULL
assign ("Res", list(MTD=MTD,Pat.included=Pat_Include,PT.data=PT.data,Obs.wind=Study$Obs.wind),
envir = as.environment(pos))
save(Res,Study,file =paste(paste(Study$Name,'tewoc',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(Study$Name)
a0=paste('Name of study',paste(Study$Name),sep=':')
a1=paste('Method','Tite-EWOC',sep=':')
a2='Time-to-Event Escalation With Overdose Control (Tite-EWOC) for Phase I Clinical Trials'
datee <- paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(Study$Name),'tewoc', sep='.'))
}
Study.file()
tk2notetab.select(net.TEWOC , "Include")
}
assign("Saisi", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=15)
assign("Saisi.save", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
assign("m2", tkframe(Required, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
SliderValue<-tclVar('8')
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",command=.Crea.f)
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=2, sticky="w")
Titre <-tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
Target <-tkentry(Saisi, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Tmod = tklabel(Saisi,text="Model",font=PoliceGenerale)
Model <- tk2spinbox(Saisi, values = c("Hyperbolic tangent","1-Logistic","Power"),width=17, command=disp.int)
tkgrid(Tmod , row=6,column=0, sticky="w")
tkgrid(Model, row=6,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(Saisi, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
Tstop=tklabel(Saisi,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop, row=7,column=0,columnspan=4, sticky="w")
Tnum=tklabel(Saisi,text="Number of patients corresponding",font=PoliceGenerale)
N <- tkentry(Saisi, width=5)
tkgrid(Tnum, row=8, column=0, columnspan=2, sticky="w")
tkgrid(N, row=8, column=2, sticky="w")
Tpdist = tklabel(Saisi,text="Prior alpha dist. ",font=PoliceGenerale)
Pdist <- tk2spinbox(Saisi, values = c("Uniform [p1,p2]","Gamma (p1,p2)"),width=15)
tkgrid(Tpdist , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist, row=9,column=1, sticky="w")
Talpha=tklabel(Saisi,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1=tklabel(Saisi,text="p1",font=PoliceGenerale)
Tp2=tklabel(Saisi,text="p2",font=PoliceGenerale)
alpha<-tkentry(Saisi, width=7)
p1<-tkentry(Saisi, width=7);p2<-tkentry(Saisi, width=7)
tkgrid(Tp1, row=10, column=0, sticky="w")
tkgrid(p1, row=10, column=1, sticky="w")
tkgrid(Tp2, row=10, column=2, sticky="w")
tkgrid(p2, row=10, column=3, sticky="w")
tkgrid(Talpha, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha, row=11, column=2, sticky="w")
Tpoint = tklabel(Saisi, text="Pointest in [0, 0.5]",font=PoliceGenerale)
point <- tkentry(Saisi, width=10)
tkgrid(Tpoint, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point, row=12, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi) ;
const2 <- tkradiobutton(Saisi)
rbValue.const <- tclVar(1)
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1, row=12, column=4, sticky="w")
tkgrid(const2, row=13,column=4, sticky="w")
Twind<-tklabel(Saisi, text="Observation window",font=PoliceGenerale)
Wind<-tkentry(Saisi, width=10)
tkgrid(Twind, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind, row=13,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
names.S<-tkentry(Saisi, width=18)
tkgrid(labage, row=14, column=0, sticky="w")
tkgrid(names.S, row=14, column=1,columnspan=2, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study, bg="cornflower blue")
tkgrid(Save.rec, row=1)
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','Tite-EWOC',sep=':')
a2='Time-to-Event Escalation With Overdose Control (Tite-EWOC) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'tewsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'tewsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(e$ResSim$pct.dose.rec[1],3))
ToxRes=paste(round(e$ResSim$nb.tox.level[1]/e$ResSim$nsim,3))
LevelRes=paste(round(e$ResSim$pat.level[1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$pct.dose.rec[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$pat.level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$nb.tox.level[i]/e$ResSim$nsim,3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
model <- switch (StudyS$Model, ht="hyperbolique tangent",
power="Power", logit1="1-logistic")
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-to-Event Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(model))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$samplesize))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Mean inter-patient arrival time"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Tmean.arrival))
aff_13.0<-tklabel(Rec.fr,text=paste("Observation window"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Obs.wind))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(e$ResSim$pct.dose.rec,3),
round(e$ResSim$pat.level,3),round(e$ResSim$nb.tox.level,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
disabled.SimTEWOC=function()
{
.RecapSimB=function()
{
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(e$ResSim$pct.dose.rec[1],3))
ToxRes=paste(round(e$ResSim$nb.tox.level[1]/e$ResSim$nsim,3))
LevelRes=paste(round(e$ResSim$pat.level[1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$pct.dose.rec[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$pat.level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$nb.tox.level[i]/e$ResSim$nsim,3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
model <- switch (StudyS$Model, ht="hyperbolique tangent",
power="Power", logit1="1-logistic")
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-to-Event Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(model))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$samplesize))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Mean inter-patient arrival time"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Tmean.arrival))
aff_13.0<-tklabel(Rec.fr,text=paste("Observation window"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Obs.wind))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(e$ResSim$pct.dose.rec,3),
round(e$ResSim$pat.level,3),round(e$ResSim$nb.tox.level/e$ResSim$nsim,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
Nb_Niv_Doses <- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=3)
tkgrid(assign(paste('labp',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=4)
tkgrid(assign(paste('valp',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=5)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=2, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Strt.dose)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
n.iter <- switch (StudyS$Model, ht="Hyperbolique tangent",
power="Power", logit1="1-Logistic")
Model_ <- tk2spinbox(Saisi_, values = c(n.iter,"") ,state="disabled")
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=1, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
intcpt <- if (is.null(StudyS$Intcpt))
{ c("NA") }
else { StudyS$Intcpt}
n.intcpt <- tclVar(intcpt)
assign("intcpt_", tkentry(Saisi_, width=10,textvariable=n.intcpt, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6,column=2, sticky="w")
tkgrid(intcpt_, row=6,column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop_, row=7,column=0,columnspan=4, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
N_<-tkentry(Saisi_,width=5,textvariable=n.iter ,state="disabled")
tkgrid(Tnum_, row=8, column=0, sticky="w")
tkgrid(N_, row=8, column=1, sticky="w")
Tpdist_ = tklabel(Saisi_,text="Prior alpha dist. ",font=PoliceGenerale)
n.iter <- switch (StudyS$P.dist, unif="Uniform [p1,p2]",
gamma="Gamma (p1,p2)")
Pdist_ <- tk2spinbox(Saisi_, values = c(n.iter,""), width=15, state="disabled")
tkgrid(Tpdist_ , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist_, row=9,column=1, sticky="w")
Talpha_=tklabel(Saisi_,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1_=tklabel(Saisi_,text="p1",font=PoliceGenerale)
Tp2_=tklabel(Saisi_,text="p2",font=PoliceGenerale)
n.al <- tclVar(StudyS$Alpha); n.p1 <- tclVar(StudyS$P1)
n.p2 <- tclVar(StudyS$P2)
alpha_<-tkentry(Saisi_, width=7, textvariable=n.al, state="disabled")
p1_<-tkentry(Saisi_, width=7, textvariable=n.p1, state="disabled")
p2_<-tkentry(Saisi_, width=7, textvariable=n.p2, state="disabled")
tkgrid(Tp1_, row=10, column=0, sticky="w")
tkgrid(p1_, row=10, column=1, sticky="w")
tkgrid(Tp2_, row=10, column=2, sticky="w")
tkgrid(p2_, row=10, column=3, sticky="w")
tkgrid(Talpha_, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha_, row=11, column=2, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0, 0.5]",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Pointest)
point_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tpoint_, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point_, row=12, column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ;
const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1_, row=12, column=4, sticky="w")
tkgrid(const2_, row=13,column=4, sticky="w")
Twind_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Obs.wind)
Wind_<-tkentry(Saisi_,textvariable=n.iter, width=10,state="disabled")
tkgrid(Twind_, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind_, row=13,column=1, sticky="w")
Tparr_<-tklabel(Saisi_, text="Mean inter-patient arrival time",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Tmean.arrival)
Parr_<-tkentry(Saisi_,textvariable=n.iter, width=10,state="disabled")
tkgrid(Tparr_, row=14,column=0,columnspan=3, sticky="w")
tkgrid(Parr_, row=14,column=2, sticky="w")
Tacc_<-tklabel(Saisi_, text="Accrual",font=PoliceGenerale)
Acc_<-tk2spinbox(Saisi_, values = c(StudyS$Accrual),width=7,state="disabled")
tkgrid(Tacc_, row=15,column=0, sticky="w")
tkgrid(Acc_, row=15,column=1, sticky="w")
Ttox_<-tklabel(Saisi_, text="Time until toxicity occurence",font=PoliceGenerale)
n.iter <- switch(StudyS$Toxocc, unif="uniform", exp="exponential")
tox_<-tk2spinbox(Saisi_, values = c(n.iter), width=10, state="disabled")
tkgrid(Ttox_, row=16,column=0,columnspan=3, sticky="w")
tkgrid(tox_, row=16,column=2, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=17,column=0,columnspan=2, sticky="w")
tkgrid(Seed_, row=17,column=2, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=18,column=0, sticky="w")
tkgrid(names.S_, row=18,column=1,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimTEWOC=function()
{
tkdestroy(Win_TEWOC)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_ <- as.numeric(tclvalue((SliderValue_)))
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
tkgrid(assign(paste('labp',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=4)
tkgrid(assign(paste('valp',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=5)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
tkgrid(assign(paste('labp',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=4)
tkgrid(assign(paste('valp',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=5)
}
}
}
disp.int_=function()
{
if (!(tclvalue(tkget(Model_))=="1-Logistic"))
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6,column=2, sticky="w")
tkgrid(intcpt_, row=6,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=10),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6, column=2, sticky="w")
tkgrid(intcpt_, row=6, column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
true=NULL
prior=NULL
if (Nb_Dl==2) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))))}
if (Nb_Dl==3) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))))}
if (Nb_Dl==4) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),as.numeric(tclvalue(tkget(valp4))))}
if (Nb_Dl==5) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))))}
if (Nb_Dl==6) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))),as.numeric(tclvalue(tkget(valp6))))}
if (Nb_Dl==7) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),
as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),
as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))),as.numeric(tclvalue(tkget(valp6))),as.numeric(tclvalue(tkget(valp7))))}
if (Nb_Dl==8) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),
as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),
as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),
as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))),as.numeric(tclvalue(tkget(valp6))),
as.numeric(tclvalue(tkget(valp7))),as.numeric(tclvalue(tkget(valp8))))}
seed=NULL
npat=NULL
alpha=1
target=as.numeric(tclvalue(tkget((Target_))))
pointest=as.numeric(tclvalue(tkget(point_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
model.=tclvalue(tkget(Model_))
intcpt=NULL
if (model. == "Hyperbolic tangent") model = "ht"
if (model. == "1-Logistic") {model = "logit1"; intcpt=intcpt=as.numeric(tclvalue(tkget(intcpt_)))}
if (model. == "Power") model = "power"
toxocc <- switch(tclvalue(tkget(tox_)), uniform="unif", exponential="exp")
pdist_=tclvalue(tkget(Pdist_))
if (pdist_ == "Uniform [p1,p2]") pdist = "unif"
if (pdist_ == "Gamma (p1,p2)") pdist = "gamma"
accrual=tclvalue(tkget(Acc_))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
npat=as.numeric(tclvalue(tkget((N_))))
alpha=as.numeric(tclvalue(tkget((alpha_))))
p2=as.numeric(tclvalue(tkget((p2_))))
p1=as.numeric(tclvalue(tkget((p1_))))
twind=as.numeric(tclvalue(tkget(Wind_)))
tparr=as.numeric(tclvalue(tkget(Parr_)))
seed=as.numeric(tclvalue(tkget((Seed_))))
assign("Names_Study", tclvalue(tkget(names.S_)),envir = as.environment(pos))
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if ((pointest < 0) | (pointest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
if (twind <= 0 ) stop('Observation window incorrect')
if (tparr <= 0 ) stop('Mean inter patient arrival time must be strictly positive')
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("StudyS", list(Name=paste(Names_Study),Nb_Dl=Nb_Dl, True=true, Prior=prior,Target=target,
P1=p1, P2=p2, Model=model, Accrual=accrual, Alpha=alpha, P.dist=pdist,
Method="rjags", Npat=npat, Pointest=pointest, Toxocc=toxocc, Intcpt=intcpt, Constrain=Const,
Nsim=nsim, Strt.dose=x0, Obs.wind=twind, Tmean.arrival=tparr, Seed=seed),envir = as.environment(pos))
if(res.users == 1) {
cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim <- .titeewocsim(nsim=StudyS$Nsim, true=StudyS$True, prior=StudyS$Prior, target=StudyS$Target,
obswin = StudyS$Obs.wind, tparr = StudyS$Tmean.arrival, accrual = StudyS$Accrual,
start = StudyS$Strt.dose, samplesize = StudyS$Npat, method = StudyS$Method,
pointest=StudyS$Pointest, model = StudyS$Model, toxocc=StudyS$Toxocc,
constrain = StudyS$Constrain, p1 = StudyS$P1, p2=StudyS$P2, p.dist=StudyS$P.dist,
alphap = StudyS$Alpha, count= FALSE, intcpt=StudyS$Intcpt,
seed=StudyS$Seed, burnin.itr = 2000, production.itr = 2000)
.RecapSim()
tk2notetab.select(net.TEWOC_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_ <- tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=2, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
Target_<-tkentry(Saisi_, width=5)
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
Model_ <-tk2spinbox(Saisi_, values = c("Hyperbolic tangent","1-Logistic","Power"), command=disp.int_)
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=1, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6, column=2, sticky="w")
tkgrid(intcpt_, row=6, column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop_, row=7,column=0,columnspan=4, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients",font=PoliceGenerale)
N_<-tkentry(Saisi_, width=5)
tkgrid(Tnum_, row=8, column=0, sticky="w")
tkgrid(N_, row=8, column=1, sticky="w")
Tpdist_ = tklabel(Saisi_,text="Prior alpha dist. ",font=PoliceGenerale)
Pdist_ <- tk2spinbox(Saisi_, values = c("Uniform [p1,p2]","Gamma (p1,p2)"),width=15)
tkgrid(Tpdist_ , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist_, row=9,column=1, sticky="w")
Talpha_=tklabel(Saisi_,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1_=tklabel(Saisi_,text="p1",font=PoliceGenerale)
Tp2_=tklabel(Saisi_,text="p2",font=PoliceGenerale)
alpha_<-tkentry(Saisi_, width=7)
p1_<-tkentry(Saisi_, width=7);p2_<-tkentry(Saisi_, width=7)
tkgrid(Tp1_, row=10, column=0, sticky="w")
tkgrid(p1_, row=10, column=1, sticky="w")
tkgrid(Tp2_, row=10, column=2, sticky="w")
tkgrid(p2_, row=10, column=3, sticky="w")
tkgrid(Talpha_, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha_, row=11, column=2, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0, 0.5]",font=PoliceGenerale)
point_<-tkentry(Saisi_, width=10)
tkgrid(Tpoint_, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point_, row=12, column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ;
const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1_, row=12, column=4, sticky="w")
tkgrid(const2_, row=13,column=4, sticky="w")
Twind_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
Wind_<-tkentry(Saisi_, width=10)
tkgrid(Twind_, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind_, row=13,column=1, sticky="w")
Tparr_<-tklabel(Saisi_, text="Mean inter-patient arrival time",font=PoliceGenerale)
Parr_<-tkentry(Saisi_, width=10)
tkgrid(Tparr_, row=14,column=0,columnspan=3, sticky="w")
tkgrid(Parr_, row=14,column=2, sticky="w")
Tacc_<-tklabel(Saisi_, text="Accrual",font=PoliceGenerale)
Acc_<- tk2spinbox(Saisi_, values = c("fixed","poisson"),width=7)
tkgrid(Tacc_, row=15,column=0, sticky="w")
tkgrid(Acc_, row=15,column=1, sticky="w")
Ttox_<-tklabel(Saisi_, text="Time until toxicity occurence",font=PoliceGenerale)
tox_<- tk2spinbox(Saisi_, values = c("uniform","exponential"), width=10)
tkgrid(Ttox_, row=16,column=0,columnspan=3, sticky="w")
tkgrid(tox_, row=16,column=2, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=17,column=0,columnspan=2, sticky="w")
tkgrid(Seed_, row=17,column=2, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=18,column=0, sticky="w")
tkgrid(names.S_, row=18,column=1,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
tclArrayVar <- function(Rarray=NULL)
{
if (!is.null(Rarray) && !is.vector(Rarray) && length(dim(Rarray))!=2)
stop("Array must be one-dimensional or two-dimensional.")
n <- .TkRoot$env$TclVarCount <- .TkRoot$env$TclVarCount +1L
name <- paste("::RTcl", n,sep = "")
l <- list(env = new.env(),nrow=0,ncol=0,ndim=0)
assign(name, NULL, envir = l$env)
reg.finalizer(l$env, function(env) tcl("unset", ls(env)))
class(l) <- "tclArrayVar"
if (is.null(Rarray))
{
ndim <- 2
.Tcl(paste("set ",name,"(0,0) \"\"",sep=""))
}
else
{
if (is.vector(Rarray))
{
ndim <- 1
Rarray <- as.data.frame(Rarray)
}
else
ndim <- 2
for (i in (1:nrow(Rarray)))
if (ndim==2)
for (j in (1:ncol(Rarray)))
.Tcl(paste("set ",name,"(",i,",",j,") \"",paste(Rarray[i,j]),"\"",sep=""))
else
.Tcl(paste("set ",name,"(",i,",",1,") \"",paste(Rarray[i,1]),"\"",sep=""))
if (!is.null(rownames(Rarray)))
for (i in (1:nrow(Rarray)))
.Tcl(paste("set ",name,"(",i,",",0,") \"",rownames(Rarray)[i],"\"",sep=""))
else
for (i in (1:nrow(Rarray)))
.Tcl(paste("set ",name,"(",i,",",0,") \"\"",sep=""))
if (!is.null(colnames(Rarray)))
for (j in (1:ncol(Rarray)))
.Tcl(paste("set ",name,"(",0,",",j,") \"",colnames(Rarray)[j],"\"",sep=""))
else
for (j in (1:ncol(Rarray)))
.Tcl(paste("set ",name,"(",0,",",j,") \"\"",sep=""))
l$nrow <- nrow(Rarray)
l$ncol <- ncol(Rarray)
}
l$ndim <- ndim
l
}
print.tclArrayVar <- function(tclArray,height=100,width=100)
{
tt <- tktoplevel()
tclRequire("Tktable")
tclArrayName <- ls(tclArray$env)
table1 <- tkwidget(tt,"table",rows=paste(tclArray$nrow+1),cols=paste(tclArray$ncol+1),colwidth=15,titlerows="1",titlecols="1",
height=paste(height+1),width=paste(width+1))
tkgrid(table1)
tkconfigure(table1,variable=tclArrayName,background="white")
tkconfigure(table1,resizeborders="col")
tkconfigure(table1,multiline="0")
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive TITE-EWOC or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Time-to-Event Escalade With Overdose Control Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://www.ncbi.nlm.nih.gov/pubmed/21351289", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit = function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_TEWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_TEWOC, "630x550")
tkwm.geometry(Win_TEWOC, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TEWOC, ilogo)
tktitle(Win_TEWOC) <- "GUI TEWOC"
tkpack.propagate(Win_TEWOC, FALSE)
topMenu <- tk2menu(Win_TEWOC)
tkconfigure(Win_TEWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-EWOC", command=NewTEWOC)
tkadd(newStudyMenu,"command", label="Tite-EWOC simulator", command=SimTEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_TEWOC); frameInit()} )
tkadd(AideMenu,"command", label="Help R (Publi)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TEWOC))
}
frameInitTEWOC = function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_TEWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_TEWOC, "595x600")
tkwm.geometry(Win_TEWOC, "+400+80")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TEWOC, ilogo)
tktitle(Win_TEWOC) <- "GUI TEWOC"
tkpack.propagate(Win_TEWOC, FALSE)
topMenu <- tk2menu(Win_TEWOC)
tkconfigure(Win_TEWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-EWOC", command=NewTEWOC)
tkadd(newStudyMenu,"command", label="Tite-EWOC simulator", command=SimTEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_TEWOC); frameInit()})
tkadd(AideMenu,"command", label="Help R (Publi)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TEWOC))
assign("net.TEWOC", tk2notebook(Win_TEWOC, tabs = c("Input parameters","Include","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TEWOC , fill = "both", expand = 1)
assign("Resultas", tk2notetab(net.TEWOC , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("include", tk2notetab(net.TEWOC , "Include"),envir = as.environment(pos))
tkpack.propagate(include, FALSE)
assign("Required", tk2notetab(net.TEWOC , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("Saisi", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Run", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run, FALSE)
assign("m2", tkframe(Required, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
}
frameInitSIM = function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_TEWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_TEWOC, "715x725")
tkwm.geometry(Win_TEWOC, "+400+80")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TEWOC, ilogo)
tktitle(Win_TEWOC) <- "GUI TEWOC"
tkpack.propagate(Win_TEWOC, FALSE)
topMenu <- tk2menu(Win_TEWOC)
tkconfigure(Win_TEWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-EWOC", command=NewTEWOC)
tkadd(newStudyMenu,"command", label="Tite-EWOC simulator", command=SimTEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_TEWOC); frameInit()})
tkadd(AideMenu,"command", label="Help R (Publi)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TEWOC))
assign("net.TEWOC_", tk2notebook(Win_TEWOC, tabs = c("Input parameters","Results")),envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TEWOC_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.TEWOC_ , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.TEWOC_ , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=0, columnspan=2, rowspan=7)
}
frameInit()
}
.ewocht<- function (a, x, y, w, p1, p2,law)
{
v=switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((((tanh(x[i])+1)/2)^a)^y[i]) * ((1 - w[i]*(((tanh(x[i])+1)/2)^a))^(1-y[i]))
}
return(v)
}
.ewochte<-function (a, x, y, w, p1, p2, law)
{
v=a*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((((tanh(x[i])+1)/2)^a)^y[i]) * ((1 - w[i]*(((tanh(x[i])+1)/2)^a))^(1-y[i]))
}
return(v)
}
.ewochtv<-function (a, x, y, w, p1, p2, law)
{
v=(a^2)*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((((tanh(x[i])+1)/2)^a)^y[i]) * ((1 - w[i]*(((tanh(x[i])+1)/2)^a))^(1-y[i]))
}
return(v)
}
.ewoclgt <-function (a, x, y, w, p1, p2, cst, law)
{
v=switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * (plogis(cst+a*x[i])^y[i]) *
((1-w[i]*plogis(cst+a*x[i]))^(1-y[i]))
}
return(v)
}
.ewoclgte <-function (a, x, y, w, p1, p2, cst, law)
{
v=a*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * (plogis(cst+a*x[i])^y[i]) *
((1-w[i]*plogis(cst+a*x[i]))^(1-y[i]))
}
return(v)
}
.ewoclgtv <-function (a, x, y, w, p1, p2, cst, law)
{
v=(a^2)*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * (plogis(cst+a*x[i])^y[i]) *
((1-w[i]*plogis(cst+a*x[i]))^(1-y[i]))
}
return(v)
}
.ewocpw <-function (a, x, y, w, p1, p2, law)
{
v=switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((x[i]^a)^y[i]) * ((1-w[i]*(x[i]^a))^(1-y[i]))
}
return(v)
}
.ewocpwe <-function (a, x, y, w, p1, p2, law)
{
v=a*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((x[i]^a)^y[i]) * ((1-w[i]*(x[i]^a))^(1-y[i]))
}
return(v)
}
.ewocpwv <-function (a, x, y, w, p1, p2, law)
{
v=(a^2)*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((x[i]^a)^y[i]) * ((1-w[i]*(x[i]^a))^(1-y[i]))
}
return(v)
}
.HTGamma<-function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow((exp(d[i])/(exp(d[i]) + exp(-d[i]))), alpha)
}
alpha ~ dgamma(p1, 1/p2)
}
.PowerGamma<-function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow(d[i], alpha)
}
alpha ~ dgamma(p1, 1/p2)
}
.LogisticGamma<-function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*ilogit(intcpt + alpha * d[i])
}
alpha ~ dgamma(p1, 1/p2)
}
.HTUnif <- function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow((exp(d[i])/(exp(d[i]) + exp(-d[i]))), alpha)
}
alpha ~ dunif(p1, p2)
}
.LogisticUnif <- function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*ilogit(intcpt + alpha * d[i])
}
alpha ~ dunif(p1, p2)
}
.PowerUnif <- function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow(d[i], alpha)
}
alpha ~ dunif(p1, p2)
}
.titeewoc <- function(prior, target, dose=NULL, tox=NULL, level, n = length(level), weights = NULL, followup = NULL,
obswin = NULL, method = "exact", model = "ht", constrain = TRUE, pointest="plugin", p.dist="unif",
p1 = ifelse(p.dist == "gamma", 2, 0), p2=ifelse(p.dist == "gamma", 0.7, 5), alphap=1,
intcpt = 3, seed=NULL, burnin.itr = 2000, production.itr = 2000)
{
if (is.null(weights)) {
if (!(is.null(followup) | is.null(obswin))) {
weights <- followup/obswin
} else {
stop("Cannot define weigths, check followup and obswin")
}
} else { weigths <- pmin(weights, 1)}
if (any(weights > 1) | any(weights < 0))
stop(" Weights have to be between 0 and 1!")
if (!is.null(dose)) {
if (!(length(dose) == length(prior)))
stop(" Prior and dose must be of same lengths")
}
if (!(length(tox) == length(level) & length(tox) == length(weights)))
stop(" tox, level, and weights must be of same lengths!")
if (missing(prior))
stop(" Prior proabilities are missing")
if (any(prior > 1) | any(prior < 0))
stop(" Prior probabilities have to be between 0 and 1!")
if ((target > 1) | (target < 0))
stop(" Target has to be between 0 and 1!")
if ((!model %in% c("ht", "logit1", "power")))
stop("model must be one of 'ht', 'logit1', 'power'")
if ((!p.dist %in% c("unif", "gamma")))
stop("Prior distribution must be one of 'unif', 'gamma'")
if ((p.dist == "unif")& (p2<=p1))
stop("invalid parameters p1 and p2")
if ((!method %in% c("exact", "rjags")))
stop ("unknown estimation method")
if (!((pointest=="plugin")|((pointest <= 0.5)&(pointest > 0))))
stop ("Pointest must be equal to 'plugin' or between ]0,0.5]")
if (!(pointest=="plugin")&(method=="exact"))
warning("Only pointest equals to plugin is available for exact method")
if (!is.null(seed))
set.seed(seed)
if (missing(level))
stop(" Level is missing")
weights[tox == 1] <- 1
y1p <- tox
w1p <- weights
k <- length(prior)
nb.pat.level <- rep(0,k)
nb.tox.level <- rep(0,k)
weights.level<- rep(0,k)
for (i in 1:k){
nb.pat.level[i]<-table(factor(level, levels = 1:k))[[i]]
nb.tox.level[i]<-xtabs(tox~factor(level, levels = 1:k))[[i]]
weights.level[i]<-xtabs(w1p~factor(level, levels = 1:k))[[i]]}
inzero=which(nb.pat.level!=0)
weights.level[inzero] <- weights.level[inzero]/nb.pat.level[inzero]
if (method == "exact") {
if (model == "ht") {
dosescaled <- atanh(2*prior^(1/alphap)-1)
x1p <- dosescaled[level]
f.model <-function(dose, alpha,cst) {
((tanh(dose) + 1)/2)^alpha}
cst.den <- integrate(.ewocht, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]
est <- integrate(.ewochte, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den
cdf <- function(aU){ integrate(.ewocht, 0, aU, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den}
ptox <- f.model(dosescaled,est,1)
mtd. <- atanh(2*target^(1/est)-1)
}
if (model == "logit1") {
dosescaled <- (qlogis(prior) - intcpt)/alphap
x1p <- dosescaled[level]
f.model <- function(dose, alpha,cst) {plogis(cst+alpha*dose)}
cst.den <- integrate(.ewoclgt, 0, Inf, x1p, y1p, w1p, p1, p2,
intcpt, p.dist, abs.tol = 0)[[1]]
est <- integrate(.ewoclgte, 0, Inf, x1p, y1p, w1p, p1, p2,
intcpt, p.dist, abs.tol = 0)[[1]]/cst.den
cdf <- function(aU){ integrate(.ewoclgt, 0, aU, x1p, y1p, w1p, p1, p2,
intcpt, p.dist, abs.tol = 0)[[1]]/cst.den}
ptox <- f.model(dosescaled,est,intcpt)
mtd. <- (log(target/(1 - target)) - intcpt)/est
}
if (model == "power") {
dosescaled <- prior^(1/alphap)
x1p <- dosescaled[level]
f.model <- function(dose, alpha, cst) {dose^alpha}
cst.den <- integrate(.ewocpw, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]
est <- integrate(.ewocpwe, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den
cdf <- function(aU){integrate(.ewocpw, 0, aU, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den}
ptox <- f.model(dosescaled,est,1)
mtd. <- target^(1/est)
}
fn <- function(aU_, q) {abs(cdf(aU_) - q)}
alpha.quantiles <- sapply(c(0.025, 0.25, 0.5, 0.75, 0.975),
function(q) {
max.x <- seq(0, 10*est, length = 100)[which.min(sapply(seq(0,
10*est, length = 100), function(i) {
fn(i, q)
}))]
if(max.x==0){max.x <-0.001}
optimize(fn, c(0, max.x), q = q, tol = .Machine$double.eps^0.5)$minimum
})
quantiles <- sapply(dosescaled, function(d) {
f.model(d, sort(alpha.quantiles, TRUE),intcpt)
})
alpha.quantiles<- matrix(alpha.quantiles,nrow=1,ncol=5)
rownames(quantiles) <- colnames(alpha.quantiles) <-
c("2.5%", "25%", "50%", "75%", "97.5%")
current <- level[length(level)]
if (all(ptox <= target)) {
dose.rec <- k
} else if (all(ptox >= target)) {
dose.rec <- 1
} else {
dose.rec <- if (!constrain) {
which.min(abs(ptox - target))
}else {
which.min(abs(ptox[1:min(current + 1, k)] - target))
}
}
results <- list(dose.rec = dose.rec, alpha.est = est, alpha.quantiles=alpha.quantiles,
post.ptox=ptox,quantiles.ptox = quantiles, prior=prior, target=target, model=model,
method=method, prior.alpha=list(dist=p.dist,p1=p1,p2=p2), sdose=dosescaled,
constrain=constrain, pointest=pointest, nb.pat.level=nb.pat.level,
nb.tox.level=nb.tox.level, weights.m.level=weights.level)
}else{
if (model == "ht"){
model.file <- switch(p.dist,gamma=.HTGamma, unif=.HTUnif)
f.dose<- function(alpha,ptox, cst) atanh(2*ptox^(1/alpha)-1)
f.model <- function(dose, alpha,cst) {
((tanh(dose) + 1)/2)^alpha}
dosescaled <- f.dose(alphap, prior, intcpt)
} else if (model == "logit1") {
model.file <- switch(p.dist,gamma=.LogisticGamma, unif=.LogisticUnif)
f.dose<- function(alpha,ptox, cst)(qlogis(ptox) - cst)/alpha
f.model <- function(dose, alpha,cst) {plogis(cst+alpha*dose)}
dosescaled <- f.dose(alphap,prior,intcpt)
} else {
model.file <- switch(p.dist,gamma=.PowerGamma, unif=.PowerUnif)
f.dose <- function(alpha,ptox, cst) ptox^(1/alpha)
f.model <- function(dose, alpha, cst) {dose^alpha}
dosescaled <- f.dose(alphap,prior,intcpt)
}
if (model == "logit1"){
mydata <- list(N1 = k, s = nb.tox.level, w=weights.level, d = dosescaled, p1 = p1,
p2 = p2, intcpt=intcpt, n=nb.pat.level)
}else {mydata <- list(N1 = k, s = nb.tox.level, w=weights.level, d = dosescaled,
p1 = p1, p2 = p2, n=nb.pat.level) }
path.model <- file.path(tempdir(), "model.file.txt")
R2WinBUGS::write.model(model.file, path.model)
r.init <- switch(p.dist,gamma=rgamma(1,shape=p1,scale=p2),unif=runif(1, p1, p2))
inits.list <- list(list(alpha = 1, .RNG.seed = sample(1:1e+06, size = 1),
.RNG.name = "base::Wichmann-Hill"),
list(alpha = r.init, .RNG.seed = sample(1:1e+06, size = 1), .RNG.name = "base::Wichmann-Hill"))
jagsobj <- rjags::jags.model(path.model, data = mydata, n.chains = 2,
quiet = TRUE, inits = inits.list)
update(jagsobj, n.iter = burnin.itr, progress.bar = "none")
j.samples <- rjags::jags.samples(jagsobj, "alpha", n.iter = production.itr/2,
progress.bar = "none")
alpha.samples <- c(j.samples$alpha)
alpha.quantiles<-apply(as.matrix(alpha.samples),2,quantile, c(0.025, 0.25, 0.5,
0.75, 0.975))
samples.ptox <- sapply(dosescaled, function(d) {
f.model(d, alpha.samples, intcpt)})
quantiles <- apply(samples.ptox, 2, quantile, c(0.025, 0.25,
0.5, 0.75, 0.975))
mean.alpha <- apply(as.matrix(alpha.samples), 2, mean)
if (pointest=="plugin") {
ptox <- sapply(dosescaled, function(d) {
f.model(d, mean.alpha,intcpt)
})
} else { ptox <- NA}
if (pointest!= "plugin") {
mtd <- f.dose(alpha=alpha.samples,ptox = target,cst=intcpt)
target.mtd <- quantile(mtd, pointest)
}
current <- level[length(level)]
dose.rec <- if (pointest == "plugin") {
if (!constrain) {
which.min(abs(ptox - target))
}else {
which.min(abs(ptox[1:min(current + 1, k)] - target))
}
} else { if (!constrain) {
which.min(abs(dosescaled - target.mtd))
}else {
which.min(abs(dosescaled[1:min(current + 1, k)] - target.mtd))
}
}
results<-list(dose.rec = dose.rec, alpha.mean = mean.alpha, alpha.quantiles=alpha.quantiles,
post.ptox=ptox, quantiles.ptox = quantiles, prior=prior, target=target, model=model, mtd.est=target.mtd,
method=method, prior.alpha=list(dist=p.dist,p1=p1,p2=p2), sdose=dosescaled, constrain=constrain,
pointest=pointest, nb.pat.level=nb.pat.level, nb.tox.level=nb.tox.level,
weights.m.level=weights.level)
}
class(results) <- "Tite-Ewoc"
return (results)
}
.titeewocsim <- function(nsim, true, prior, target, dose=NULL, accrual = "fixed", obswin = NULL, tparr = obswin,
start = 1, samplesize, method = "exact", pointest=0.25, model = "ht", toxocc="unif",
p.dist="unif", alphap = 1, p1 = ifelse(p.dist == "gamma", 2, 0),
p2=ifelse(p.dist == "gamma", 0.7, 1), intcpt = 3, rateexp=1/obswin,
constrain = TRUE, count =FALSE, seed=NULL, burnin.itr = 2000, production.itr = 2000)
{
if (missing(nsim))
stop(" Number of simulations is missing")
if (is.null(obswin))
stop("Observation window must be defined")
if (missing(prior))
stop(" Prior proabilities are missing")
if (any(prior > 1) | any(prior < 0))
stop(" Prior probabilities have to be between 0 and 1!")
if (missing(true))
stop(" True proabilities are missing")
if (any(true > 1) | any(true < 0))
stop(" True probabilities have to be between 0 and 1!")
if ((target > 1) | (target < 0))
stop(" Target has to be between 0 and 1!")
if ((!model %in% c("ht", "logit1", "power", "logit2")))
stop("model must be one of 'ht', 'logit1', 'power' or 'logit2'")
if ((!method %in% c("exact", "rjags")))
stop ("unknown estimation method")
if ((!accrual %in% c("fixed", "poisson")))
stop ("unknown patient accrual scheme")
if ((!toxocc %in% c("unif", "exp")))
stop ("unknown distribution for time-to-toxicity")
if (!((pointest=="plugin")|((pointest <= 0.5)&(pointest > 0))))
stop ("Pointest must be equal to 'plugin' or between ]0,0.5]")
if (!(pointest=="plugin")&(method=="exact"))
warning("Only pointest equals to plugin is available for exact method")
if (!is.null(seed))
set.seed(seed)
if (missing(samplesize))
stop(" Sample size is missing")
if (!is.null(dose)) {
if (!(length(dose) == length(prior)))
stop("Prior and dose must be of same lengths")
if (start > (length(prior)))
start <- min(which(start == dose))
}
if (!(length(prior) == length(true)))
stop("Prior and true probabilities must be of same lengths")
if (length(start) > 1)
stop("Start must be a single value")
k <- length(prior)
dose.rec <- DURATION <- rep(NA, nsim)
alphaDist <- rep(NA, nsim)
nb.pat.level <- matrix(NA,nrow=nsim,ncol=k)
nb.tox.level <- matrix(NA,nrow=nsim,ncol=k)
dose.rec.level <- numeric(k)
sim <- 1
for (sim in 1:nsim) {
if (count) {
cat("simulation number:", sim, "\n")
}
if (accrual == "fixed") {
next.arrival <- rep(tparr,samplesize)
}else if (accrual == "poisson") {
next.arrival <- rpois(samplesize, tparr)
}
level <- rep(NA,samplesize)
level[1] <- start
w <- y <- followuppat <- numeric(samplesize)
if (toxocc == "unif")
TItox <- round(runif(samplesize, 0, obswin))
if (toxocc == "exp")
TItox <- pmin(round(rexp(samplesize, rate=rateexp)),obswin)
ttox <- t(matrix(rbinom(samplesize*k, 1, true),k,samplesize))
for (i in 1:samplesize)
{
y[i] <- ttox[i,level[i]]
if (y[i]==1) {
followuppat[i] <- TItox[i]
w[i] <- 1}
for (j in 1:i) {
if (y[j]==0){followuppat[j] <- min(followuppat[j]+ next.arrival[i],obswin)
w[j]<-followuppat[j]/obswin }
}
w <- pmin(w,1)
obj<-.titeewoc(prior=prior,target=target, dose=dose, obswin=obswin, tox=y[1:i],level=level[1:i], n = i,
weights = w[1:i], method = method, model = model, constrain = constrain, pointest=pointest,
p.dist=p.dist, p1 = p1, p2 = p2, intcpt = intcpt, alphap=alphap,
burnin.itr = burnin.itr, production.itr = production.itr)
if (i < samplesize)
level[i+1]<-obj$dose.rec
}
level.pat<-table(factor(level, levels = 1:k))
level.tox<-xtabs(y~factor(level, levels = 1:k))
for (l in 1:k){
nb.pat.level[sim,l]<-level.pat[[l]]
nb.tox.level[sim,l]<-level.tox[[l]]
}
dose.rec[sim] <- obj$dose.rec
DURATION[sim] <- sum(next.arrival[1:(samplesize-1)])+followuppat[samplesize]
if (method == "exact") {
alphaDist[sim] <-obj$alpha.est
} else {
if (model == "logit2"){
alphaDist[sim,] <-obj$alpha.mean}
else { alphaDist[sim] <-obj$alpha.mean }
}
}
for (l in 1:k){
dose.rec.level[l]<-table(factor(dose.rec, levels = 1:k))[[l]]}
dose.rec.level<-dose.rec.level/nsim*100
sim.results<-list(pct.dose.rec = dose.rec.level, prior=prior, true=true,
target=target, pat.level=colMeans(nb.pat.level), nb.tox.level=colSums(nb.tox.level),
duration=DURATION, alphaDist = alphaDist, method=method, samplesize=samplesize,
nsim=nsim, start=start, model=model)
class(sim.results) <- "Tite-Ewoc.Sim"
return (sim.results)
}
.print.titeewoc <- function(x)
{
cat(" Estimation method: ", x$method, "\n")
model.txt <- switch(x$model, ht = "Hyperbolic Tangent", logit1 = "1-parameter logistic",
power = "1-parameter power", logit2 = "Two-parameter logistic")
cat("\n Model: ", model.txt, "\n")
if (!(x$model == "logit2")) {
cat("\n Prior.alpha:", x$prior.alpha[1],"", "Param1:", x$prior.alpha[2],
"Param2:", x$prior.alpha[3], "\n")
}
dose.txt <- x$sdose
cat("\n Standardised doses : \n")
print(dose.txt)
if (x$constrain) {
cat("\n Modified (constrained) CRM used, starting dose level: ", "\n")
} else {
cat("\n Unmodified (unconstrained) CRM used \n")
}
if (x$pointest == "plugin") {
cat("\n Plug-in estimate of probability of toxicity used to select next dose \n")
} else {
cat("\n", 100 * x$pointest, "percentile of (standardised) MTD distribution used to select next dose",
"\n", 100 * x$pointest, "percentile is:", x$mtd.est,"\n")
}
tab <- rbind(x$nb.pat.level, x$nb.tox.level)
rownames(tab) <- c("n_Patient", "n_Tox")
colnames(tab) <- c(1:length(x$nb.tox.level))
colnames(tab) <- paste0("dose_",colnames(tab))
cat("\n Toxicities observed: \n")
print(tab)
tab2 <- signif(x$quantiles.ptox,3)
colnames(tab2) <- colnames(tab)
cat("\n Quantiles of posterior estimates of toxicity:: \n")
print(tab2)
cat("\n Next recommended dose level: ", x$dose.rec, "\n")
}
.print.titeewoc.sim <- function(x)
{
cat("Operating characteristics based on", x$nsim , "simulations: ", "\n")
cat("Starting dose level:", x$start , "\n")
cat("Sample size:", x$samplesize, "\n")
model.txt <- switch(x$model, ht = "Hyperbolic Tangent", logit1 = "1-parameter logistic",
power = "1-parameter power", logit2 = "Two-parameter logistic")
cat("\n Model: ", model.txt, "\n")
cat("\n Average study duration (mean [min,max]): ",
mean(x$duration),"[",min(x$duration),",", max(x$duration),"]", "\n")
tab <- signif(rbind(x$pct.dose.rec,x$pat.level),2)
rownames(tab) <- c("Recommended dose pourcentage", "Proportion of patients treated")
colnames(tab) <- c(1:length(x$pat.level))
colnames(tab) <- paste0("dose_",colnames(tab))
print(tab)
}
.plot.titeewoc <- function(x)
{
if (class(x)=="Tite-Ewoc") {
probs=t(x$quantiles.ptox)
plot.data = data.frame(
y2.5 = probs[,1],
y25 = probs[,2],
y50 = probs[,3],
y75 = probs[,4],
y97.5 = probs[,5],
dose.level=c(1:dim(x$quantiles.ptox)[2]),
target=x$target)
plot.data$dose.level=factor(plot.data$dose.level)
p <-ggplot2::ggplot(plot.data, aes(x=dose.level)) +
ggplot2::geom_boxplot(
aes(ymin = y2.5, lower = y25, middle = y50, upper = y75, ymax = y97.5,
color=dose.level),
stat = "identity"
) + ggplot2::ggtitle("Posterior p(DLT) quantiles: 2.5%, 25%, 50%, 75%, 97.5%") +
ggplot2::geom_hline(aes(yintercept = target),data = plot.data, col = 4, linetype = 2)
return(p)
} else {stop (" Plot defined only for Tite-Ewoc object") }
}
GUIP1 <- function()
{
e <- new.env()
welcome = function()
{
PoliceGenerale <- tkfont.create(family="calibri",underline=FALSE, size=14)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=20)
e$Win_GUIP1=tktoplevel(background = "light steel blue")
tkwm.geometry(e$Win_GUIP1, "765x450")
tkwm.geometry(e$Win_GUIP1, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(e$Win_GUIP1, ilogo)
tktitle(e$Win_GUIP1) <- "GUIP1"
tkpack.propagate(e$Win_GUIP1, FALSE)
e$wlc <- tkframe(e$Win_GUIP1,relief="groove",borderwidth=3)
tkpack.propagate(e$wlc, FALSE)
tkgrid(e$wlc, row=0, column=0, sticky="se")
tkgrid(tklabel(e$wlc, text="Welcome to GUIP1",font=PoliceTitre), row=0,columnspan=1, column=2 )
tkgrid(tklabel(e$wlc, text=" "), row=1, column=0)
tkgrid(tklabel(e$wlc, text="To start select one of the following model-guided adaptive designs",font=PoliceGenerale),
row=2, column=1,columnspan=3)
tkgrid(tklabel(e$wlc, text="
"), row=3, column=0)
CRMBbut=tkbutton(e$wlc, text="Bayesian-CRM", width=20, command=function(){dis.welcome();.CRMB(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMBbut, row=4, column=1)
CRMLbut=tkbutton(e$wlc,text="CRM-Likelihood",width=20,command=function(){dis.welcome();.CRML(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMLbut, row=4, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=5, column=0)
TITECRMbut=tkbutton(e$wlc,text="TITE-CRM", width=20, command=function(){dis.welcome();.TITECRM(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITECRMbut, row=6, column=2)
tkgrid(tklabel(e$wlc, text="
"), row=7, column=0)
EWOCbut=tkbutton(e$wlc,text="EWOC", width=20, command=function(){dis.welcome();.EWOC(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(EWOCbut, row=8, column=1)
TITEEWOCbut=tkbutton(e$wlc,text="TITE-EWOC", width=20, command=function(){dis.welcome();.TEWOC(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITEEWOCbut, row=8, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=9, column=4)
}
dis.welcome = function()
{
tkdestroy(e$Win_GUIP1)
PoliceGenerale<- tkfont.create(family="calibri",underline=FALSE, size=14)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=20)
e$Win_GUIP1=tktoplevel(background = "light steel blue")
tkwm.geometry(e$Win_GUIP1, "765x459")
tkwm.geometry(e$Win_GUIP1, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(e$Win_GUIP1, ilogo)
tktitle(e$Win_GUIP1) <- "GUIP1"
tkpack.propagate(e$Win_GUIP1, FALSE)
e$wlc <- tkframe(e$Win_GUIP1,relief="groove",borderwidth=3)
tkpack.propagate(e$wlc, FALSE)
tkgrid(e$wlc, row=0, column=0, sticky="se")
tkgrid(tklabel(e$wlc, text="Welcome to GUIP1",font=PoliceTitre), row=0,columnspan=1, column=2 )
tkgrid(tklabel(e$wlc, text=" "), row=1, column=0)
tkgrid(tklabel(e$wlc, text="To launch a new model-guided adaptive design, please close ongoing
study and press refresh button",font=PoliceGenerale),
row=2, column=1,columnspan=3)
tkgrid(tklabel(e$wlc, text="
"), row=3, column=0)
CRMBbut=tkbutton(e$wlc, text="Bayesian-CRM", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMBbut, row=4, column=1)
CRMLbut=tkbutton(e$wlc,text="CRM-Likelihood",width=20,state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMLbut, row=4, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=5, column=0)
TITECRMbut=tkbutton(e$wlc,text="TITE-CRM", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITECRMbut, row=6, column=2)
tkgrid(tklabel(e$wlc, text="
"), row=7, column=0)
EWOCbut=tkbutton(e$wlc,text="EWOC", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(EWOCbut, row=8, column=1)
TITEEWOCbut=tkbutton(e$wlc,text="TITE-EWOC", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITEEWOCbut, row=8, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=9, column=4)
TITECRMbut=tkbutton(e$wlc,text="Refresh", width=11, command=function(){tkdestroy(e$Win_GUIP1);GUIP1()}, bg="yellow", font=PoliceGenerale)
tkgrid(TITECRMbut, row=10, column=2)
}
welcome()
}
ddinart/GUIP1 documentation built on Nov. 4, 2019, 10:21 a.m.
R Package Documentation
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Defines functions .CRMB .CRML .TITECRM .EWOC .TEWOC .titeewoc .titeewocsim .print.titeewoc .print.titeewoc.sim .plot.titeewoc GUIP1
Documented in GUIP1
.CRMB=function(pos=1, e)
{
e$CRM.2 = NULL
e$ResSim = NULL
tclRequire("Tktable")
remplireRequid=function()
{
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
Model=as.numeric(tclvalue((rbValue.M)))
if (Model==1){Model.n="logistic"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (Model==2){Model.n="empiric"; intcpt=NULL}
Stop=as.numeric(tclvalue(rbValue.SC))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
assign("names_Study", tclvalue(tkget(names.S)), envir = as.environment(pos))
assign("Study",list(name=paste(names_Study) ,Nb_Dl=Nb_Dl, DL=DL, Target=Target, Model=Model, Model.n=Model.n,
Stop=Stop, N_Pat=N_Pat ,N_pat_Level=N_pat_Level, halfwidthPrior=halfwidthPrior,
nuPrior=nuPrior, Intcpt=intcptPrior, Sd=sdPrior), envir = as.environment(pos))
differ=abs(Study$DL-Study$Target)
MTD=1
for ( i in 1 : Study$Nb_Dl)
{
if (differ[i]==min(differ))
{MTD=i}
}
Pat_include=0
PT.data=NULL
assign("Res",list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data), envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
assign("a00", paste(names_Study), envir = as.environment(pos))
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'crmb', sep='.'))
}
Study.file()
tk2notetab.select(net.CRMB , "Include")
}
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
tk2notetab.select(net.CRMB , "Input parameters")
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses<- nlevel
priorProbaf <- c()
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (tkget(eval(parse(text = paste('valp',i,sep='')))))
priorProbaf <- c(priorProbaf,as.numeric(tclvalue(n.iter)))
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter, state="disabled"),envir = as.environment(pos)),sticky="w",row=r,column=1)
}
if (any(priorProbaf <= 0) | any(priorProbaf >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(priorProbaf, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
SliderValue=tclVar(nlevel)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue,state="disabled",
resolution=1, orient="horiz")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(TargetPrior)
Target<-tkentry(Saisi, width=5,textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi) ; rb2.1 <- tkradiobutton(Saisi)
rbValue.M <- tclVar(modelPrior)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic", state="disabled", font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric", state="disabled", font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(sdPrior)
sd.<-tkentry(Saisi,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=8,column=0, sticky="w")
tkgrid(sd., row=8,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(intcptPrior)
}else {tclVar("NA")}
assign("intcpt.",tkentry(Saisi, textvariable=n.iter, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=8,column=2, sticky="w")
tkgrid(intcpt., row=8,column=3, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam<- tclVar()
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
assign("etatPrior",TRUE,envir = as.environment(pos))
}
disabled.PriorCalib=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
if(is.tkwin(SaisiCal)){tkdestroy(SaisiCal)}
if(is.tkwin(Saisi.saveCal )){tkdestroy(Saisi.saveCal )}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar(Study$Nb_Dl)
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
for ( i in 1:Study$Nb_Dl)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar (tkget(eval(parse(text = paste('val',i,sep='')))))
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCAL,text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCAL,state="disabled", width=8,textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
if(Study$Nb_Dl!=8)
{
for ( i in (Study$Nb_Dl+1):8)
{
r=10 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
n.iter=tclVar(round(TargetPrior,3))
Target.cal<-tkentry(SaisiCal,textvariable=n.iter,state="disabled", width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
n.iter=tclVar(halfwidthPrior)
halfwidth<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal,state="disabled") ; rb2.1CAL <- tkradiobutton(SaisiCal,state="disabled")
assign("rbValue.MCAL", tclVar(modelPrior), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
n.iter=tclVar(nuPrior)
nu<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_nu, row=6,column=0, sticky="w")
tkgrid(nu, row=6,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
n.iter=tclVar(Study$Sd)
sd.<-tkentry(SaisiCal,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=7,column=0, sticky="w")
tkgrid(sd., row=7,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(Study$Intcpt)}
else {tclVar("NA")}
assign("intcpt.", tkentry(SaisiCal, textvariable=n.iter, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,bg="cornflower blue",state="disabled")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,bg="cornflower blue",state="disabled")
tkgrid(Validation, row=2)
}
PriorCalib=function(...)
{
.Crea.f.CAL=function(...)
{
assign("TargetPrior", as.numeric(tclvalue(tkget((Target.cal)))), envir = as.environment(pos))
assign("halfwidthPrior", as.numeric(tclvalue(tkget((halfwidth)))), envir = as.environment(pos))
assign("nuPrior", as.numeric(tclvalue(tkget(nu))), envir = as.environment(pos))
assign("nlevel", as.numeric(tclvalue(tkget((slider_Nb_DL.CAL)))), envir = as.environment(pos))
assign("modelPrior", as.numeric(tclvalue(((rbValue.MCAL)))), envir = as.environment(pos))
assign("sdPrior", as.numeric(tclvalue(tkget((sd.)))), envir = as.environment(pos))
assign("intcptPrior", as.numeric(tclvalue(tkget((intcpt.)))), envir = as.environment(pos))
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
if (TargetPrior>0.55) cat("\n Warning: Target DLT rate too high")
if (TargetPrior<0.15) cat("\n Warning: Target DLT rate too low")
if ((halfwidthPrior<=0)|(halfwidthPrior>0.5)) stop('Halfwidth of the indifference intervals incorrect!')
if ((halfwidthPrior<=0.5)&(halfwidthPrior>0.2)) cat("\n Warning: Try to reduce the value of the halfwidth of the indifference intervals ")
if ((nuPrior<1)|(nuPrior>Nb_Niv_DosesCAL)|(nuPrior%%1 != 0)) stop(paste('Prior guess of MTD incorrect, enter an integer between 1 and',Nb_Niv_DosesCAL))
if (modelPrior==1)
{
e$prior<-dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel, model="logistic", intcpt=intcptPrior)
}
if (modelPrior==2)
{
e$prior<-dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel, model="empiric")
}
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(round(e$prior[i],3))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,textvariable=n.iter),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_DosesCAL!=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
f.CALPrior=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("affCAL",tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8), envir = as.environment(pos)),row=r,column=1)
}
if(Nb_Niv_DosesCAL !=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Param.choice = function(...)
{
if (as.numeric(tclvalue((rbValue.MCAL)))==2)
{
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(SaisiCal, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar('8')
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",command=f.CALPrior)
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
Target.cal<-tkentry(SaisiCal, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
halfwidth<-tkentry(SaisiCal, width=10)
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
rb2.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
rbValue.MCAL <- tclVar(1)
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
sd.<-tkentry(SaisiCal, width=10)
tkgrid(Tsd., row=4,column=2, sticky="w")
tkgrid(sd., row=4,column=3, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
nu<-tkentry(SaisiCal, width=10)
tkgrid(lab_nu, row=7,column=0, sticky="w")
tkgrid(nu, row=7,column=1, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,command=.Crea.f.CAL,bg="cornflower blue")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,command=remplireRequid,bg="cornflower blue")
tkgrid(Validation, row=2)
}
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.crmb or file.cbsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
if (extension == "crmb") {
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$CRM.2 <- CRM.2
Open.CRM()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
}
}
if (extension == "bsim") {
load(file =paste(paste(names_Study,'cbsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS",StudyS, envir = as.environment(pos))
tkdestroy(Win_CRMB)
frameInitSIM()
disabled.SimCRM()
}
}
pending_listing=function()
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
dataa=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(dataa)==0 )
{
msg <- paste("No patient pending",sep="")
tkmessageBox(message=msg)
}
if (nrow(dataa)>=1)
{
assign("tt.pend", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(tt.pend, "+650+400")
assign("tl",tklistbox(tt.pend,height=4,selectmode="single",background="white"), envir = as.environment(pos))
tkgrid(tklabel(tt.pend,text="Select a patient",font=PoliceGenerale))
tkgrid(tl)
numPatP=paste("Patient N'", as.character(dataa$patid),sep="")
for (i in (1:length(numPatP)))
{
tkinsert(tl,"end",numPatP[i])
}
tkselection.set(tl,0)
OK.but <-tkbutton(tt.pend,text=" OK ",command=.include.pending,bg="cornflower blue")
tkgrid(OK.but)
tkfocus(tt.pend)
}
}
.include.pending <- function()
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
data.pinding=Res$PT.data[which(Res$PT.data$pndg==1),]
data.inclus=Res$PT.data[which(Res$PT.data$pndg==0),]
numPatP=as.character(data.pinding$patid)
assign("Choice", as.numeric(numPatP[as.numeric(tkcurselection(tl))+1]), envir = as.environment(pos))
print(Choice)
Inc=tktoplevel()
tkwm.geometry(Inc, "+650+400")
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
assign("Titre", tklabel(Inc.mm1,text="DLT",font=PoliceGenerale), envir = as.environment(pos))
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i))))
}
.Sauv2=function(...)
{
assign("DLT", as.numeric(tclvalue((rbValue.DLT))), envir = as.environment(pos))
Newpat=data.pinding[which(data.pinding$patid==Choice),]
Newpat$DLT=DLT
Newpat$pndg=0
DATA=rbind(data.inclus,Newpat)
e$CRM.2 <- dfcrm::crm( prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1],method = "bayes", conf.level = 0.95,
model = paste(Study$Model.n), scale=Study$Sd, intcpt=Study$Intcpt)
Res$MTD=e$CRM.2$mtd
Res$PT.data[which(Res$PT.data$patid==Choice),]$pndg=0
Res$PT.data[which(Res$PT.data$patid==Choice),]$DLT=DLT
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res",Res, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRMB", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRMB,text="Validate",width=30,command=.Sauv2,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRMB)
tkdestroy (tt.pend)
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-bayesian approach (CRMB) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRMB,text="New patient",width=30,command=.include,bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRMB,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRMB, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_CRMB)
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-bayesian approach (CRMB) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
print('CAS 1')
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRMB,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRMB,text="Pending patient",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.CRMB ,"Results")
print(' Fin CAS 1')
tkgrid(Rec.Win_CRMB, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
if (nrow(DATA)!=0)
{
print('CAS 2')
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRMB,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRMB,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRMB, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
print(' Fin CAS 2')
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2]),
envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for (i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,
total.tox=total.tox, ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="15",background="white")
tkgrid(t.d, row=2, column=0)
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2])
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,
total.tox=total.tox, ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
GrapheResults()
dev.off()
pdf(paste(paste(filef,"2",sep=""),"pdf",sep="."))
curvesIC()
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
setColWidths(wb, sheet2, cols=c(3,4), widths = 14.43)
setColWidths(wb, sheet2, cols=c(1,2,5,6,7), widths = 10.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:7,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphics",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Patient history",width=20,command=Export.Graph,bg="cornflower blue")
button3b=tkbutton(Resultas ,text="Dose-tox curves",width=20,command=Export.CurvesIC,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(button3b, row=5, column=3)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.include=function(...)
{
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
Inc<-tktoplevel()
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for ( i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
tkgrid(assign(paste('rDLT',2,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=2, text=paste("pending"))))
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))), envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))), envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1), envir = as.environment(pos))
assign("pndg", as.numeric (c(Res$PT.data[,4],as.numeric(tclvalue((rbValue.DLT)))==2)), envir = as.environment(pos))
Res$PT.data <- data.frame(DL=DL,DLT=DLT,patid=patid,pndg=pndg)
Res$Pat.included <- Res$Pat.included+1
print(Res$PT.data)
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
print(length(DATA)!=0)
if (nrow(DATA)!=0)
{
e$CRM.2<-dfcrm::crm(prior=Study$DL, target=Study$Target, tox=DATA[,2], level=DATA[,1], method = "bayes", conf.level = 0.95,
model = paste(Study$Model.n), scale=Study$Sd, intcpt=Study$Intcpt)
Res$MTD <- e$CRM.2$mtd
}
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'crmb',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRMB", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRMB,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRMB)
}
GrapheResults=function(...)
{
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
n=length(DATA[,1])
x=c(1:n)
y=DATA[,1]
z=DATA[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
Export.Graph=function()
{
GrapheResults()
}
curvesIC = function(...)
{
post.var <- e$CRM.2$post.var
crit <- qnorm(0.5 + e$CRM.2$conf.level/2)
doses=e$CRM.2$dosescaled
Fempi=function(doses,beta){doses^(exp(beta))}
Flogi=function(doses,beta){(1 + exp(-e$CRM.2$intcpt- exp(beta) * doses))^{-1}}
Fmodel <- switch(e$CRM.2$model,empiric=Fempi, logistic=Flogi)
plot(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),'l', lwd=2,xaxt="n",
ylim=c(0, 1),xlab="Dose level", ylab="Proba. of DLT")
axis(1, at = seq(1, length(e$CRM.2$prior), by = 1))
abline(h=e$CRM.2$target,col="blue",lty=2,lwd=2)
objtitle <-rbind("Dose-toxicity curve + 0.95_IC",paste(e$CRM.2$model, "model"))
title(main=objtitle)
legend('topright',c("Proba. of DLT", "IC(0.95)","target"),lty=c(1,1,2), col=c('black','red','blue'),lwd=2)
points(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),lwd=2)
if (post.var >= 0) {
lb <- e$CRM.2$estimate - crit * sqrt(post.var)
ub <- e$CRM.2$estimate + crit * sqrt(post.var)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,lb),col="red",lwd=2)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,ub),col="red",lwd=2)
}else{print('Confidence interval not calculated')}
}
Export.CurvesIC=function()
{
curvesIC()
}
NewCRM=function()
{
tkdestroy(Win_CRMB)
frameInitCRM()
PriorCalib()
}
disabled.CRM=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.CRM=function()
{
tkdestroy(Win_CRMB)
frameInitCRM()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=5, textvariable=n.iter,state="disabled"),) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(Study$Sd)
sd.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tsd., row=6,column=2, sticky="w")
tkgrid(sd., row=6,column=3, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
n.iter <- tclVar(Study$Intcpt)
intcpt.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
Titre=tklabel(Saisi,text="Names of study",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(Titre, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
WordExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
docx( ) %>%
addFlexTable(dframe %>%
FlexTable(header.cell.props = cellProperties( background.color = "#003366"),
header.text.props = textBold(color = "white"),
add.rownames = TRUE ) %>%
setZebraStyle(odd = "#DDDDDD", even = "#FFFFFF")) %>%
writeDoc(file = "ResExport.docx")
Save.word.infos <- tkmessageBox(title = "Word Export",
message = "File ResExport.docx saved in the current working directory of the R proces", icon = "info", type = "ok")
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00<-paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'cbsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'cbsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("bayesian approach (CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
disabled.SimCRM=function()
{
.RecapSimB=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00<-paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'cbsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'cbsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("bayesian approach (CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,command=function()ExcellExport(ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
Nb_Niv_Doses<- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
n_<-tkentry(Saisi_, width=5, textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,state="disabled") ; rb2.1_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Model == "logistic") {
rbValue.M_ <- tclVar(1)
n.intcpt <- tclVar(StudyS$Intcpt)}
if (StudyS$Model == "empiric") {
rbValue.M_ <- tclVar(2)
n.intcpt <- tclVar("NA")}
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation", font=PoliceGenerale)
n.iter <- tclVar(StudyS$Sd)
sd_<-tkentry(Saisi_, width=7, textvariable=n.iter, state="disabled")
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
intcpt_<-tkentry(Saisi_, width=7, textvariable=n.intcpt, state="disabled")
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ;
const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimCRM=function()
{
tkdestroy(Win_CRMB)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Param.c_ = function(...)
{
if (as.numeric(tclvalue((rbValue.M_)))==2)
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=7, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_",tkentry(Saisi_, width=7),envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
seed=1;target=NULL;Model=NULL
npat=NULL;nsim=1;x0=1
target=as.numeric(tclvalue(tkget((Target_))))
Model=as.numeric(tclvalue((rbValue.M_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
npat=as.numeric(tclvalue(tkget(n_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
seed=as.numeric(tclvalue(tkget((Seed_))))
sdv=as.numeric(tclvalue(tkget((sd_))))
if (Model == 1) {model=as.character("logistic");intcp=as.numeric(tclvalue(tkget(intcpt_)))}
if (Model == 2) {model=as.character("empiric");intcp=NULL}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("Names_Study", tclvalue(tkget(names.S_)), envir = as.environment(pos))
assign("StudyS",list(Name=paste(Names_Study),Nb_Dl=Nb_Dl,True=true,Prior=prior,Target=target,
Model=model,Npat=npat,Nsim=nsim,X0=x0, Intcpt=intcp, Sd=sdv,
Constrain=Const, Seed=seed), envir = as.environment(pos))
if (res.users == 1) {
cat("\n Submission in progress... Please wait... ")
e$ResSim <- dfcrm::crmsim(PI=StudyS$True, prior=StudyS$Prior,target=StudyS$Target,n=StudyS$Npat,
x0=StudyS$X0,nsim=StudyS$Nsim,method="bayes",model=StudyS$Model,count=FALSE,
intcpt=StudyS$Intcpt, scale=StudyS$Sd, restrict=StudyS$Constrain, seed=StudyS$Seed)
.RecapSim()
tk2notetab.select(net.CRMB_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
Target_<-tkentry(Saisi_, width=5)
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n_<-tkentry(Saisi_, width=5)
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_, command=.Param.c_) ; rb2.1_ <- tkradiobutton(Saisi_, command=.Param.c_)
rbValue.M_ <- tclVar(1)
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation",font=PoliceGenerale)
sd_<-tkentry(Saisi_, width=7)
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_",tkentry(Saisi_, width=7),envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=18)
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive CRM or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Continual Reassessment Method bayesian Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=dfcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRMB", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRMB, "630x472")
tkwm.geometry(Win_CRMB, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRMB, ilogo)
tktitle(Win_CRMB) <- "GUI CRMB"
tkpack.propagate(Win_CRMB, FALSE)
topMenu <- tk2menu(Win_CRMB)
tkconfigure(Win_CRMB, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command= function(){ tkdestroy(Win_CRMB);frameInit()})
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRMB))
}
frameInitCRM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRMB",tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRMB, "680x555")
tkwm.geometry(Win_CRMB, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRMB, ilogo)
tktitle(Win_CRMB) <- "GUI CRMB"
tkpack.propagate(Win_CRMB, FALSE)
topMenu <- tk2menu(Win_CRMB)
tkconfigure(Win_CRMB, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command= function(){ tkdestroy(Win_CRMB);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRMB))
assign("net.CRMB", tk2notebook(Win_CRMB, tabs = c("Prior calibration","Input parameters","Include","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRMB , fill = "both", expand = 1)
assign("Include", tk2notetab(net.CRMB , "Include"), envir = as.environment(pos))
tkpack.propagate(Include, FALSE)
assign("Resultas", tk2notetab(net.CRMB , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.CRMB , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("PriorCal", tk2notetab(net.CRMB , "Prior calibration"), envir = as.environment(pos))
tkpack.propagate(PriorCal, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save" ,tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_CRMB", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.Win_CRMB, row=9, column=2, rowspan=16)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL, envir = as.environment(pos))
assign("nuPrior", NULL, envir = as.environment(pos))
assign("etatPrior", FALSE, envir = as.environment(pos))
}
frameInitSIM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRMB",tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRMB, "660x595")
tkwm.geometry(Win_CRMB, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRMB, ilogo)
tktitle(Win_CRMB) <- "GUI CRMB"
tkpack.propagate(Win_CRMB, FALSE)
topMenu <- tk2menu(Win_CRMB)
tkconfigure(Win_CRMB, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command= function(){ tkdestroy(Win_CRMB);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRMB))
assign("net.CRMB_", tk2notebook(Win_CRMB, tabs = c("Input parameters","Results")), envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRMB_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.CRMB_ , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.CRMB_ , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkpack.propagate(m2_, FALSE)
}
frameInit()
}
.CRML=function(pos=1, e)
{
e$CRM.2=NULL
tclRequire("Tktable")
remplireRequid=function()
{
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
Model=as.numeric(tclvalue((rbValue.M)))
if (Model==1){Model.n="logistic"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (Model==2){Model.n="empiric"; intcpt=NULL}
Stop=as.numeric(tclvalue(rbValue.SC))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
assign("names_Study",'', envir = as.environment(pos))
assign("names_Study", tclvalue(tkget(names.S)), envir = as.environment(pos))
assign("Study", list(name=paste(names_Study),Nb_Dl=Nb_Dl,DL=DL,Target=Target,Model=Model,Model.n=Model.n,
Stop=Stop,N_Pat=N_Pat,N_pat_Level=N_pat_Level,halfwidthPrior=halfwidthPrior,
nuPrior=nuPrior, Intcpt=intcptPrior, Sd=sdPrior), envir = as.environment(pos))
differ=abs(Study$DL-Study$Target)
MTD=1
Pat_include=0
PT.data=NULL
assign("Res", list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data), envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(names_Study)
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','CRM',sep=':')
a2='Continual Reassessment Method (CRML) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'crml', sep='.'))
}
Study.file()
tk2notetab.select(net.CRML , "Include")
}
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
tk2notetab.select(net.CRML , "Input parameters")
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses <- nlevel
priorProbaf <- c()
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (tkget(eval(parse(text = paste('valp',i,sep='')))))
priorProbaf <- c(priorProbaf,as.numeric(tclvalue(n.iter)))
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),sticky="w",row=r,column=1)
}
if (any(priorProbaf <= 0) | any(priorProbaf >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(priorProbaf, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
SliderValue=tclVar(nlevel)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1,
state="disabled",orient="horiz")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(TargetPrior)
Target<-tkentry(Saisi, width=5,textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Models",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi) ; rb2.1 <- tkradiobutton(Saisi)
rbValue.M <- tclVar(modelPrior)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic", state="disabled", font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric", state="disabled",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(sdPrior)
sd.<-tkentry(Saisi,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=8,column=0, sticky="w")
tkgrid(sd., row=8,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(intcptPrior)
}else {tclVar("NA")}
intcpt.<-tkentry(Saisi, textvariable=n.iter, width=10, state="disabled")
tkgrid(Tintcpt., row=8,column=2, sticky="w")
tkgrid(intcpt., row=8,column=3, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam<- tclVar()
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
assign("etatPrior", TRUE, envir = as.environment(pos))
}
disabled.PriorCalib=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
if(is.tkwin(SaisiCal)){tkdestroy(SaisiCal)}
if(is.tkwin(Saisi.saveCal )){tkdestroy(Saisi.saveCal )}
assign("affCal.crmb", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCal.crmb, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar(Study$Nb_Dl)
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
for ( i in 1: Study$Nb_Dl)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(tkget(eval(parse(text = paste('val',i,sep='')))))
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCal.crmb,text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCal.crmb,state="disabled", width=8,textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
if(Study$Nb_Dl!=8)
{
for ( i in (Study$Nb_Dl+1):8)
{
r=10 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCal.crmb, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCal.crmb, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
Titre=tklabel(SaisiCal,text="Target DLT rate",font=PoliceGenerale)
n.iter=tclVar(round(TargetPrior,3))
Target.cal<-tkentry(SaisiCal,textvariable=n.iter,state="disabled", width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
n.iter=tclVar(halfwidthPrior)
halfwidth<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_halfwidth, row=3,column=0, sticky="w")
tkgrid(halfwidth, row=3,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal,state="disabled") ; rb2.1CAL <- tkradiobutton(SaisiCal,state="disabled")
assign("rbValue.MCAL", tclVar(modelPrior),envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
n.iter=tclVar(nuPrior)
nu<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_nu, row=6,column=0, sticky="w")
tkgrid(nu, row=6,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
n.iter=tclVar(Study$Sd)
sd.<-tkentry(SaisiCal,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=7,column=0, sticky="w")
tkgrid(sd., row=7,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(Study$Intcpt)}
else {tclVar("NA")}
assign("intcpt.",tkentry(SaisiCal, textvariable=n.iter, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,bg = "cornflower blue",state="disabled")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,bg="cornflower blue",state="disabled")
tkgrid(Validation, row=2)
}
PriorCalib=function(...)
{
.Crea.f.CAL=function(...)
{
assign("TargetPrior",as.numeric(tclvalue(tkget((Target.cal)))), envir = as.environment(pos))
assign("halfwidthPrior",as.numeric(tclvalue(tkget((halfwidth)))), envir = as.environment(pos))
assign("nuPrior",as.numeric(tclvalue(tkget(nu))), envir = as.environment(pos))
assign("nlevel",as.numeric(tclvalue(tkget((slider_Nb_DL.CAL)))), envir = as.environment(pos))
assign("modelPrior",as.numeric(tclvalue(((rbValue.MCAL)))), envir = as.environment(pos))
assign("sdPrior",as.numeric(tclvalue(tkget((sd.)))), envir = as.environment(pos))
assign("intcptPrior",as.numeric(tclvalue(tkget((intcpt.)))), envir = as.environment(pos))
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
if (TargetPrior>0.55) cat("\n Warning: Target DLT rate too high")
if (TargetPrior<0.15) cat("\n Warning: Target DLT rate too low")
if ((halfwidthPrior<=0)|(halfwidthPrior>0.5)) stop('Halfwidth of the indifference intervals incorrect!')
if ((halfwidthPrior<=0.5)&(halfwidthPrior>0.2)) cat("\n Warning: Try to reduce the value of the halfwidth of the indifference intervals ")
if ((nuPrior<1)|(nuPrior>Nb_Niv_DosesCAL)|(nuPrior%%1 != 0)) stop(paste('Prior guess of MTD incorrect, enter an integer between 1 and',Nb_Niv_DosesCAL))
if (modelPrior==1)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel=8, model="logistic", intcpt=intcptPrior)
}
if (modelPrior==2)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel=8, model="empiric")
}
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(round(e$prior[i],3))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,textvariable=n.iter),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_DosesCAL!=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
f.CALPrior=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8),envir = as.environment(pos)),row=r,column=1)
}
if(Nb_Niv_DosesCAL !=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Param.choice = function(...)
{
if (as.numeric(tclvalue((rbValue.MCAL)))==2)
{
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(SaisiCal, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale)
assign("intcpt.",tkentry(SaisiCal, width=10),envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
}
}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
SliderValue.CAL=tclVar('8')
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",command=f.CALPrior)
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
Target.cal<-tkentry(SaisiCal, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
halfwidth<-tkentry(SaisiCal, width=10)
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
rb2.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
assign("rbValue.MCAL", tclVar(1), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal s.deviation",font=PoliceGenerale)
sd.<-tkentry(SaisiCal, width=10)
tkgrid(Tsd., row=4,column=2, sticky="w")
tkgrid(sd., row=4,column=3, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=5,column=2, sticky="w")
tkgrid(intcpt., row=5,column=3, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
nu<-tkentry(SaisiCal, width=10)
tkgrid(lab_nu, row=7,column=0, sticky="w")
tkgrid(nu, row=7,column=1, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,command=.Crea.f.CAL,bg="cornflower blue")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,command=remplireRequid,bg="cornflower blue")
tkgrid(Validation, row=2)
}
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.crml or file.clsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
if (filef != "") {
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
}
if (extension == "crml") {
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$CRM.2 <- CRM.2
Open.CRM()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
}
}
if (extension == "lsim") {
load(file =paste(paste(names_Study,'clsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS, envir = as.environment(pos))
tkdestroy(Win_CRML)
frameInitSIM()
disabled.SimCRM()
}
}
pending_listing=function()
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
dataa=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(dataa)==0 )
{
msg <- paste("No patient pending",sep="")
tkmessageBox(message=msg)
}
if (nrow(dataa)>=1)
{
assign("tt.pend", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(tt.pend, "+650+400")
assign("tl", tklistbox(tt.pend,height=4,selectmode="single",background="white"), envir = as.environment(pos))
tkgrid(tklabel(tt.pend,text="Select a patient",font=PoliceGenerale))
tkgrid(tl)
numPatP=paste("Patient N'", as.character(dataa$patid),sep="")
for (i in (1:length(numPatP)))
{
tkinsert(tl,"end",numPatP[i])
}
tkselection.set(tl,0)
OK.but <- tkbutton(tt.pend,text=" OK ",command=.include.pending,bg="cornflower blue")
tkgrid(OK.but)
tkfocus(tt.pend)
}
}
.include.pending <- function()
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
data.pinding=Res$PT.data[which(Res$PT.data$pndg==1),]
data.inclus=Res$PT.data[which(Res$PT.data$pndg==0),]
numPatP=as.character(data.pinding$patid)
assign("Choice", as.numeric(numPatP[as.numeric(tkcurselection(tl))+1]), envir = as.environment(pos))
Inc=tktoplevel()
tkwm.geometry(Inc, "+650+400")
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre<-tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i))))
}
.Sauv2=function(...)
{
assign("DLT", as.numeric(tclvalue((rbValue.DLT))), envir = as.environment(pos))
Newpat=data.pinding[which(data.pinding$patid==Choice),]
Newpat$DLT=DLT
Newpat$pndg=0
DATA=rbind(data.inclus,Newpat)
if (nrow(DATA)!=0)
{
if (sum(DATA[,2])==0)
{
numpat=length(DATA[,2])+1
if (numpat!=1)
{
print('numpat')
print(numpat)
temp <- (numpat-1)/3
print('temp')
print(temp)
if (temp==trunc(temp))
{
print('temp==trunc(temp)')
print(trunc(temp))
Res$MTD <- DATA$DL[numpat-1]+1
if (Res$MTD>Study$Nb_Dl){Res$MTD <-DATA$DL[numpat-1]}
}
else
{Res$MTD <-DATA$DL[numpat-1]}
}
}
else
{
environment()
e$CRM.2 <- dfcrm::crm(prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1], conf.level = 0.95,
method = "mle", model = paste(Study$Model.n), intcpt=Study$Intcpt, scale=Study$Sd)
Res$MTD<-e$CRM.2$mtd
}
}
Res$PT.data[which(Res$PT.data$patid==Choice),]$pndg=0
Res$PT.data[which(Res$PT.data$patid==Choice),]$DLT=DLT
if (nrow(DATA)!=0) {
if (sum(DATA[,2])==0) {
save(Res,Study,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))}
else {CRM.2<- e$CRM.2; save(Res,Study,CRM.2,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))}
}
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRML", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRML,text="Validate",width=30,command=.Sauv2,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRML)
tkdestroy (tt.pend)
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-likelihood approach (CRML) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(Study$Model))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(Study$Stop))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRML,text="New patient",width=30,command=.include,bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRML,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRML, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_CRML)
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Continued reassessment method-likelihood approach (CRML) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(Study$Model))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(Study$Stop))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRML,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRML,text="Pending patient",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.CRML ,"Results")
tkgrid(Rec.Win_CRML, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
if (nrow(DATA)!=0)
{
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_CRML,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_CRML,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_CRML, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2]),
envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
if (!is.null(e$CRM.2)){
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for (i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,
total.tox=total.tox, ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="17",background="white")
tkgrid(t.d, row=2, column=0)
} else {print('Results are displayed once toxicity is observed')}
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],
Toxicity=Res$PT.data[,2])
if (!is.null(e$CRM.2)) {
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, n.patient=n.patient,total.tox=total.tox,
ptox=ptox, ptoxL=ptoxL, ptoxU=ptoxU), envir = as.environment(pos))
Da=data.frame(Study[1],Study[2],Study[4],Study[5],method="Continued reassessment method-likelihood approach (CRML) ",Res[2],Res[1])
DD=t(Da)
rownames(DD)=c("Name of study","Number of dose level","Target DLT rate","Model","Statistical method","Number of patients included", "Estimated MTD")
colnames(DD)=""
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
GrapheResults()
dev.off()
pdf(paste(paste(filef,"2",sep=""),"pdf",sep="."))
curvesIC()
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
setColWidths(wb, sheet2, cols=c(3,4), widths = 14.43)
setColWidths(wb, sheet2, cols=c(1,2,5,6,7), widths = 10.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:7,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}else {
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
writeDataTable(wb,sheet1,x=myRarray1)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
}
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphic",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=Export.Graph,bg="cornflower blue")
button3b=tkbutton(Resultas ,text="Dose-tox curves",width=20,command=Export.CurvesIC,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(button3b, row=5, column=3)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.include=function(...)
{
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
assign("Inc", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for ( i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
tkgrid(assign(paste('rDLT',2,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=2, text=paste("pending"))))
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))), envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))), envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1), envir = as.environment(pos))
assign("pndg", as.numeric (c(Res$PT.data[,4],as.numeric(tclvalue((rbValue.DLT)))==2)), envir = as.environment(pos))
Res$PT.data <- data.frame(DL=DL,DLT=DLT,patid=patid,pndg=pndg)
Res$Pat.included <- Res$Pat.included+1
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
if (nrow(DATA)!=0)
{
if (sum(DATA[,2])==0)
{
print('3+3')
numpat=length(DATA[,2])+1
if (numpat!=1)
{
temp <- (numpat-1)/3
if (temp==trunc(temp))
{
Res$MTD <- DATA$DL[numpat-1]+1
if (Res$MTD>Study$Nb_Dl){Res$MTD <-DATA$DL[numpat-1]}}
else
{Res$MTD <-DATA$DL[numpat-1]}
}
save(Res,Study,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
}
else
{
e$CRM.2 <- dfcrm::crm(prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1], conf.level = 0.95,
method = "mle", model =paste(Study$Model.n), intcpt=Study$Intcpt, scale=Study$Sd)
Res$MTD <- e$CRM.2$mtd
print('CRM')
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
}
}
load(file =paste(paste(names_Study,'crml',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
assign("Inc.Win_CRML", tkframe(Inc,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Inc.Win_CRML,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_CRML)
}
GrapheResults=function(...)
{
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
n=length(DATA[,1])
x=c(1:n)
y=DATA[,1]
z=DATA[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
Export.Graph=function()
{
GrapheResults()
}
curvesIC = function(...)
{
post.var <- e$CRM.2$post.var
crit <- qnorm(0.5 + e$CRM.2$conf.level/2)
doses=e$CRM.2$dosescaled
Fempi=function(doses,beta){doses^(exp(beta))}
Flogi=function(doses,beta){(1 + exp(-e$CRM.2$intcpt- exp(beta) * doses))^{-1}}
Fmodel <- switch(e$CRM.2$model,empiric=Fempi, logistic=Flogi)
plot(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),'l', lwd=2,xaxt="n",
ylim=c(0, 1),xlab="Dose level", ylab="Proba. of DLT")
axis(1, at = seq(1, length(e$CRM.2$prior), by = 1))
abline(h=e$CRM.2$target,col="blue",lty=2,lwd=2)
objtitle <-rbind("Dose-toxicity curve + 0.95_IC",paste(e$CRM.2$model, "model"))
title(main=objtitle)
legend('topright',c("Proba. of DLT", "IC(0.95)","target"),lty=c(1,1,2), col=c('black','red','blue'),lwd=2)
points(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),lwd=2)
if (post.var >= 0) {
lb <- e$CRM.2$estimate - crit * sqrt(post.var)
ub <- e$CRM.2$estimate + crit * sqrt(post.var)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,lb),col="red",lwd=2)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,ub),col="red",lwd=2)
}else{print('Confidence interval not calculated')}
}
Export.CurvesIC=function()
{
if (!is.null(e$CRM.2)) {
curvesIC()
}else {print('Results are displayed once toxicity is observed')}
}
NewCRM=function()
{
tkdestroy(Win_CRML)
frameInitCRM()
PriorCalib()
}
disabled.CRM=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.CRM=function()
{
tkdestroy(Win_CRML)
frameInitCRM()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save, row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal s.deviation",font=PoliceGenerale)
n.iter <- tclVar(Study$Sd)
sd.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tsd., row=6,column=2, sticky="w")
tkgrid(sd., row=6,column=3, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
n.iter <- tclVar(Study$Intcpt)
assign("intcpt.", tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
Titre=tklabel(Saisi,text="Names of study",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(Titre, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save Study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
WordExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
docx( ) %>%
addFlexTable(dframe %>%
FlexTable(header.cell.props = cellProperties( background.color = "#003366"),
header.text.props = textBold(color = "white"),
add.rownames = TRUE ) %>%
setZebraStyle(odd = "#DDDDDD", even = "#FFFFFF")) %>%
writeDoc(file = "ResExport.docx")
Save.word.infos <- tkmessageBox(title = "Word Export",
message = "File ResExport.docx saved in the current working directory of the R proces", icon = "info", type = "ok")
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','CRML',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'clsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'clsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
vect.X0=NULL
for (i in 1:StudyS$Npat)
{
vect.X0[i]=as.numeric(tclvalue(tkget(eval(parse(text = paste('valx',i,sep=''))))))
}
StudyS$X0 = vect.X0
if(is.unsorted(StudyS$X0)|(sum(is.na(StudyS$X0))==1)){stop(paste('Initial design must be a non-decreasing sequence of dose levels of length', StudyS$Npat))}
if(any(StudyS$X0<1)|any(StudyS$X0>StudyS$Nb_Dl)|any(StudyS$X0%%1 != 0)) stop(paste('Initial design incorrect, enter a sequence of dose levels between 1 and',StudyS$Nb_Dl))
assign("StudyS", StudyS, envir = as.environment(pos))
cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim <- dfcrm::crmsim(PI=StudyS$True, prior=StudyS$Prior,
target=StudyS$Target,n=StudyS$Npat,x0=StudyS$X0,nsim=StudyS$Nsim,method="mle",
model=StudyS$Model,count=FALSE, intcpt=StudyS$Intcpt, scale=StudyS$Sd, seed=StudyS$Seed)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Maximum likelihood (CRML) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=3)
tk2notetab.select(net.CRML_, "Results")
}
disabled.SimCRM=function()
{
.RecapSimB=function()
{
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Maximum likelihood (CRML) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
tkdestroy(Saisi.design_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
assign("Saisi.design_", tkframe(Design_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.design_, FALSE)
tkgrid(Saisi.design_, row=1, column=1, columnspan=8, rowspan=40)
Nb_Niv_Doses<- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
n_<-tkentry(Saisi_, width=5, textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0[1])
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,state="disabled") ; rb2.1_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Model == "logistic") {
rbValue.M_ <- tclVar(1)
n.intcpt <- tclVar(StudyS$Intcpt)}
if (StudyS$Model == "empiric") {
rbValue.M_ <- tclVar(2)
n.intcpt <- tclVar("NA")}
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation", font=PoliceGenerale)
n.iter <- tclVar(StudyS$Sd)
sd_<-tkentry(Saisi_, width=7, textvariable=n.iter, state="disabled")
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7, textvariable=n.intcpt, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ;
const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
Nb.x0<-StudyS$Npat
for ( i in 1: Nb.x0)
{
n.iter=tclVar(StudyS$X0[i])
if (i <= 15) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i,column=0)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter, state="disabled"),envir = as.environment(pos)),row=i,column=1)
}
if ((i > 15)&&(i <= 30)) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i-15,column=3)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter, state="disabled"),envir = as.environment(pos)),row=i-15,column=4)
}
if (i > 30) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i-30,column=6)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter, state="disabled"),envir = as.environment(pos)),row=i-30,column=7)
}
}
if (Nb.x0 <= 15) {
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
state="disabled",bg="cornflower blue")
tkgrid(ValInitD_, row=16, column=1)}
if ((Nb.x0 > 15)&&(Nb.x0 <= 30)) {
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
state="disabled",bg="cornflower blue")
tkgrid(ValInitD_, row=16, column=4)
}
if (Nb.x0 > 30) {
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
state="disabled",bg="cornflower blue")
tkgrid(ValInitD_, row=16,column=7)
}
.RecapSimB()
}
SimCRM=function()
{
tkdestroy(Win_CRML)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Param.c_= function(...)
{
if (as.numeric(tclvalue((rbValue.M_)))==2)
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=7, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
seed=1
target=as.numeric(tclvalue(tkget((Target_))))
Model=as.numeric(tclvalue((rbValue.M_)))
npat=as.numeric(tclvalue(tkget(n_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
sdv=as.numeric(tclvalue(tkget((sd_))))
seed=as.numeric(tclvalue(tkget((Seed_))))
assign("Names_Study", tclvalue(tkget(names.S_)), envir = as.environment(pos))
if (Model == 1) {model=as.character("logistic"); intcp=as.numeric(tclvalue(tkget((intcpt_))))}
if (Model == 2) {model=as.character("empiric"); intcp=NULL}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if (npat > 80) cat("\n TIP: Might need to maximize the window to validate initial design")
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
if (res.users == 1) {
tkdestroy(Saisi.design_)
assign("Saisi.design_", tkframe(Design_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.design_, FALSE)
tkgrid(Saisi.design_, row=1, column=1, columnspan=8, rowspan=40)
v.x0 <- dfcrm::getinit(prior=prior, target=target, nK=ifelse(npat < Nb_Dl*2, npat,round(npat/Nb_Dl)),n=npat, method = "mle", detail = FALSE)
for ( i in 1: npat)
{
ind <- floor(i/20.01)
n.iter=tclVar(round(v.x0[i],3))
if ((i > ind*20)&&(i <= (ind+1)*20)) {
tkgrid(assign(paste('labx',i,sep=''),tklabel(Saisi.design_, text=paste('Dose level P',i,sep=''),font=PoliceGenerale)),row=i-ind*20,column=3*ind)
tkgrid(assign(paste('valx',i,sep=''),tkentry(Saisi.design_, width=8,textvariable=n.iter),envir = as.environment(pos)),row=i-ind*20,column=3*ind+1)
}
}
ValInitD_=tkbutton(Saisi.design_ ,text="Validation Init Design",width=20,
command=.RecapSim,bg="cornflower blue")
tkgrid(ValInitD_, row=21, column=3*ind+1)
tk2notetab.select(net.CRML_, "Initial design")
assign("StudyS", list(Name=paste(Names_Study), Nb_Dl=Nb_Dl, True=true, Prior=prior, Target=target,
Model=model, Npat=npat,Nsim=nsim, X0=v.x0, Intcpt=intcp, Sd=sdv,
Constrain=Const, Seed=seed), envir = as.environment(pos))
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
assign("Target_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
assign("n_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,command=.Param.c_) ; rb2.1_ <- tkradiobutton(Saisi_,command=.Param.c_)
rbValue.M_ <- tclVar(1)
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal s.deviation",font=PoliceGenerale)
sd_<-tkentry(Saisi_, width=7)
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=9, column=0, sticky="w")
tkgrid(const1_, row=9, column=1, sticky="w")
tkgrid(const2_, row=10,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=11,column=0, sticky="w")
tkgrid(names.S_, row=11,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive CRM or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Continual Reassessment Method with Maximum
likelihood estimation Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=dfcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInitCRM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRML", tktoplevel(background = "black"), envir = as.environment(pos))
tkwm.geometry(Win_CRML, "680x555")
tkwm.geometry(Win_CRML, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRML, ilogo)
tktitle(Win_CRML) <- "GUI CRML"
tkpack.propagate(Win_CRML, FALSE)
topMenu <- tk2menu(Win_CRML)
tkconfigure(Win_CRML, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function (){tkdestroy(Win_CRML);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRML))
assign("net.CRML", tk2notebook(Win_CRML, tabs = c("Prior calibration","Input parameters","Include","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRML , fill = "both", expand = 1)
assign("Include", tk2notetab(net.CRML , "Include"), envir = as.environment(pos))
tkpack.propagate(Include, FALSE)
assign("Resultas", tk2notetab(net.CRML , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.CRML , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("PriorCal", tk2notetab(net.CRML , "Prior calibration"), envir = as.environment(pos))
tkpack.propagate(PriorCal, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_CRML", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.Win_CRML, row=9, column=2, rowspan=16)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL, envir = as.environment(pos))
assign("nuPrior", NULL, envir = as.environment(pos))
assign("etatPrior", FALSE, envir = as.environment(pos))
}
frameInitSIM=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRML", tktoplevel(background = "black"), envir = as.environment(pos))
tkwm.geometry(Win_CRML, "680x585")
tkwm.geometry(Win_CRML, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRML, ilogo)
tktitle(Win_CRML) <- "GUI CRML"
tkpack.propagate(Win_CRML, FALSE)
topMenu <- tk2menu(Win_CRML)
tkconfigure(Win_CRML, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function (){tkdestroy(Win_CRML);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRML))
assign("net.CRML_", tk2notebook(Win_CRML, tabs = c("Input parameters","Initial design","Results")), envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.CRML_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.CRML_ , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Design_", tk2notetab(net.CRML_ , "Initial design"), envir = as.environment(pos))
tkpack.propagate(Design_, FALSE)
assign("Required_", tk2notetab(net.CRML_ , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi.design_", tkframe(Design_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.design_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkpack.propagate(m2_, FALSE)
}
frameInit=function(){
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
assign("Win_CRML", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_CRML, "630x472")
tkwm.geometry(Win_CRML, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_CRML, ilogo)
tktitle(Win_CRML) <- "GUI CRML"
tkpack.propagate(Win_CRML, FALSE)
topMenu <- tk2menu(Win_CRML)
tkconfigure(Win_CRML, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study", command=function (){tkdestroy(Win_CRML);frameInit()})
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_CRML))
}
frameInit()
}
.TITECRM=function(pos=1, e)
{
e$ResSim = NULL
e$CRM.2 = NULL
tclRequire("Tktable")
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12), envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10), envir = as.environment(pos))
remplireRequid=function()
{
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
Model=as.numeric(tclvalue((rbValue.M)))
if (Model==1){Model.n="logistic"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (Model==2){Model.n="empiric"; intcpt=NULL}
Sdv=as.numeric(tclvalue(tkget(sd.)))
Stop=as.numeric(tclvalue(rbValue.SC))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
ObWin=as.numeric(tclvalue(tkget(ObWin)))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
if (ObWin <= 0 ) stop('Observation window incorrect')
assign("names_Study", tclvalue(tkget(names.S)), envir = as.environment(pos))
assign("Study", list(name=paste(names_Study),Nb_Dl=Nb_Dl,DL=DL,Target=Target,Model=Model,
Model.n=Model.n,Stop=Stop,N_Pat=N_Pat,N_pat_Level=N_pat_Level,Obs.wind=ObWin,
halfwidthPrior=halfwidthPrior,nuPrior=nuPrior, Sd=Sdv, Intcpt=intcpt), envir = as.environment(pos))
differ=abs(Study$DL-Study$Target)
MTD=1
for ( i in 1 : Study$Nb_Dl)
{
if (differ[i]==min(differ)) {MTD=i}
}
Pat_include=0
PT.data=NULL
assign("Res", list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data,ObWin=ObWin), envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(names_Study)
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','TiTE_CRM',sep=':')
a2='TiME TO EVENTS-Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'tcrm', sep='.'))
}
Study.file()
tk2notetab.select(net.TiTECRM , "Include")
}
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
tk2notetab.select(net.TiTECRM , "Input parameters")
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=2, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
priorProbaf <- c()
Nb_Niv_Doses <- nlevel
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (tkget(eval(parse(text = paste('valp',i,sep='')))))
priorProbaf <- c(priorProbaf,as.numeric(tclvalue(n.iter)))
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
if (any(priorProbaf <= 0) | any(priorProbaf >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(priorProbaf, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
SliderValue=tclVar(nlevel)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(TargetPrior)
Target<-tkentry(Saisi, width=5,textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi, state="disabled") ; rb2.1 <- tkradiobutton(Saisi, state="disabled")
rbValue.M <- tclVar(modelPrior)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal S. deviation",font=PoliceGenerale)
n.iter <- tclVar(sdPrior)
sd.<-tkentry(Saisi,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=8,column=0, sticky="w")
tkgrid(sd., row=8,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(intcptPrior)}
else {tclVar("NA")}
assign("intcpt.", tkentry(Saisi, textvariable=n.iter, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=8,column=2, sticky="w")
tkgrid(intcpt., row=8,column=3, sticky="w")
labagewin<-tklabel(Saisi, text="Observation window ",font=PoliceGenerale)
ObWin<-tkentry(Saisi, width=10)
tkgrid(labagewin, row=9,column=0, sticky="w")
tkgrid(ObWin, row=9,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam<- tclVar()
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=10,column=0, sticky="w")
tkgrid(names.S, row=10,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
assign("etatPrior", TRUE, envir = as.environment(pos))
}
disabled.PriorCalib=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
if(is.tkwin(SaisiCal)){tkdestroy(SaisiCal)}
if(is.tkwin(Saisi.saveCal )){tkdestroy(Saisi.saveCal )}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.saveCal, FALSE)
SliderValue.CAL=tclVar(Study$Nb_Dl)
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz", state="disabled")
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
for ( i in 1: Study$Nb_Dl)
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar (tkget(eval(parse(text = paste('val',i,sep='')))))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL,text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL,state="disabled", width=8,textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
if( Study$Nb_Dl!=8)
{
for ( i in (Study$Nb_Dl+1):8)
{
r=10 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
n.iter=tclVar(round(TargetPrior,3))
Target.cal<-tkentry(SaisiCal,textvariable=n.iter,state="disabled", width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
n.iter=tclVar(halfwidthPrior)
halfwidth<-tkentry(SaisiCal, width=10,textvariable=n.iter,state="disabled")
tkgrid(lab_halfwidth, row=3,column=0,columnspan=2, sticky="w")
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal,state="disabled") ; rb2.1CAL <- tkradiobutton(SaisiCal,state="disabled")
assign("rbValue.MCAL", tclVar(modelPrior), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
n.iter=tclVar(nuPrior)
nu<-tkentry(SaisiCal, width=10, textvariable=n.iter, state="disabled")
tkgrid(lab_nu, row=6,column=0, sticky="w")
tkgrid(nu, row=6,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="NormalS. deviation ",font=PoliceGenerale)
n.iter=tclVar(Study$Sd)
sd.<-tkentry(SaisiCal,textvariable=n.iter, width=10, state="disabled")
tkgrid(Tsd., row=7,column=0, sticky="w")
tkgrid(sd., row=7,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
n.iter <- if (modelPrior == 1) {tclVar(Study$Intcpt)}
else {tclVar("NA")}
assign("intcpt.", tkentry(SaisiCal, textvariable=n.iter, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,bg = "cornflower blue",state="disabled")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,bg="cornflower blue",state="disabled")
tkgrid(Validation, row=2)
}
PriorCalib=function(...)
{
.Crea.f.CAL=function(...)
{
assign("TargetPrior", as.numeric(tclvalue(tkget((Target.cal)))), envir = as.environment(pos))
assign("halfwidthPrior", as.numeric(tclvalue(tkget((halfwidth)))), envir = as.environment(pos))
assign("nuPrior", as.numeric(tclvalue(tkget(nu))), envir = as.environment(pos))
assign("nlevel", as.numeric(tclvalue(tkget((slider_Nb_DL.CAL)))), envir = as.environment(pos))
assign("modelPrior", as.numeric(tclvalue(((rbValue.MCAL)))), envir = as.environment(pos))
assign("sdPrior", as.numeric(tclvalue(tkget((sd.)))), envir = as.environment(pos))
assign("intcptPrior", as.numeric(tclvalue(tkget((intcpt.)))), envir = as.environment(pos))
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
if (TargetPrior>0.55) cat("\n Warning: Target DLT rate too high")
if (TargetPrior<0.15) cat("\n Warning: Target DLT rate too low")
if ((halfwidthPrior<=0)|(halfwidthPrior>0.5)) stop('Halfwidth of the indifference intervals incorrect!')
if ((halfwidthPrior<=0.5)&(halfwidthPrior>0.2)) cat("\n Warning: Try to reduce the value of the halfwidth of the indifference intervals ")
if ((nuPrior<1)|(nuPrior>Nb_Niv_DosesCAL)|(nuPrior%%1 != 0)) stop(paste('Prior guess of MTD incorrect, enter an integer between 1 and',Nb_Niv_DosesCAL))
if (modelPrior==1)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior, nlevel,
model="logistic", intcpt=intcptPrior)
}
if (modelPrior==2)
{
e$prior <- dfcrm::getprior(halfwidthPrior, TargetPrior, nuPrior,
nlevel, model="empiric")
}
for ( i in c(1:Nb_Niv_DosesCAL))
{
r=10 + i
assign(paste('prior',i,sep='_'),round(e$prior[i],3),envir = as.environment(pos))
n.iter=tclVar(round(e$prior[i],3))
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,textvariable=n.iter),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_DosesCAL!=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
f.CALPrior=function(...)
{
if(is.tkwin(affCAL)){tkdestroy(affCAL)}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("Nb_Niv_DosesCAL", as.numeric(tclvalue((SliderValue.CAL))), envir = as.environment(pos))
for ( i in 1: Nb_Niv_DosesCAL)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8),envir = as.environment(pos)),row=r,column=1)
}
if(Nb_Niv_DosesCAL !=8)
{
for ( i in (Nb_Niv_DosesCAL+1):8)
{
r=10 + i
tkgrid(assign(paste('labp',i,sep=''),tklabel(affCAL, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valp',i,sep=''),tkentry(affCAL, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Param.choice = function(...)
{
if (as.numeric(tclvalue((rbValue.MCAL)))==2)
{
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(SaisiCal, width=10, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(SaisiCal, text="intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
}
assign("affCAL", tkframe(PriorCal,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(affCAL, row=10)
assign("SaisiCal", tkframe(PriorCal,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(SaisiCal, FALSE)
tkgrid(SaisiCal, row=3)
assign("Saisi.saveCal", tkframe(PriorCal,borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.saveCal, FALSE)
SliderValue.CAL=tclVar('8')
slider_Nb_DL.CAL <- tkscale(SaisiCal, from=2, to=8,showvalue=T, variable=SliderValue.CAL, resolution=1, orient="horiz",command=f.CALPrior)
tkgrid(tklabel(SaisiCal,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL.CAL , row=1,column=1, sticky="w")
Titre=tklabel(SaisiCal,text="Target DLT rate ",font=PoliceGenerale)
Target.cal<-tkentry(SaisiCal, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target.cal, row=2, column=1, sticky="w")
lab_halfwidth<-tklabel(SaisiCal, text="The desired halfwidth of the indifference intervals",font=PoliceGenerale)
halfwidth<-tkentry(SaisiCal, width=10)
tkgrid(lab_halfwidth, row=3,column=0, sticky="w", columnspan=2)
tkgrid(halfwidth, row=3,column=2, sticky="w")
Titre=tklabel(SaisiCal,text="Model",font=PoliceGenerale)
rb1.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice) ;
rb2.1CAL <- tkradiobutton(SaisiCal, command=.Param.choice)
assign("rbValue.MCAL", tclVar(1), envir = as.environment(pos))
tkconfigure(rb1.1CAL,variable=rbValue.MCAL,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1CAL,variable=rbValue.MCAL,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=4,column=0, sticky="w")
tkgrid(rb1.1CAL, row=4,column=1, sticky="w")
tkgrid(rb2.1CAL, row=5,column=1, sticky="w")
Tsd.<-tklabel(SaisiCal, text="Normal S. deviation ",font=PoliceGenerale)
sd.<-tkentry(SaisiCal, width=10)
tkgrid(Tsd., row=6,column=0, sticky="w")
tkgrid(sd., row=6,column=1, sticky="w")
Tintcpt.<-tklabel(SaisiCal, text="Intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(SaisiCal, width=10), envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
lab_nu<-tklabel(SaisiCal, text="The prior guess of MTD",font=PoliceGenerale)
nu<-tkentry(SaisiCal, width=10)
tkgrid(lab_nu, row=7,column=0, sticky="w")
tkgrid(nu, row=7,column=1, sticky="w")
p<-tklabel(SaisiCal, text=" ",font=PoliceGenerale)
tkgrid(p, row=8)
getprio=tkbutton(SaisiCal ,text="Run",width=20,command=.Crea.f.CAL,bg = "cornflower blue")
tkgrid(getprio , row=9, column=3)
tkgrid(Saisi.saveCal,column=0,rowspan=2 ,sticky="e")
Validation=tkbutton(Saisi.saveCal ,text="Validation of prior",width=20,command=remplireRequid,bg="cornflower blue")
tkgrid(Validation, row=2)
}
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.tcrm or file.tcsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
if (extension == "tcrm") {
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$CRM.2 <- CRM.2
Open.CRM()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(Include)
}
}
}
}
if (extension == "csim") {
load(file =paste(paste(names_Study,'tcsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS, envir = as.environment(pos))
tkdestroy(Win_TiTECRM)
frameInitSIM()
disabled.SimCRM()
}
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("TiTE-Continued reassessment method-bayesian approach (TiTECRM) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_TiTECRM,text="New patient",width=30,command=.Include,bg="cornflower blue")
Modif=tkbutton(Rec.Win_TiTECRM,text="Modif patient data",width=30,command=.modif.data.patient,bg="cornflower blue")
tkgrid(Rec.Win_TiTECRM, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
}
.modif.data.patient= function (...)
{
.modif.data=function (...)
{
assign("id.modif", as.numeric(tkcurselection(tlm)) + 1, envir = as.environment(pos))
tkdestroy(tt.modif)
m.data=Res$PT.data[id.modif,]
win.m <- tktoplevel()
dlt. <- tclVar(m.data[,2])
level. <- tclVar(m.data[,1])
followup. <- tclVar(m.data[,4])
lab.id. <- tklabel(win.m,text=paste("Patient N_",id.modif),font=PoliceGenerale)
tkgrid(lab.id., row=0, columnspan=2)
lab.level. <- tklabel(win.m,text=paste("Dose level"),font=PoliceGenerale)
tkgrid(lab.level., row=1, columnspan=2)
assign("win.level", tk2entry(win.m, width = "3", textvariable = level.), envir = as.environment(pos))
tkgrid(win.level,row=1,column=2)
lab.dlt. <- tklabel(win.m,text=paste("DLT (1= 'Yes', 0='No')"),font=PoliceGenerale)
tkgrid(lab.dlt., row=3, columnspan=2)
assign("win.dlt", tk2entry(win.m, width = "3", textvariable = dlt.), envir = as.environment(pos))
tkgrid(win.dlt,row=3,column=2)
lab.fup. <- tklabel(win.m,text=paste("follow-up","<=",Res$ObWin),font=PoliceGenerale)
tkgrid(lab.fup., row=5, columnspan=2)
assign("win.fup", tk2entry(win.m, width = "3", textvariable = followup.), envir = as.environment(pos))
tkgrid(win.fup,row=5,column=2)
onOK <- function() {
new.dlt. <- as.numeric(tclvalue(tkget(win.dlt)))
new.level <- as.numeric(tclvalue(tkget(win.level)))
new.fup <- as.numeric(tclvalue(tkget(win.fup)))
Res$PT.data[id.modif,c(2,1,4)] <- c(new.dlt.,new.level,new.fup)
e$CRM.2 <- dfcrm::titecrm(prior=Study$DL, target=Study$Target, tox=Res$PT.data[,2],level=Res$PT.data[,1], conf.level = 0.95,
model = paste(Study$Model.n), followup=Res$PT.data[,4], obswin=Res$ObWin, intcpt=Study$Intcpt,
scale=Study$Sd)
Res$MTD <- e$CRM.2$mtd
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
tkdestroy(win.m)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
}
win.OK <-tkbutton(win.m, text = "OK", width = 10, command = onOK, bg="cornflower blue")
tkgrid(win.OK)
}
m.data=Res$PT.data
if (is.null(m.data))
{
msg <- paste("No patient included",sep="")
tkmessageBox(message=msg)
}
if (!is.null(m.data))
{
if (nrow(m.data)>=1)
{
tt.modif=tktoplevel()
tkwm.geometry(tt.modif, "+650+400")
assign("tlm", tklistbox(tt.modif,height=nrow(m.data)+1,selectmode="single",background="white"),
envir = as.environment(pos))
tkgrid(tklabel(tt.modif,text="Select a patient",font=PoliceGenerale))
tkgrid(tlm)
patlist=paste(" Patient N_", as.character(m.data$patid),sep="")
for (i in (1:length(patlist)))
{
tkinsert(tlm,"end",patlist[i])
}
tkselection.set(tlm,0)
OK.but <-tkbutton(tt.modif,text=" OK ",command=.modif.data,bg="cornflower blue")
tkgrid(OK.but)
}
}
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_TiTECRM)
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("TiTE-Continued reassessment method-bayesian approach (TiTECRM) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model==1,"Logistic","Empiric")))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
print('CAS 1')
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_TiTECRM,text="New patient",width=30, state="disabled",bg="cornflower blue")
Modif=tkbutton(Rec.Win_TiTECRM,text="Modif patient data",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.TiTECRM , "Resultas")
print(' Fin CAS 1')
tkgrid(Rec.Win_TiTECRM, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
}
if (nrow(DATA)!=0)
{
print('CAS 2')
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
Save=tkbutton(Rec.Win_TiTECRM,text="New patient",width=30, state="disabled",bg="cornflower blue")
Modif=tkbutton(Rec.Win_TiTECRM,text="Modif patient data",width=30,state="disabled",bg="cornflower blue")
tkgrid(Rec.Win_TiTECRM, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
print(' Fin CAS 2')
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2],
followup=Res$PT.data[,4], stringsAsFactors=FALSE), envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, Nb_patient=n.patient,
Nb_tox=total.tox, P_tox=ptox, P_toxL=ptoxL, P_toxU=ptoxU), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="15",background="white")
tkgrid(t.d, row=2, column=0)
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=Res$PT.data[,3],dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2],
followup=Res$PT.data[,4])
Prior=round(e$CRM.2$prior,3)
n.patient=NULL
total.tox=NULL
ptox=round(e$CRM.2$ptox,3)
ptoxL=round(e$CRM.2$ptoxL,3)
ptoxU=round(e$CRM.2$ptoxU,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=Prior, Nb_patient=n.patient,
Nb_tox=total.tox, P_tox=ptox, P_toxL=ptoxL, P_toxU=ptoxU), envir = as.environment(pos))
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
GrapheResults()
dev.off()
pdf(paste(paste(filef,"2",sep=""),"pdf",sep="."))
curvesIC()
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=c(1,3,4), widths = 12.43)
setColWidths(wb, sheet1, cols=2, widths = 14.43)
setColWidths(wb, sheet2, cols=3, widths = 14.43)
setColWidths(wb, sheet2, cols=c(1,2,4,5,6,7), widths = 10.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:4,rows=1)
addStyle(wb,sheet2,style,cols=1:7,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphic",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=Export.Graph,bg="cornflower blue")
button3b=tkbutton(Resultas ,text="Dose-tox curves",width=20,command=Export.CurvesIC,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(button3b, row=5, column=3)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.Include=function(...)
{
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
assign("inc", tktoplevel(), envir = as.environment(pos))
tkwm.geometry(inc, "+550+270")
assign("mm", tkframe(inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(mm)
assign("Titre", tklabel(mm,text="Treated dose level",font=PoliceGenerale), envir = as.environment(pos))
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for ( i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("inc.mm1", tkframe(inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(inc.mm1)
Titre <- tklabel(inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Fup", tkframe(inc,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Fup)
TitreFup <- tklabel(Fup,text="Follow-up Time")
tkgrid(TitreFup, row=0, columnspan=2)
val=tclVar(Res$ObWin)
assign("Followup", tkentry(Fup,textvariable=val, width=10), envir = as.environment(pos))
tkgrid(Followup)
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))), envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))), envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1), envir = as.environment(pos))
followup2=c(Res$PT.data[,4], as.numeric(tclvalue(tkget((Followup)))))
Res$PT.data<-data.frame(DL=DL,DLT=DLT,patid=patid,followup=followup2)
Res$Pat.included<-Res$Pat.included+1
print(Res$PT.data)
DATA=Res$PT.data
if (nrow(DATA)!=0)
{
e$CRM.2 <- dfcrm::titecrm(prior=Study$DL, target=Study$Target, tox=DATA[,2],level=DATA[,1], conf.level = 0.95,
model = paste(Study$Model.n), followup=DATA$followup, obswin=Res$ObWin, intcpt=Study$Intcpt,
scale=Study$Sd)
Res$MTD<-e$CRM.2$mtd
}
if (nrow(DATA)!=0){
CRM.2 <- e$CRM.2
save(Res,Study,CRM.2,file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))}
load(file =paste(paste(names_Study,'tcrm',sep='-'),'RData',sep='.'))
tkdestroy(inc)
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if(Res$Pat.included==1)
{
disabled.CRM()
if (etatPrior==TRUE)
{disabled.PriorCalib()}
if (etatPrior==FALSE)
{tkdestroy(PriorCal)}
}
}
inc.Win_TiTECRM<- tkframe(inc,relief="groove",borderwidth=3)
Save=tkbutton(inc.Win_TiTECRM,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(inc.Win_TiTECRM)
}
GrapheResults=function(...)
{
DATA=Res$PT.data
n=length(DATA[,1])
x=c(1:n)
y=DATA[,1]
z=DATA[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
curvesIC = function(...)
{
post.var <- e$CRM.2$post.var
crit <- qnorm(0.5 + e$CRM.2$conf.level/2)
doses=e$CRM.2$dosescaled
Fempi=function(doses,beta){doses^(exp(beta))}
Flogi=function(doses,beta){(1 + exp(-e$CRM.2$intcpt- exp(beta) * doses))^{-1}}
Fmodel <- switch(e$CRM.2$model,empiric=Fempi, logistic=Flogi)
plot(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),'l', lwd=2,xaxt="n",
ylim=c(0, 1),xlab="Dose level", ylab="Proba. of DLT")
axis(1, at = seq(1, length(e$CRM.2$prior), by = 1))
abline(h=e$CRM.2$target,col="blue",lty=2,lwd=2)
objtitle <-rbind("Dose-toxicity curve + 0.95_IC",paste(e$CRM.2$model, "model"))
title(main=objtitle)
legend('topright',c("Proba. of DLT", "IC(0.95)","target"),lty=c(1,1,2), col=c('black','red','blue'),lwd=2)
points(c(1:length(e$CRM.2$prior)),Fmodel(doses,e$CRM.2$estimate),lwd=2)
if (post.var >= 0) {
lb <- e$CRM.2$estimate - crit * sqrt(post.var)
ub <- e$CRM.2$estimate + crit * sqrt(post.var)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,lb),col="red",lwd=2)
lines(c(1:length(e$CRM.2$prior)),Fmodel(doses,ub),col="red",lwd=2)
}else{print('Confidence interval not calculated')}
}
Export.CurvesIC=function()
{
curvesIC()
}
Export.Graph=function()
{
GrapheResults()
}
NewCRM=function()
{
tkdestroy(Win_TiTECRM)
frameInitCRM()
PriorCalib()
}
disabled.CRM=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=2, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses<- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Nam_ObWin<- tclVar(Res$ObWin)
labagewin<-tklabel(Saisi, text="Observation window ",font=PoliceGenerale)
ObWin<-tkentry(Saisi, width=10,textvariable=Nam_ObWin,state="disabled")
tkgrid(labagewin, row=8,column=0, sticky="w")
tkgrid(ObWin, row=8,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.CRM=function()
{
tkdestroy(Win_TiTECRM)
frameInitCRM()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=2, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5, textvariable=n.iter,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w")
tkgrid(NBpat, row=5,column=1, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
rb1.1 <- tkradiobutton(Saisi,state="disabled") ; rb2.1 <- tkradiobutton(Saisi,state="disabled")
rbValue.M <- tclVar(Study$Model)
tkconfigure(rb1.1,variable=rbValue.M,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1,variable=rbValue.M,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre, row=6,column=0, sticky="w")
tkgrid(rb1.1, row=6,column=1, sticky="w")
tkgrid(rb2.1, row=7,column=1, sticky="w")
Tsd.<-tklabel(Saisi, text="Normal S. deviation ",font=PoliceGenerale)
n.iter <- tclVar(Study$Sd)
sd.<-tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tsd., row=6,column=2, sticky="w")
tkgrid(sd., row=6,column=3, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
n.iter <- tclVar(Study$Intcpt)
assign("intcpt.", tkentry(Saisi, width=10, textvariable=n.iter ,state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt., row=7,column=2, sticky="w")
tkgrid(intcpt., row=7,column=3, sticky="w")
Nam_ObWin<- tclVar(Res$ObWin)
labagewin<-tklabel(Saisi, text="Observation window ",font=PoliceGenerale)
ObWin<-tkentry(Saisi, width=10,textvariable=Nam_ObWin,state="disabled")
tkgrid(labagewin, row=8,column=0, sticky="w")
tkgrid(ObWin, row=8,column=1, sticky="w")
Titre=tklabel(Saisi,text="Names of study",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(Titre, row=9,column=0, sticky="w")
tkgrid(names.S, row=9,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
WordExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
docx( ) %>%
addFlexTable(dframe %>%
FlexTable(header.cell.props = cellProperties( background.color = "#003366"),
header.text.props = textBold(color = "white"),
add.rownames = TRUE ) %>%
setZebraStyle(odd = "#DDDDDD", even = "#FFFFFF")) %>%
writeDoc(file = "ResExport.docx")
Save.word.infos <- tkmessageBox(title = "Word Export",
message = "File ResExport.docx saved in the current working directory of the R proces", icon = "info", type = "ok")
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','TITE-CRMB',sep=':')
a2='Time-To-Event Continual Reassessment Method (TITE-CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'tcsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'tcsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-o-Event Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Bayesian approach (TITE-CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Patient arrival rate (per obs. window)"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Rate))
aff_13.0<-tklabel(Rec.fr,text=paste("Patient accrual scheme"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Accrual))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
disabled.SimCRM=function()
{
.RecapSimB=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','TITE-CRMB',sep=':')
a2='Continual Reassessment Method (CRM) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'tcsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'tcsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "Files saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=16)
PriorRes=paste(round(e$ResSim$prior[1],3))
TrueRes=paste(round(e$ResSim$PI[1],3))
MTDRes=paste(round(e$ResSim$MTD[1],3))
ToxRes=paste(round(e$ResSim$tox[1],3))
LevelRes=paste(round(e$ResSim$level[1],3))
for( i in 2 : length(e$ResSim$prior))
{
PriorRes=paste(PriorRes,paste(round(e$ResSim$prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(e$ResSim$PI[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$MTD[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$tox[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-to-Event Continued reassessment method "))
aff_1.2<-tklabel(Rec.fr,text=paste("Bayesian approach (TITE-CRMB) "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(StudyS$Model))
aff_8.0<-tklabel(Rec.fr,text=paste("Distribution of the MTD estimates"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$n))
aff_9.0<-tklabel(Rec.fr,text=paste("Average number of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Patient arrival rate (per obs. window)"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Rate))
aff_13.0<-tklabel(Rec.fr,text=paste("Patient accrual scheme"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Accrual))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkgrid(aff_1.2, row=5, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkconfigure(aff_1.2, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.save_, row=17, column=0)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,e$ResSim$MTD,e$ResSim$level,e$ResSim$tox))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.",
"Av. patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=round(ResExp_,3)),bg="cornflower blue")
tkgrid(WordExp_, row=1)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=2)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=3)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
Nb_Niv_Doses <- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
assign("n_", tkentry(Saisi_, width=5, textvariable=n.iter ,state="disabled"), envir = as.environment(pos))
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model", font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,state="disabled") ; rb2.1_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Model == "logistic") {
rbValue.M_ <- tclVar(1)
n.intcpt <- tclVar(StudyS$Intcpt)}
if (StudyS$Model == "empiric") {
rbValue.M_ <- tclVar(2)
n.intcpt <- tclVar("NA")}
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal S. deviation ", font=PoliceGenerale)
n.iter <- tclVar(StudyS$Sd)
sd_<-tkentry(Saisi_, width=7, textvariable=n.iter, state="disabled")
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7, textvariable=n.intcpt, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Tobsw_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Obswin)
Obsw_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Tobsw_, row=9,column=0, sticky="w")
tkgrid(Obsw_, row=9,column=1, sticky="w")
Trate_<-tklabel(Saisi_, text="Expected number of arrivals per
observation window",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Rate)
Rate_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Trate_, row=10,column=0, sticky="w")
tkgrid(Rate_, row=10,column=1, sticky="w")
Taccrual_=tklabel(Saisi_,text="Patient accrual scheme",font=PoliceGenerale)
rbacc.1_ <- tkradiobutton(Saisi_,state="disabled") ; rbacc.2_ <- tkradiobutton(Saisi_,state="disabled")
if (StudyS$Accrual == "fixed") {rbAcc.M_ <- tclVar(1)}
if (StudyS$Accrual == "poisson") {rbAcc.M_ <- tclVar(2)}
tkconfigure(rbacc.1_,variable=rbAcc.M_,value=1, text="fixed",font=PoliceGenerale)
tkconfigure(rbacc.2_,variable=rbAcc.M_,value=2, text="poisson",font=PoliceGenerale)
tkgrid(Taccrual_, row=11,column=0, sticky="w")
tkgrid(rbacc.1_, row=11,column=1, sticky="w")
tkgrid(rbacc.2_, row=12,column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_,state="disabled") ;
const2_ <- tkradiobutton(Saisi_,state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=11, column=2, sticky="w")
tkgrid(const1_, row=11, column=3, sticky="w")
tkgrid(const2_, row=12,column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size",font=PoliceGenerale)
tkgrid(Tstop_, row=13,column=0,columnspan=4, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=14,column=0, sticky="w")
tkgrid(names.S_,row=14,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimCRM=function()
{
tkdestroy(Win_TiTECRM)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Param.c_= function(...)
{
if (as.numeric(tclvalue((rbValue.M_)))==2)
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=7, state="disabled"), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
target=as.numeric(tclvalue(tkget((Target_))))
Model=as.numeric(tclvalue((rbValue.M_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
npat=as.numeric(tclvalue(tkget(n_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
obswin=as.numeric(tclvalue(tkget((Obsw_))))
rate=as.numeric(tclvalue(tkget((Rate_))))
Accrual=as.numeric(tclvalue((rbAcc.M_)))
seed=as.numeric(tclvalue(tkget((Seed_))))
sdv=as.numeric(tclvalue(tkget((sd_))))
assign("Names_Study", tclvalue(tkget(names.S_)), envir = as.environment(pos))
if (Model == 1) {model=as.character("logistic"); intcp=as.numeric(tclvalue(tkget((intcpt_))))}
if (Model == 2) {model=as.character("empiric");intcp=NULL}
if (Accrual == 1) {accrual=as.character("fixed")}
if (Accrual == 2) {accrual=as.character("poisson")}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if (obswin <= 0 ) stop('Observation window incorrect')
if (rate <= 0 ) stop('Expected number of arrivals per observation window must be strictly positive')
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("StudyS", list(Name=paste(Names_Study),Nb_Dl=Nb_Dl,True=true,Prior=prior,Target=target,
Model=model,Npat=npat,Nsim=nsim,X0=x0,Obswin=obswin,
Rate=rate,Accrual=accrual, Intcpt=intcp, Sd=sdv, Constrain=Const, Seed=seed),
envir = as.environment(pos))
if (res.users == 1) {
cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim <- dfcrm::titesim(PI=StudyS$True, prior=StudyS$Prior,target=StudyS$Target,n=StudyS$Npat,
x0=StudyS$X0,nsim=StudyS$Nsim, obswin=StudyS$Obswin, rate=StudyS$Rate,
accrual=StudyS$Accrual, method="bayes",model=StudyS$Model,count=FALSE,
intcpt=StudyS$Intcpt, scale=StudyS$Sd, restrict=StudyS$Constrain, seed=StudyS$Seed)
.RecapSim()
tk2notetab.select(net.TiTECRM_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
assign("Target_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Titre_=tklabel(Saisi_,text="Sample size",font=PoliceGenerale)
assign("n_", tkentry(Saisi_, width=5), envir = as.environment(pos))
tkgrid(Titre_, row=3, column=0, sticky="w")
tkgrid(n_, row=3, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=6,column=0, sticky="w")
tkgrid(Seed_, row=6,column=1, sticky="w")
Titre_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
rb1.1_ <- tkradiobutton(Saisi_,command=.Param.c_) ; rb2.1_ <- tkradiobutton(Saisi_,command=.Param.c_)
rbValue.M_ <- tclVar(1)
tkconfigure(rb1.1_,variable=rbValue.M_,value=1, text="Logistic",font=PoliceGenerale)
tkconfigure(rb2.1_,variable=rbValue.M_,value=2, text="Empiric",font=PoliceGenerale)
tkgrid(Titre_, row=7,column=0, sticky="w")
tkgrid(rb1.1_, row=7,column=1, sticky="w")
tkgrid(rb2.1_, row=8,column=1, sticky="w")
Tsd_<-tklabel(Saisi_, text="Normal S. deviation",font=PoliceGenerale)
sd_<-tkentry(Saisi_, width=7)
tkgrid(Tsd_, row=7,column=2, sticky="w")
tkgrid(sd_, row=7,column=3, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=7), envir = as.environment(pos))
tkgrid(Tintcpt_, row=8,column=2, sticky="w")
tkgrid(intcpt_, row=8,column=3, sticky="w")
Tobsw_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
Obsw_<-tkentry(Saisi_, width=10)
tkgrid(Tobsw_, row=9,column=0, sticky="w")
tkgrid(Obsw_, row=9,column=1, sticky="w")
Trate_<-tklabel(Saisi_, text="Expected number of arrivals per
observation window",font=PoliceGenerale)
Rate_<-tkentry(Saisi_, width=10)
tkgrid(Trate_, row=10,column=0, sticky="w")
tkgrid(Rate_, row=10,column=1, sticky="w")
Taccrual_=tklabel(Saisi_,text="Patient accrual scheme",font=PoliceGenerale)
rbacc.1_ <- tkradiobutton(Saisi_) ; rbacc.2_ <- tkradiobutton(Saisi_)
rbAcc.M_ <- tclVar(1)
tkconfigure(rbacc.1_,variable=rbAcc.M_,value=1, text="fixed",font=PoliceGenerale)
tkconfigure(rbacc.2_,variable=rbAcc.M_,value=2, text="poisson",font=PoliceGenerale)
tkgrid(Taccrual_, row=11,column=0, sticky="w")
tkgrid(rbacc.1_, row=11,column=1, sticky="w")
tkgrid(rbacc.2_, row=12,column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=11, column=2, sticky="w")
tkgrid(const1_, row=11, column=3, sticky="w")
tkgrid(const2_, row=12,column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size",font=PoliceGenerale)
tkgrid(Tstop_, row=13,column=0,columnspan=4, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=14,column=0, sticky="w")
tkgrid(names.S_,row=14,column=1, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive TITECRM or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Time-to-Event Continual Reassessment Method Bayesian Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=dfcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit=function(){
assign("Win_TiTECRM", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_TiTECRM, "630x500")
tkwm.geometry(Win_TiTECRM, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TiTECRM, ilogo)
tktitle(Win_TiTECRM) <- "GUI TiTE-CRM"
tkpack.propagate(Win_TiTECRM, FALSE)
topMenu <- tk2menu(Win_TiTECRM)
tkconfigure(Win_TiTECRM, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive TiTE-CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="TiTE-CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){tkdestroy(Win_TiTECRM);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TiTECRM))
}
frameInitCRM=function(){
assign("Win_TiTECRM", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_TiTECRM, "680x575")
tkwm.geometry(Win_TiTECRM, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TiTECRM, ilogo)
tktitle(Win_TiTECRM) <- "GUi TiTECRM"
tkpack.propagate(Win_TiTECRM, FALSE)
names_Study=''
topMenu <- tk2menu(Win_TiTECRM)
tkconfigure(Win_TiTECRM, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="Tite-CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){tkdestroy(Win_TiTECRM);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TiTECRM))
assign("net.TiTECRM", tk2notebook(Win_TiTECRM, tabs = c("Prior calibration","Input parameters",
"Include","Results")), envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TiTECRM , fill = "both", expand = 1)
assign("Include", tk2notetab(net.TiTECRM, "Include"), envir = as.environment(pos))
tkpack.propagate(Include, FALSE)
assign("Resultas", tk2notetab(net.TiTECRM, "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.TiTECRM, "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("PriorCal", tk2notetab(net.TiTECRM, "Prior calibration"), envir = as.environment(pos))
tkpack.propagate(PriorCal, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2), envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_TiTECRM", tkframe(Include,relief="groove",borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.Win_TiTECRM, row=9, column=2, rowspan=16)
assign("Rec.mm0",tkframe(Include, borderwidth=3), envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL, envir = as.environment(pos))
assign("nuPrior", NULL, envir = as.environment(pos))
assign("etatPrior", FALSE, envir = as.environment(pos))
}
frameInitSIM=function(){
assign("Win_TiTECRM", tktoplevel(background = "light steel blue"), envir = as.environment(pos))
tkwm.geometry(Win_TiTECRM, "690x690")
tkwm.geometry(Win_TiTECRM, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TiTECRM, ilogo)
tktitle(Win_TiTECRM) <- "GUi TiTECRM"
tkpack.propagate(Win_TiTECRM, FALSE)
names_Study=''
topMenu <- tk2menu(Win_TiTECRM)
tkconfigure(Win_TiTECRM, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
QuiterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Exit", menu=QuiterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-CRM", command=NewCRM)
tkadd(newStudyMenu,"command", label="Tite-CRM simulator", command=SimCRM)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){tkdestroy(Win_TiTECRM);frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuiterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuiterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TiTECRM))
assign("net.TiTECRM_", tk2notebook(Win_TiTECRM, tabs = c("Input parameters","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TiTECRM_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.TiTECRM_ , "Results"), envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.TiTECRM_ , "Input parameters"), envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2), envir = as.environment(pos))
tkpack.propagate(m2_, FALSE)
}
frameInit()
}
.EWOC=function(pos=1, e)
{
e$EWOC.2 = NULL
e$ResSim = NULL
tclRequire("Tktable")
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.ewoc or file.ewsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
if (filef != "") {
stu=read.table(filef,header=TRUE)
assign("names_Study", paste(stu[1,]), envir = as.environment(pos))
extension<-str_sub(filef,-4)
}
if (extension == "ewoc") {
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res, envir = as.environment(pos))
assign("Study", Study, envir = as.environment(pos))
e$EWOC.2 <- EWOC.2
Open.EWOC()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(include)
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
tkdestroy(include)
}
}
}
}
if (extension == "wsim") {
load(file =paste(paste(names_Study,'ewsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS, envir = as.environment(pos))
tkdestroy(Win_EWOC)
frameInitSIM()
disabled.SimEWOC()
}
}
pending_listing=function()
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
dataa=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(dataa)==0 )
{
msg <- paste("No patient pending",sep="")
tkmessageBox(message=msg)
}
if (nrow(dataa)>=1)
{
assign("tt.pend", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(tt.pend, "+650+400")
assign("tl", tklistbox(tt.pend,height=4,selectmode="single",background="white"),envir = as.environment(pos))
tkgrid(tklabel(tt.pend,text="Select a patient",font=PoliceGenerale))
tkgrid(tl)
numPatP=paste("Patient N_", as.character(dataa$patid),sep="")
for (i in (1:length(numPatP)))
{
tkinsert(tl,"end",numPatP[i])
}
tkselection.set(tl,0)
OK.but <-tkbutton(tt.pend,text=" OK ",command=.include.pending,bg="cornflower blue")
tkgrid(OK.but)
tkfocus(tt.pend)
}
}
.include.pending <- function()
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
data.pinding=Res$PT.data[which(Res$PT.data$pndg==1),]
data.inclus=Res$PT.data[which(Res$PT.data$pndg==0),]
numPatP=as.character(data.pinding$patid)
assign("Choice", as.numeric(numPatP[as.numeric(tkcurselection(tl))+1]),envir = as.environment(pos))
Inc=tktoplevel()
tkwm.geometry(Inc, "+650+400")
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
assign("rbValue.DLT", tclVar(0),envir = as.environment(pos))
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i))))
}
.Sauv2=function(...)
{
DLT <- as.numeric(tclvalue((rbValue.DLT)))
Newpat=data.pinding[which(data.pinding$patid==Choice),]
Newpat$DLT=DLT
Newpat$pndg=0
DATA=rbind(data.inclus,Newpat)
data.ewoc=DATA[c(3,1,2)]
names(data.ewoc)=c('patient', 'dose','tox')
a=dim(data.ewoc)[1]
if (a>1) {data.ewoc$patient<-c(1:a)}
e$EWOC.2 <- bcrm::bcrm(stop=list(nmax=1),data=data.ewoc,p.tox0=Study$DL,simulate=FALSE,
ff=paste(Study$Model),constrain=Study$Constrain,cohort=1,
prior.alpha=list(Study$Prior.c,Study$a,Study$b),target.tox=Study$Target,
pointest=Study$Pointest,method="rjags")
Res$MTD <- e$EWOC.2$ndose[[1]]$ndose
Res$PT.data[which(Res$PT.data$patid==Choice),]$pndg=0
Res$PT.data[which(Res$PT.data$patid==Choice),]$DLT=DLT
EWOC.2 <- e$EWOC.2
save(Res,Study, EWOC.2,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
Res
tkdestroy(Inc)
assign("Res", Res,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if (Res$Pat.included==1){disabled.EWOC()}
}
Inc.Win_EWOC<- tkframe(Inc,relief="groove",borderwidth=3)
Save=tkbutton(Inc.Win_EWOC,text="Validate",width=30,command=.Sauv2,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_EWOC)
tkdestroy (tt.pend)
}
.ReCap=function(...)
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Escalation with overdose control (EWOC) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_EWOC,text="New patient",width=30,command=.include,bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_EWOC,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_EWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
disabled.ReCap=function(...)
{
tkdestroy(Rec.mm0)
tkdestroy(Rec.Win_EWOC)
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
LStudyDL=paste(Study$DL[1])
for( i in 2 : length(Study$DL))
{
LStudyDL=paste(LStudyDL,paste(Study$DL[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(LStudyDL))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Escalation with overdose control (EWOC) "))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Stop==1,"Maximum number of patients to be enrolled in the study","Maximum number of patients by dose level")))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$N_Pat))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="Inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"),font=PoliceGenerale)
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included),font=PoliceGenerale)
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"),font=PoliceGenerale)
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD),font=PoliceGenerale)
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
DATA=Res$PT.data[which(Res$PT.data$pndg==1),]
if (nrow(DATA)==0)
{
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_EWOC,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_EWOC,text="Pending patient",width=30,state="disabled",bg="cornflower blue")
tk2notetab.select(net.EWOC , "Results")
tkgrid(Rec.Win_EWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
if (nrow(DATA)!=0)
{
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_EWOC,text="New patient",width=30, state="disabled",bg="cornflower blue")
Save.pend=tkbutton(Rec.Win_EWOC,text="Pending patient",width=30,command=pending_listing,bg="cornflower blue")
tkgrid(Rec.Win_EWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Save.pend, row=0, column=1)
}
}
.ReCap.Resultat=function(...)
{
Resultsbypatient=function()
{
assign("myRarray1", data.frame(patient=c(1:Res$Pat.included),
dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2]),envir = as.environment(pos))
X=colnames(myRarray1)
myRarray=rbind(X,myRarray1)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat<-tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ResultsbyLevel=function()
{
Sdose=round(e$EWOC.2$ndose[[1]]$est,3)
n.patient=NULL
total.tox=NULL
Mean=round(e$EWOC.2$ndose[[1]]$mean,3)
SD=round(e$EWOC.2$ndose[[1]]$sd,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for (i in 1 : Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Sdose=Sdose, n.patient=n.patient,
total.tox=total.tox, Post.mean=Mean, Post.sd=SD), envir = as.environment(pos))
X=colnames(myRarray2)
myRarray=rbind(X,myRarray2)
a=dim(myRarray)[2]-1
b=dim(myRarray)[1]-1
for (i in (0:b))
for (j in (0:a))
.Tcl(paste("set tclarray(",i,",",j,") ",myRarray[i+1,j+1],sep=""))
Resbypat <- tktoplevel()
t.d <- tkwidget(Resbypat,"table",variable="tclarray",rows=b+1,cols=a+1,titlerows="1",state="disabled",selectmode="extended",colwidth="25",background="white")
tkgrid(t.d, row=2, column=0)
}
ExportRes=function()
{
myRarray1 <- data.frame(patient=c(1:Res$Pat.included),dose_level=Res$PT.data[,1],Toxicity=Res$PT.data[,2])
Sdose=round(e$EWOC.2$ndose[[1]]$est,3)
n.patient=NULL
total.tox=NULL
Mean=round(e$EWOC.2$ndose[[1]]$mean,3)
SD=round(e$EWOC.2$ndose[[1]]$sd,3)
for ( i in 1 : Study$Nb_Dl)
{
res1=sum(Res$PT.data[,1]==i)
n.patient=c(n.patient,res1)
}
for ( i in 1 :Study$Nb_Dl)
{
res0=(Res$PT.data[which(Res$PT.data[,1]==i),])
if (length(res0)==2) {res2=sum(res0[2]==1)} else {res2=sum(res0[,2]==1)}
total.tox=c(total.tox,res2)
}
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Sdose=Sdose, n.patient=n.patient,
total.tox=total.tox, Post.mean=Mean, Post.sd=SD),envir = as.environment(pos))
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
plot(e$EWOC.2)
dev.off()
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=1:3, widths = 14.43)
setColWidths(wb, sheet2, cols=1:6, widths = 14.43)
writeDataTable(wb,sheet1,x=myRarray1)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:6,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Graphic",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Results",width=20,command=Resultsbypatient,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Results",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=Export.Graph,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkgrid(button4, row=7, column=2)
tkconfigure(button4,padx=2)
tkconfigure(Titre.4, font=PoliceTitre)
}
.include=function(...)
{
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
assign("Inc", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for (i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DLT <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rDLT',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=i, text=paste(i),font=PoliceGenerale)))
}
tkgrid(assign(paste('rDLT',2,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.DLT ,value=2, text=paste("pending"))))
.Sauv=function(...)
{
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue((rbValue.DL)))),envir = as.environment(pos))
assign("DLT", c(Res$PT.data[,2],as.numeric(tclvalue((rbValue.DLT)))),envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],Res$Pat.included+1),envir = as.environment(pos))
assign("pndg", as.numeric (c(Res$PT.data[,4],as.numeric(tclvalue((rbValue.DLT)))==2)),envir = as.environment(pos))
Res$PT.data <- data.frame(DL=DL,DLT=DLT,patid=patid,pndg=pndg)
Res$Pat.included <- Res$Pat.included+1
DATA=Res$PT.data[which(Res$PT.data$pndg==0),]
data.ewoc=DATA[c(3,1,2)]
names(data.ewoc)=c('patient', 'dose','tox')
a=dim(data.ewoc)[1]
if (a>1) {data.ewoc$patient<-c(1:a)}
if (nrow(DATA)!=0)
{
e$EWOC.2<- bcrm::bcrm(stop=list(nmax=1),data=data.ewoc, p.tox0=Study$DL,
simulate=FALSE, ff=paste(Study$Model), constrain=Study$Constrain, cohort=1,
prior.alpha=list(Study$Prior.c,Study$a,Study$b),target.tox=Study$Target,
pointest=Study$Pointest,method="rjags")
EWOC.2 <- e$EWOC.2
Res$MTD <- e$EWOC.2$ndose[[1]]$ndose
}
if (nrow(DATA)!=0) {
save(Res,Study,EWOC.2,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))}
else {save(Res,Study,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))}
load(file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if (Study$Stop==1)
{
if(Res$Pat.included==Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
if (Study$Stop==2)
{
x=Res$PT.data[,1]
xunique=unique(x)
for (i in 1 : length(xunique))
{
temp=x[which(x==xunique[i])]
if (length (temp) >= Study$N_Pat)
{
.ReCap.Resultat()
disabled.ReCap()
}
}
}
if (Res$Pat.included==1)
{disabled.EWOC()}
}
Inc.Win_EWOC<- tkframe(Inc,relief="groove",borderwidth=3)
Save=tkbutton(Inc.Win_EWOC,text="Validate",width=30,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_EWOC)
}
Export.Graph=function()
{
plot(e$EWOC.2)
}
NewEWOC=function()
{
tkdestroy(Win_EWOC)
frameInitEWOC()
.Crea.f=function(...)
{
Nb_Niv_Doses <- as.numeric(tclvalue((SliderValue)))
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_Doses!=8)
{
for ( i in (Nb_Niv_Doses+1):8)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
DL=NULL
if (Nb_Dl==2) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {DL=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
Target=as.numeric(tclvalue(tkget((Target))))
model=tclvalue(tkget((model)))
if (model=="Hyperbolic tangent")(Model="ht")
if (model=="Logistic")(Model="logit1")
if (model=="Power")(Model="power")
Prior=tclvalue(tkget((Prior.alpha)))
if (Prior=="Gamma(a,b)")(Prior.c=1)
if (Prior=="Uniform(a,b)")(Prior.c=2)
if (Prior=="Lognormal(a,b)")(Prior.c=3)
a.p=as.numeric(tclvalue(tkget(a)))
b.p=as.numeric(tclvalue(tkget(b)))
pointtest=as.numeric(tclvalue(tkget(pointest)))
Stop=as.numeric(tclvalue(rbValue.SC))
const=as.logical(as.numeric(tclvalue(rbValue.const)))
N_Pat=as.numeric(tclvalue(tkget(NBpat)))
N_pat_Level=as.numeric(tclvalue(tkget(NBpat)))
assign("names_Study", tclvalue(tkget(names.S)),envir = as.environment(pos))
if ((Stop == 1) & (N_Pat <=0)) stop('Number of patients to be enrolled in the study <=0')
if ((Stop == 1) & (N_Pat > 100)) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if ((Stop == 2) & (N_Pat <=0)) stop('Number of patients by dose level <=0')
if ((Stop == 2) & (N_Pat > 20)) cat("\n Warning: Large number of patients by dose level")
if (any(DL <= 0) | any(DL >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(DL, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (Target>0.55) cat("\n Warning: Target DLT rate too high")
if (Target<0.15) cat("\n Warning: Target DLT rate too low")
if ((pointtest < 0) | (pointtest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
assign("Study", list(name=paste(names_Study),Nb_Dl=Nb_Dl,DL=DL,Target=Target,Model=Model,
Stop=Stop,N_Pat=N_Pat,N_pat_Level=N_pat_Level,Prior=Prior,Prior.c=Prior.c,
a.p=a.p,b.p=b.p,Pointest=pointtest, Constrain=const), envir = as.environment(pos))
MTD=max(which(Study$DL==Study$Target),1)
Pat_include=0
PT.data=NULL
assign("Res", list(MTD=MTD,Pat.included=Pat_include,PT.data=PT.data),envir = as.environment(pos))
save(Res,Study,file =paste(paste(names_Study,'ewoc',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(names_Study)
a0=paste('Name of study',paste(names_Study),sep=':')
a1=paste('Method','EWOC',sep=':')
a2='Escalation With Overdose Control (EWOC) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(names_Study),'ewoc', sep='.'))
}
Study.file()
tk2notetab.select(net.EWOC , "Include")
}
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=14)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3), envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
SliderValue=tclVar('8')
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",command=.Crea.f)
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
assign("Target", tkentry(Saisi, width=5),envir = as.environment(pos))
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi) ; rb2 <- tkradiobutton(Saisi)
rbValue.SC <- tclVar(1)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding ",font=PoliceGenerale)
NBpat<-tkentry(Saisi, width=10)
tkgrid(labage, row=5,column=0, sticky="w", columnspan=2)
tkgrid(NBpat, row=5,column=2, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
model <-tk2spinbox(Saisi, values = c("Hyperbolic tangent","Logistic","Power"))
tkgrid(Titre , row=6,column=0, sticky="w")
tkgrid(model, row=6,column=1, sticky="w")
Titre=tklabel(Saisi,text="Prior",font=PoliceGenerale)
Prior.alpha <-tk2spinbox(Saisi, values = c("Gamma(a,b)","Uniform(a,b)","Lognormal(a,b)"))
tkgrid(Titre , row=7,column=0, sticky="w")
tkgrid(Prior.alpha , row=7,column=1, sticky="w")
Titre1=tklabel(Saisi,text="a",font=PoliceGenerale)
Titre2=tklabel(Saisi,text="b",font=PoliceGenerale)
assign("a", tkentry(Saisi, width=5),envir = as.environment(pos))
assign("b", tkentry(Saisi, width=5),envir = as.environment(pos))
tkgrid(Titre1, row=8, column=0, sticky="w")
tkgrid(a, row=8, column=1, sticky="w")
tkgrid(Titre2, row=8, column=2, sticky="w")
tkgrid(b, row=8, column=3, sticky="w")
Titre1=tklabel(Saisi,text="Pointest in [0,0.5]",font=PoliceGenerale)
assign("pointest", tkentry(Saisi, width=5),envir = as.environment(pos))
tkgrid(Titre1, row=10, column=0, sticky="w")
tkgrid(pointest, row=10, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi) ; const2 <- tkradiobutton(Saisi)
rbValue.const <- tclVar(1)
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=11, column=0, sticky="w")
tkgrid(const1, row=11, column=1, sticky="w")
tkgrid(const2, row=12,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
names.S<-tkentry(Saisi, width=20)
tkgrid(labage, row=13,column=0, sticky="w")
tkgrid(names.S, row=13,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study,bg="cornflower blue")
tkgrid(Save.rec, row=1)
}
disabled.EWOC=function()
{
tkdestroy(Saisi)
tkdestroy(m2)
tkdestroy(Saisi.save)
tkdestroy(Rec.mm0)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=14)
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w", columnspan=2)
tkgrid(NBpat, row=5,column=2, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
model <-tk2spinbox(Saisi, values =paste(Study$Model),state="disabled")
tkgrid(Titre , row=6,column=0, sticky="w")
tkgrid(model, row=6,column=1, sticky="w")
Titre=tklabel(Saisi,text="Prior",font=PoliceGenerale)
Prior.alpha <-tk2spinbox(Saisi, values = paste(Study$Prior),state="disabled")
tkgrid(Titre , row=7,column=0, sticky="w")
tkgrid(Prior.alpha , row=7,column=1, sticky="w")
Titre1=tklabel(Saisi,text="a",font=PoliceGenerale)
Titre2=tklabel(Saisi,text="b",font=PoliceGenerale)
a.iter <- tclVar(Study$a.p);b.iter <- tclVar(Study$b.p)
assign("a", tkentry(Saisi, width=5,textvariable=a.iter ,state="disabled"),envir = as.environment(pos))
assign("b", tkentry(Saisi, width=5,textvariable=b.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=8, column=0, sticky="w")
tkgrid(a, row=8, column=1, sticky="w")
tkgrid(Titre2, row=8, column=2, sticky="w")
tkgrid(b, row=8, column=3, sticky="w")
Titre1=tklabel(Saisi,text="Pointest in [0,0.5]",font=PoliceGenerale)
pointest.iter <- tclVar(Study$Pointest)
assign("pointest", tkentry(Saisi, width=5,textvariable=pointest.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=10, column=0, sticky="w")
tkgrid(pointest, row=10, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi, state="disabled") ; const2 <- tkradiobutton(Saisi, state="disabled")
rbValue.const <- tclVar(as.numeric(Study$Constrain))
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=11, column=0, sticky="w")
tkgrid(const1, row=11, column=1, sticky="w")
tkgrid(const2, row=12,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=13,column=0, sticky="w")
tkgrid(names.S, row=13,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled",bg="cornflower blue")
tkgrid(Save.rec, row=1)
.ReCap()
}
Open.EWOC=function()
{
tkdestroy(Win_EWOC)
frameInitEWOC()
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=10)
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
Nb_Niv_Doses <- Study$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$DL[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)) ,sticky="w",row=r,column=1)
}
SliderValue=tclVar(Study$Nb_Dl)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=1, sticky="w")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
Titre=tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(Study$Target)
Target<-tkentry(Saisi, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Titre=tklabel(Saisi,text="Stopping rules",font=PoliceGenerale)
rb1 <- tkradiobutton(Saisi,state="disabled") ; rb2 <- tkradiobutton(Saisi,state="disabled")
rbValue.SC <- tclVar(Study$Stop)
tkconfigure(rb1,variable=rbValue.SC,value=1, text="Maximum number of patients to be enrolled in the study",font=PoliceGenerale)
tkconfigure(rb2,variable=rbValue.SC,value=2, text="Maximum number of patients by dose level",font=PoliceGenerale)
tkgrid(Titre, row=3, column=0, sticky="w")
tkgrid(rb1, row=3, column=1, sticky="w", columnspan=3)
tkgrid(rb2, row=4,column=1, sticky="w", columnspan=3)
labage<-tklabel(Saisi, text="Number of patients corresponding",font=PoliceGenerale)
NP<- tclVar(Study$N_Pat)
NBpat<-tkentry(Saisi, width=10,textvariable=NP,state="disabled")
tkgrid(labage, row=5,column=0, sticky="w", columnspan=2)
tkgrid(NBpat, row=5,column=2, sticky="w")
Titre=tklabel(Saisi,text="Model",font=PoliceGenerale)
model <-tk2spinbox(Saisi, values =paste(Study$Model),state="disabled")
tkgrid(Titre , row=6,column=0, sticky="w")
tkgrid(model, row=6,column=1, sticky="w")
Titre=tklabel(Saisi,text="Prior",font=PoliceGenerale)
Prior.alpha <-tk2spinbox(Saisi, values = paste(Study$Prior),state="disabled")
tkgrid(Titre , row=7,column=0, sticky="w")
tkgrid(Prior.alpha , row=7,column=1, sticky="w")
Titre1=tklabel(Saisi,text="a",font=PoliceGenerale)
Titre2=tklabel(Saisi,text="b",font=PoliceGenerale)
a.iter <- tclVar(Study$a.p);b.iter <- tclVar(Study$b.p)
assign("a", tkentry(Saisi, width=5,textvariable=a.iter ,state="disabled"),envir = as.environment(pos))
assign("b", tkentry(Saisi, width=5,textvariable=b.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=8, column=0, sticky="w")
tkgrid(a, row=8, column=1, sticky="w")
tkgrid(Titre2, row=8, column=2, sticky="w")
tkgrid(b, row=8, column=3, sticky="w")
Titre1=tklabel(Saisi,text="Pointest in [0,0.5]",font=PoliceGenerale)
pointest.iter <- tclVar(Study$Pointest)
assign("pointest", tkentry(Saisi, width=5,textvariable=pointest.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Titre1, row=10, column=0, sticky="w")
tkgrid(pointest, row=10, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi, state="disabled") ; const2 <- tkradiobutton(Saisi, state="disabled")
rbValue.const <-tclVar(as.numeric(Study$Constrain))
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=11, column=0, sticky="w")
tkgrid(const1, row=11, column=1, sticky="w")
tkgrid(const2, row=12,column=1, sticky="w")
labage<-tklabel(Saisi, text="Names of study:",font=PoliceGenerale)
Nam<- tclVar(Study$name)
names.S<-tkentry(Saisi, width=20,textvariable=Nam,state="disabled")
tkgrid(labage, row=13,column=0, sticky="w")
tkgrid(names.S, row=13,column=1, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=20,state="disabled")
tkgrid(Save.rec, row=37, column=1, columnspan=2, rowspan=2)
.ReCap()
.ReCap.Resultat()
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
pdf(paste(filef_,"pdf",sep="."))
plot(e$ResSim2)
dev.off()
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','EWOC',sep=':')
a2='Escalation With Overdose Control (EWOC) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'ewsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'ewsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
Res.print.sim=function() {
n.average <- mean(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.min <- min(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.max <- max(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
assign("n.res", cbind(n.average,n.min,n.max),envir = as.environment(pos))
rec <- sapply(e$ResSim, function(i) {
i$ndose[[length(i$ndose)]]$ndose
})
rec.tab <- prop.table(table(factor(rec, levels = 1:length(e$ResSim[[1]]$tox))))
exp <- sapply(e$ResSim, function(i) {
(i$tox + i$notox)/sum(i$tox + i$notox)
})
exp.tab <- apply(exp, 1, mean)
assign("tab.dose", signif(rbind(exp.tab, rec.tab), 3),envir = as.environment(pos))
tox.cutpoints = NULL
if (is.null(tox.cutpoints)) {
tox.cutpoints <- seq(0, 1, by = 0.2)
} else {
tox.cutpoints <- unique(c(0, tox.cutpoints, 1))
}
assign("exp.tox", signif(prop.table(table(cut(unlist(sapply(e$ResSim, function(i) {
rep(i$truep, (i$tox + i$notox))
}, simplify = FALSE)), tox.cutpoints, include.lowest = T))),2),envir = as.environment(pos))
tox. <- sapply(e$ResSim, function(i) {
(i$tox)
})
assign("tox.tab", apply(tox., 1, mean),envir = as.environment(pos))
}
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
Res.print.sim()
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(tab.dose[2,1],3))
ToxRes=paste(round(tox.tab[1],3))
LevelRes=paste(round(tab.dose[1,1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(tab.dose[2,i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(tab.dose[1,i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(tox.tab[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(ifelse(StudyS$Model=="ht","Hyperbolic tangent",ifelse(StudyS$Model=="logit1","Logistic","Power"))))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size: mean [min,max]"))
aff_7.1<-tklabel(Rec.fr,text=paste(paste(paste(n.res[1]),"[",n.res[2]),",",n.res[3],"]"))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
e$ResSim2 <- e$ResSim
e$ResSim2[[1]]$sdose <- round(e$ResSim[[1]]$sdose,3)
PlotBut=tkbutton(Rec.save_ ,text="Graphic",width=20,command=function(){plot(e$ResSim2)},bg="cornflower blue")
tkgrid(PlotBut, row=1)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(tab.dose[2,],3),
round(tab.dose[1,],3),round(tox.tab,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
disabled.SimEWOC=function()
{
.RecapSimB=function()
{
Res.print.sim = function() {
n.average <- mean(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.min <- min(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
n.max <- max(sapply(e$ResSim, function(i) {
dim(i$data)[1]
}))
assign("n.res", cbind(n.average,n.min,n.max),envir = as.environment(pos))
rec <- sapply(e$ResSim, function(i) {
i$ndose[[length(i$ndose)]]$ndose
})
rec.tab <- prop.table(table(factor(rec, levels = 1:length(e$ResSim[[1]]$tox))))
exp <- sapply(e$ResSim, function(i) {
(i$tox + i$notox)/sum(i$tox + i$notox)
})
exp.tab <- apply(exp, 1, mean)
assign("tab.dose", signif(rbind(exp.tab, rec.tab), 3),envir = as.environment(pos))
tox.cutpoints = NULL
if (is.null(tox.cutpoints)) {
tox.cutpoints <- seq(0, 1, by = 0.2)
} else {
tox.cutpoints <- unique(c(0, tox.cutpoints, 1))
}
assign("exp.tox", signif(prop.table(table(cut(unlist(sapply(e$ResSim, function(i) {
rep(i$truep, (i$tox + i$notox))
}, simplify = FALSE)), tox.cutpoints, include.lowest = T))),2),envir = as.environment(pos))
tox. <- sapply(e$ResSim, function(i) {
(i$tox)
})
assign("tox.tab", apply(tox., 1, mean),envir = as.environment(pos))
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
Res.print.sim()
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(tab.dose[2,1],3))
ToxRes=paste(round(tox.tab[1],3))
LevelRes=paste(round(tab.dose[1,1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(tab.dose[2,i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(tab.dose[1,i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(tox.tab[i],3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(ifelse(StudyS$Model=="ht","Hyperbolic tangent",ifelse(StudyS$Model=="logit1","Logistic","Power"))))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size: mean [min,max]"))
aff_7.1<-tklabel(Rec.fr,text=paste(paste(paste(n.res[1]),"[",n.res[2]),",",n.res[3],"]"))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=13, column=1, sticky="w")
tkgrid(aff_8.1, row=13, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=14, column=1, sticky="w")
tkgrid(aff_9.1, row=14, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=15, column=1, sticky="w")
tkgrid(aff_10.1, row=15, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
e$ResSim2 <- e$ResSim
e$ResSim2[[1]]$sdose<-round(e$ResSim[[1]]$sdose,3)
PlotBut=tkbutton(Rec.save_ ,text="Graphic",width=20,command=function(){plot(e$ResSim2)},bg="cornflower blue")
tkgrid(PlotBut, row=1)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(tab.dose[2,],3),
round(tab.dose[1,],3),round(tox.tab,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=8)
Nb_Niv_Doses <- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0,columnspan=4, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=3, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0,columnspan=3, sticky="w")
tkgrid(Target_, row=2, column=3, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0,columnspan=3, sticky="w")
tkgrid(Nsim_, row=4,column=3, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$X0)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0,columnspan=3, sticky="w")
tkgrid(X0_, row=5,column=3, sticky="w")
if (StudyS$Model=="ht")(model="Hyperbolic tangent")
if (StudyS$Model=="logit1")(model="Logistic")
if (StudyS$Model=="power")(model="Power")
if (StudyS$Prior.a==1)(prior.a="Gamma(a,b)")
if (StudyS$Prior.a==2)(prior.a="Uniform(a,b)")
if (StudyS$Prior.a==3)(prior.a="Lognormal(a,b)")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
Model_ <-tk2spinbox(Saisi_, values = paste(model),state="disabled")
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=2,columnspan=3, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=7,column=0,columnspan=4, sticky="w")
tkgrid(Seed_, row=7,column=4, sticky="w")
Tstop_=tklabel(Saisi_,text="Stopping rule",font=PoliceGenerale)
rbstop.1_ <- tkradiobutton(Saisi_,state="disabled") ; rbstop.2_ <- tkradiobutton(Saisi_,state="disabled")
if (!is.null(StudyS$Nmax)){rbstop.M_ <- tclVar(1)}
if (!is.null(StudyS$Nmtd)){rbstop.M_ <- tclVar(2)}
tkconfigure(rbstop.1_,variable=rbstop.M_,value=1, text="Maximum sample size",font=PoliceGenerale)
tkconfigure(rbstop.2_,variable=rbstop.M_,value=2, text="Maximum number of patients treated at final MTD",font=PoliceGenerale)
tkgrid(Tstop_, row=8,column=0,columnspan=3, sticky="w")
tkgrid(rbstop.1_, row=8,column=3,columnspan=3, sticky="w")
tkgrid(rbstop.2_, row=9,column=3,columnspan=5, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients corresponding",font=PoliceGenerale)
if (!is.null(StudyS$Nmax)){n.iter <- tclVar(StudyS$Nmax)}
if (!is.null(StudyS$Nmtd)){n.iter <- tclVar(StudyS$Nmtd)}
assign("N_", tkentry(Saisi_,width=5,textvariable=n.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Tnum_, row=10, column=0,columnspan=4, sticky="w")
tkgrid(N_, row=10, column=4, sticky="w")
Tpriora_=tklabel(Saisi_,text="Prior Alpha",font=PoliceGenerale)
Prior.alpha_ <-tk2spinbox(Saisi_, values =paste(prior.a),state="disabled")
tkgrid(Tpriora_ , row=11,column=0,columnspan=2, sticky="w")
tkgrid(Prior.alpha_ , row=11,column=2,columnspan=3, sticky="w")
Ta_=tklabel(Saisi_,text="a",font=PoliceGenerale)
Tb_=tklabel(Saisi_,text="b",font=PoliceGenerale)
na <- tclVar(StudyS$a)
nb <- tclVar(StudyS$b)
assign("a_", tkentry(Saisi_, width=5,textvariable=na ,state="disabled"),envir = as.environment(pos))
assign("b_", tkentry(Saisi_, width=5,textvariable=nb ,state="disabled"),envir = as.environment(pos))
tkgrid(Ta_, row=12, column=0, sticky="w")
tkgrid(a_, row=12, column=1, sticky="w")
tkgrid(Tb_, row=12, column=2, sticky="w")
tkgrid(b_, row=12, column=3, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0,0.5]",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Pointest)
assign("pointest_", tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled"),envir = as.environment(pos))
tkgrid(Tpoint_, row=13, column=0,columnspan=2, sticky="w")
tkgrid(pointest_, row=13, column=2, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ; const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=14, column=0, sticky="w")
tkgrid(const1_, row=14, column=1, sticky="w")
tkgrid(const2_, row=15,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=16,column=0,columnspan=2, sticky="w")
tkgrid(names.S_, row=16,column=2,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimEWOC=function()
{
tkdestroy(Win_EWOC)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_<-as.numeric(tclvalue((SliderValue_)))
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
}
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
prior=NULL
true=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))
true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))}
seed=1
target=as.numeric(tclvalue(tkget((Target_))))
nmax=NULL
nmtd=NULL
Stopr=as.numeric(tclvalue((rbstop.M_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
Model=tclvalue(tkget((Model_)))
if (Model=="Hyperbolic tangent")(model="ht")
if (Model=="Logistic")(model="logit1")
if (Model=="Power")(model="power")
Prior=tclvalue(tkget((Prior.alpha_)))
if (Prior=="Gamma(a,b)")(Prior.a=1)
if (Prior=="Uniform(a,b)")(Prior.a=2)
if (Prior=="Lognormal(a,b)")(Prior.a=3)
a.p=as.numeric(tclvalue(tkget(a_)))
b.p=as.numeric(tclvalue(tkget(b_)))
pointest=as.numeric(tclvalue(tkget(pointest_)))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
seed=as.numeric(tclvalue(tkget((Seed_))))
assign("Names_Study", tclvalue(tkget(names.S_)),envir = as.environment(pos))
if (Stopr == 1) {nmax=as.numeric(tclvalue(tkget(N_)))}
if (Stopr == 2) {nmtd=as.numeric(tclvalue(tkget(N_)))}
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (Stopr == 1) {
if (nmax <=0) stop('Number of patients to be enrolled <=0')
if (nmax > 100) cat("\n Warning: Number of patients to be enrolled > 100")
}
if (Stopr == 2) {
if (nmtd <= 0) stop('Number of patients treated at final MTD <=0')
if (nmtd > 20) cat("\n Warning: Number of patients treated at final MTD > 20")
}
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if ((pointest < 0) | (pointest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("StudyS", list(Name=paste(Names_Study),Nb_Dl=Nb_Dl,True=true,Prior=prior,Target=target,
Model=model,Prior.a=Prior.a,a=a.p,b=b.p,Nmax=nmax,Nmtd=nmtd,Pointest=pointest,
Nsim=nsim,X0=x0,Seed=seed, Constrain=Const),envir = as.environment(pos))
if (res.users == 1) { cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim<- bcrm::bcrm(stop=list(nmax=StudyS$Nmax,nmtd=StudyS$Nmtd),p.tox0=StudyS$Prior,
truep=StudyS$True,ff=StudyS$Model, target.tox=StudyS$Target, cohort=1,
prior.alpha=list(StudyS$Prior.a,StudyS$a,StudyS$b), pointest=StudyS$Pointest,
start=StudyS$X0,simulate=TRUE,nsims=StudyS$Nsim,method="rjags",quietly=TRUE,
constrain=StudyS$Constrain, seed=StudyS$Seed)
.RecapSim()
tk2notetab.select(net.EWOC_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_=tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0,columnspan=4, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=3, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
assign("Target_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Titre_, row=2, column=0,columnspan=3, sticky="w")
tkgrid(Target_, row=2, column=3, sticky="w")
l<-tklabel(Saisi_,text=" ")
tkgrid(l, row=2, column=3)
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0,columnspan=3, sticky="w")
tkgrid(Nsim_, row=4,column=3, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0,columnspan=3, sticky="w")
tkgrid(X0_, row=5,column=3, sticky="w")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
Model_ <-tk2spinbox(Saisi_, values = c("Hyperbolic tangent","Logistic","Power"))
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=2,columnspan=3, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=7,column=0,columnspan=4, sticky="w")
tkgrid(Seed_, row=7,column=4, sticky="w")
Tstop_=tklabel(Saisi_,text="Stopping rule",font=PoliceGenerale)
rbstop.1_ <- tkradiobutton(Saisi_) ; rbstop.2_ <- tkradiobutton(Saisi_)
rbstop.M_ <- tclVar(1)
tkconfigure(rbstop.1_,variable=rbstop.M_,value=1, text="Maximum sample size",font=PoliceGenerale)
tkconfigure(rbstop.2_,variable=rbstop.M_,value=2, text="Maximum number of patients treated at final MTD",font=PoliceGenerale)
tkgrid(Tstop_, row=8,column=0,columnspan=3, sticky="w")
tkgrid(rbstop.1_, row=8,column=3,columnspan=3, sticky="w")
tkgrid(rbstop.2_, row=9,column=3,columnspan=5, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients corresponding",font=PoliceGenerale)
assign("N_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Tnum_, row=10, column=0,columnspan=4, sticky="w")
tkgrid(N_, row=10, column=4, sticky="w")
Tpriora_=tklabel(Saisi_,text="Prior Alpha",font=PoliceGenerale)
Prior.alpha_ <-tk2spinbox(Saisi_, values = c("Gamma(a,b)","Uniform(a,b)","Lognormal(a,b)"))
tkgrid(Tpriora_ , row=11,column=0,columnspan=2, sticky="w")
tkgrid(Prior.alpha_ , row=11,column=2,columnspan=3, sticky="w")
Ta_=tklabel(Saisi_,text="a",font=PoliceGenerale)
Tb_=tklabel(Saisi_,text="b",font=PoliceGenerale)
assign("a_", tkentry(Saisi_, width=5),envir = as.environment(pos));
assign("b_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Ta_, row=12, column=0, sticky="w")
tkgrid(a_, row=12, column=1, sticky="w")
tkgrid(Tb_, row=12, column=2, sticky="w")
tkgrid(b_, row=12, column=3, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0,0.5]",font=PoliceGenerale)
assign("pointest_", tkentry(Saisi_, width=5),envir = as.environment(pos))
tkgrid(Tpoint_, row=13, column=0,columnspan=2, sticky="w")
tkgrid(pointest_, row=13, column=2, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ; const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=14, column=0, sticky="w")
tkgrid(const1_, row=14, column=1, sticky="w")
tkgrid(const2_, row=15,column=1, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=16,column=0,columnspan=2, sticky="w")
tkgrid(names.S_, row=16,column=2,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive EWOC or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Escalade With Overdose Control Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://cran.r-project.org/package=bcrm", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit=function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_EWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_EWOC, "630x550")
tkwm.geometry(Win_EWOC, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_EWOC, ilogo)
tktitle(Win_EWOC) <- "GUI EWOC"
tkpack.propagate(Win_EWOC, FALSE)
topMenu <- tk2menu(Win_EWOC)
tkconfigure(Win_EWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive EWOC", command=NewEWOC)
tkadd(newStudyMenu,"command", label="EWOC simulator", command=SimEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_EWOC); frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_EWOC))
}
frameInitEWOC=function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_EWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_EWOC, "630x610")
tkwm.geometry(Win_EWOC, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_EWOC, ilogo)
tktitle(Win_EWOC) <- "GUI EWOC"
tkpack.propagate(Win_EWOC, FALSE)
names_Study=''
topMenu <- tk2menu(Win_EWOC)
tkconfigure(Win_EWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive EWOC", command=NewEWOC)
tkadd(newStudyMenu,"command", label="EWOC simulator", command=SimEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_EWOC); frameInit()} )
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_EWOC))
assign("net.EWOC", tk2notebook(Win_EWOC, tabs = c("Input parameters","Include","Results")),envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.EWOC , fill = "both", expand = 1)
assign("include", tk2notetab(net.EWOC , "Include"),envir = as.environment(pos))
tkpack.propagate(include, FALSE)
assign("Resultas", tk2notetab(net.EWOC , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("Required", tk2notetab(net.EWOC , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("Saisi", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Saisi.save", tkframe(Required,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
assign("m2", tkframe(Required,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
assign("Rec.Win_EWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.Win_EWOC, row=9, column=2, rowspan=16)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, columnspan=3, rowspan=16)
assign("halfwidthPrior", NULL,envir = as.environment(pos))
assign("nuPrior", NULL,envir = as.environment(pos))
assign("etatPrior", FALSE,envir = as.environment(pos))
}
frameInitSIM=function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_EWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_EWOC, "765x700")
tkwm.geometry(Win_EWOC, "+460+100")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_EWOC, ilogo)
tktitle(Win_EWOC) <- "GUI EWOC"
tkpack.propagate(Win_EWOC, FALSE)
names_Study=''
topMenu <- tk2menu(Win_EWOC)
tkconfigure(Win_EWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive EWOC", command=NewEWOC)
tkadd(newStudyMenu,"command", label="EWOC simulator", command=SimEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_EWOC); frameInit()})
tkadd(AideMenu,"command", label="Help R (manual)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_EWOC))
assign("net.EWOC_", tk2notebook(Win_EWOC, tabs = c("Input parameters","Results")),envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.EWOC_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.EWOC_ , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.EWOC_ , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=0, columnspan=2, rowspan=7)
}
frameInit()
}
.TEWOC=function(pos=1, e)
{
e$TEWOC. = NULL
e$ResSim = NULL
tclRequire("Tktable")
loads <- function()
{
loads.infos <- tkmessageBox(title = "Data loading Infos",
message = "Select a file.tewoc or file.tewsim", icon = "info", type = "ok")
filef <- tclvalue(tkgetOpenFile())
if (filef != "") {
stu=read.table(filef,header=TRUE)
assign("Names_Study", paste(stu[1,]),envir = as.environment(pos))
extension<-str_sub(filef,-6)
}
if (extension == ".tewoc") {
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
e$TEWOC. <- TEWOC.
disabled.TEWOC()
.ReCap.Resultat()
if (Res$Pat.included >= Study$Npat)
{ cat('Maximal number of patients reached out', "\n")
disabled.Recap()
}else { .ReCap() }
}
if (extension == "tewsim") {
load(file =paste(paste(Names_Study,'tewsim',sep='-'),'RData',sep='.'),envir = as.environment(pos))
e$ResSim <- ResSim
assign("StudyS", StudyS,envir = as.environment(pos))
tkdestroy(Win_TEWOC)
frameInitSIM()
disabled.SimTEWOC()
}
}
ExcellExport=function (dframe=NULL) {
if (!is.data.frame(dframe)) {stop("The argument must be a data.frame object")}
filef_ <- tclvalue(tkgetSaveFile())
if (filef_ != "") {
filesave=paste(filef_,"xlsx",sep=".")
wb_ <- createWorkbook()
sheet1_ <- addWorksheet(wb_, sheetName="Simulation")
style_ <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb_, sheet1_, cols=c(1,2,3,4,5), widths = 13.43)
writeDataTable(wb_,sheet1_,x=dframe)
addStyle(wb_,sheet1_,style_,cols=1:5,rows=1)
saveWorkbook(wb_, filesave, overwrite = T)
}
}
.include=function(...)
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
assign("mess", tkmessageBox(message = "Do you want to enter mutiple patient data at the same time?",
icon = "question", type = "yesno", default = "yes"),envir = as.environment(pos))
if (tclvalue(mess)=="no") {
assign("Inc", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(mm)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.DL <- tclVar(Res$MTD)
for (i in 1: Study$Nb_Dl)
{
tkgrid(assign(paste('rDL',i,sep=''),tkradiobutton(mm,variable=rbValue.DL ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Inc.mm1", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Inc.mm1)
Titre <- tklabel(Inc.mm1,text="DLT",font=PoliceGenerale)
tkgrid(Titre, row=0, columnspan=2)
rbValue.tox <- tclVar(0)
for ( i in 0: 1)
{
tkgrid(assign(paste('rtox',i,sep=''),tkradiobutton(Inc.mm1,variable=rbValue.tox ,value=i, text=paste(i),font=PoliceGenerale)))
}
assign("Fup", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(Fup)
TitreFup <- tklabel(Fup,text="Follow-up Time")
tkgrid(TitreFup, row=0, columnspan=2)
val = tclVar(Study$Obs.wind)
assign("Followup", tkentry(Fup,textvariable=val, width=10),envir = as.environment(pos))
tkgrid(Followup)
} else if (tclvalue(mess)=="yes") {
Police <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
assign("Inc", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(Inc, "+550+270")
tkwm.geometry(Inc, "505x230")
assign("mm", tkframe(Inc,relief="groove",borderwidth=3),envir = as.environment(pos))
tkgrid(mm)
Rules <- tklabel(mm,text="The data must be separated with comma (ex: 1,1,2)",font=Police)
tkgrid(Rules, row=0, columnspan=2)
space0 <- tklabel(mm, text=" ")
tkgrid(space0, row=1, column=0)
Titre <- tklabel(mm,text="Treated dose level",font=PoliceGenerale)
tkgrid(Titre, row=2, column=0)
level. <- tkentry(mm, width=60)
tkgrid(level., row=2, column=1)
space1 <- tklabel(mm, text=" ")
tkgrid(space1, row=3, column=0)
Ttox <- tklabel(mm,text="DLT (0=No, 1=Yes)",font=PoliceGenerale)
tkgrid(Ttox, row=4, column=0)
tox. <- tkentry(mm, width=60)
tkgrid(tox., row=4, column=1)
space2 <- tklabel(mm, text=" ")
tkgrid(space2, row=5, column=0)
TFup <- tklabel(mm,text=paste("Follow-up","<=",Study$Obs.wind,sep=' '),
font=PoliceGenerale)
tkgrid(TFup, row=6, column=0)
Fup. <- tkentry(mm, width=60)
tkgrid(Fup., row=6, column=1)
}
.Sauv=function(...)
{
if (tclvalue(mess)=="yes") {
assign("DL", c(Res$PT.data[,1],as.numeric(c(do.call("cbind",strsplit(tclvalue(tkget(level.)),","))))),envir = as.environment(pos))
assign("tox", c(Res$PT.data[,2],as.numeric(c(do.call("cbind",strsplit(tclvalue(tkget(tox.)),","))))),envir = as.environment(pos))
assign("fup",c(Res$PT.data[,4],as.numeric(c(do.call("cbind",strsplit(tclvalue(tkget(Fup.)),","))))),envir = as.environment(pos))
assign("patid", c(Res$PT.data[,3],c((Res$Pat.included+1):(length(DL)))),envir = as.environment(pos))
Res$Pat.included=length(patid)
} else {
assign("DL", c(Res$PT.data[,1],as.numeric(tclvalue(rbValue.DL))),envir = as.environment(pos))
assign("tox", c(Res$PT.data[,2],as.numeric(tclvalue(rbValue.tox))),envir = as.environment(pos))
Res$Pat.included<-Res$Pat.included+1
assign("patid", c(Res$PT.data[,3],Res$Pat.included),envir = as.environment(pos))
assign("fup", c(Res$PT.data[,4],as.numeric(tclvalue(tkget(Followup)))),envir = as.environment(pos))
}
Res$PT.data <- data.frame(DL=DL,Tox=tox,patid=patid,Fup=fup)
e$TEWOC. <- .titeewoc(prior=Study$Prior, target=Study$Target, tox=Res$PT.data[,2],
level=Res$PT.data[,1], followup=Res$PT.data[,4], obswin=Study$Obs.wind,
pointest=Study$Pointest, method="rjags", model=Study$Model, intcpt=Study$Intcpt,
p.dist=Study$P.dist, p1=Study$P1, p2=Study$P2, alphap=Study$Alphap, constrain= Study$Constrain)
Res$MTD <- e$TEWOC.$dose.rec
TEWOC. <- e$TEWOC.
save(Res,Study,TEWOC.,file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
tkdestroy(Inc)
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
if(Res$Pat.included==Study$Npat)
{
disabled.Recap()
}
if(Res$Pat.included > Study$Npat)
{
disabled.Recap()
Save.infos <- tkmessageBox(title = "Stopping rule",
message = "More patients than expected were included",
icon = "warning", type = "ok")
}
}
Inc.Win_EWOC<- tkframe(Inc,relief="groove",borderwidth=3)
Save=tkbutton(Inc.Win_EWOC,text="Validate",width=10,command=.Sauv,bg="cornflower blue")
tkgrid(Save)
tkgrid(Inc.Win_EWOC)
}
.ReCap=function(...)
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
priorp=paste(Study$Prior[1])
for( i in 2 : length(Study$Prior))
{
priorp=paste(priorp,paste(Study$Prior[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(priorp))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Time-to-Event Escalation With Overdose Control (Tite-EWOC)"))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste("Sample size"))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$Npat))
affiche_10.0<-tklabel(Rec.mm0,text=paste("Observation window "))
affiche_10.1<-tklabel(Rec.mm0,text=paste(Study$Obs.wind))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
tkgrid(affiche_10.0, row=11, column=1, sticky="w")
tkgrid(affiche_10.1, row=11, column=2, sticky="w")
tkconfigure(affiche_10.0, font=Policeligne )
tkconfigure(affiche_10.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="red")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="red")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_TEWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_TEWOC,text="New patient",width=30,command=.include,bg="cornflower blue")
Modif=tkbutton(Rec.Win_TEWOC,text="Modif patient data",width=30,command=.modif.data.patient,bg="cornflower blue")
tkgrid(Rec.Win_TEWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
tkgrid(Modif, row=0, column=1)
}
.modif.data.patient= function (...)
{
.modif.data=function (...)
{
assign("id.modif", as.numeric(tkcurselection(tlm)) + 1, envir = as.environment(pos))
tkdestroy(tt.modif)
m.data=Res$PT.data[id.modif,]
win.m <- tktoplevel()
dlt. <- tclVar(m.data[,2])
level. <- tclVar(m.data[,1])
followup. <- tclVar(m.data[,4])
lab.id. <- tklabel(win.m,text=paste("Patient N_",id.modif),font=PoliceGenerale)
tkgrid(lab.id., row=0, columnspan=2)
lab.level. <- tklabel(win.m,text=paste("Dose level"),font=PoliceGenerale)
tkgrid(lab.level., row=1, columnspan=2)
assign("win.level", tk2entry(win.m, width = "3", textvariable = level.),envir = as.environment(pos))
tkgrid(win.level,row=1,column=2)
lab.dlt. <- tklabel(win.m,text=paste("DLT (1= 'Yes', 0='No')"),font=PoliceGenerale)
tkgrid(lab.dlt., row=3, columnspan=2)
assign("win.dlt", tk2entry(win.m, width = "3", textvariable = dlt.),envir = as.environment(pos))
tkgrid(win.dlt,row=3,column=2)
lab.fup. <- tklabel(win.m,text=paste("follow-up","<=",Study$Obs.wind),font=PoliceGenerale)
tkgrid(lab.fup., row=5, columnspan=2)
assign("win.fup", tk2entry(win.m, width = "3", textvariable = followup.),envir = as.environment(pos))
tkgrid(win.fup,row=5,column=2)
onOK <- function() {
new.dlt. <- as.numeric(tclvalue(tkget(win.dlt)))
new.level <- as.numeric(tclvalue(tkget(win.level)))
new.fup <- as.numeric(tclvalue(tkget(win.fup)))
Res$PT.data[id.modif,c(2,1,4)] <- c(new.dlt.,new.level,new.fup)
e$TEWOC. <- .titeewoc(prior=Study$Prior, target=Study$Target, tox=Res$PT.data[,2],
level=Res$PT.data[,1], followup=Res$PT.data[,4], obswin=Study$Obs.wind,
pointest=Study$Pointest, method="rjags", model=Study$Model, intcpt=Study$Intcpt,
p.dist=Study$P.dist, p1=Study$P1, p2=Study$P2, alphap=Study$Alphap, constrain= Study$Constrain)
Res$MTD <- e$TEWOC.$dose.rec
TEWOC. <- e$TEWOC.
save(Res,Study,TEWOC.,file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'))
tkdestroy(win.m)
assign("Res", Res,envir = as.environment(pos))
assign("Study", Study,envir = as.environment(pos))
.ReCap()
.ReCap.Resultat()
}
win.OK <-tkbutton(win.m, text = "OK", width = 10, command = onOK, bg="cornflower blue")
tkgrid(win.OK)
}
assign("m.data", Res$PT.data,envir = as.environment(pos))
if (is.null(m.data))
{
msg <- paste("No patient included",sep="")
tkmessageBox(message=msg)
}
if (!is.null(m.data))
{
if (nrow(m.data)>=1)
{
assign("tt.modif", tktoplevel(),envir = as.environment(pos))
tkwm.geometry(tt.modif, "+650+400")
assign("tlm", tklistbox(tt.modif,height=nrow(m.data)+1,selectmode="single",background="white"),envir = as.environment(pos))
tkgrid(tklabel(tt.modif,text="Select a patient",font=PoliceGenerale))
tkgrid(tlm)
patlist=paste(" Patient N_", as.character(m.data$patid),sep="")
for (i in (1:length(patlist)))
{
tkinsert(tlm,"end",patlist[i])
}
tkselection.set(tlm,0)
OK.but <-tkbutton(tt.modif,text=" OK ",command=.modif.data,bg="cornflower blue")
tkgrid(OK.but)
}
}
}
disabled.Recap=function(...)
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
priorp=paste(Study$Prior[1])
for( i in 2 : length(Study$Prior))
{
priorp=paste(priorp,paste(Study$Prior[i]),sep=" , ")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
assign("Rec.mm0", tkframe(include, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.mm0, row=0, column=0, rowspan=16)
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=0, column=0)
NS<-tklabel(Rec.mm0,text=Study$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=2, column=0)
Titre1<-tklabel(Rec.mm0,text="Characteristics of the study")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
affiche_4.0<-tklabel(Rec.mm0,text=paste("Number of dose levels "))
affiche_4.1<-tklabel(Rec.mm0,text=paste(Study$Nb_Dl))
affiche_2.0<-tklabel(Rec.mm0,text=paste("Initial estimated probabilities " ))
affiche_2.1<-tklabel(Rec.mm0,text=paste(priorp))
affiche_3.0<-tklabel(Rec.mm0,text=paste("Target DLT rate"))
affiche_3.1<-tklabel(Rec.mm0,text=paste(Study$Target))
affiche_1.0<-tklabel(Rec.mm0,text=paste("Method "))
affiche_1.1<-tklabel(Rec.mm0,text=paste("Time-to-Event Escalation With Overdose Control (Tite-EWOC)"))
affiche_5.0<-tklabel(Rec.mm0,text=paste("Statistical model "))
affiche_5.1<-tklabel(Rec.mm0,text=paste(ifelse(Study$Model=="ht","Hyperbolic tangent",ifelse(Study$Model=="logit1","Logistic","Power"))))
affiche_6.0<-tklabel(Rec.mm0,text=paste("Stopping rules "))
affiche_6.1<-tklabel(Rec.mm0,text=paste("Sample size"))
affiche_7.0<-tklabel(Rec.mm0,text=paste("Maximal number of patients "))
affiche_7.1<-tklabel(Rec.mm0,text=paste(Study$Npat))
affiche_10.0<-tklabel(Rec.mm0,text=paste("Observation window "))
affiche_10.1<-tklabel(Rec.mm0,text=paste(Study$Obs.wind))
tkgrid(affiche_1.0, row=4, column=1, sticky="w")
tkgrid(affiche_1.1, row=4, column=2, sticky="w")
tkconfigure(affiche_1.0, font=Policeligne)
tkconfigure(affiche_1.1, font=Policeligne , foreground="blue")
tkgrid(affiche_2.0, row=5, column=1, sticky="w")
tkgrid(affiche_2.1, row=5, column=2, sticky="w")
tkconfigure(affiche_2.0, font=Policeligne)
tkconfigure(affiche_2.1, font=Policeligne , foreground="blue")
tkgrid(affiche_3.0, row=6, column=1, sticky="w")
tkgrid(affiche_3.1, row=6, column=2, sticky="w")
tkconfigure(affiche_3.0, font=Policeligne )
tkconfigure(affiche_3.1, font=Policeligne , foreground="blue")
tkgrid(affiche_4.0, row=7, column=1, sticky="w")
tkgrid(affiche_4.1, row=7, column=2, sticky="w")
tkconfigure(affiche_4.0, font=Policeligne )
tkconfigure(affiche_4.1, font=Policeligne , foreground="blue")
tkgrid(affiche_5.0, row=8, column=1, sticky="w")
tkgrid(affiche_5.1, row=8, column=2,sticky="w")
tkconfigure(affiche_5.0, font=Policeligne )
tkconfigure(affiche_5.1, font=Policeligne , foreground="blue")
tkgrid(affiche_6.0, row=9, column=1, sticky="w")
tkgrid(affiche_6.1, row=9, column=2, sticky="w")
tkconfigure(affiche_6.0, font=Policeligne)
tkconfigure(affiche_6.1, font=Policeligne , foreground="blue")
tkgrid(affiche_7.0, row=10, column=1, sticky="w")
tkgrid(affiche_7.1, row=10, column=2, sticky="w")
tkconfigure(affiche_7.0, font=Policeligne )
tkconfigure(affiche_7.1, font=Policeligne , foreground="blue")
tkgrid(affiche_10.0, row=11, column=1, sticky="w")
tkgrid(affiche_10.1, row=11, column=2, sticky="w")
tkconfigure(affiche_10.0, font=Policeligne )
tkconfigure(affiche_10.1, font=Policeligne , foreground="blue")
Titre2<-tklabel(Rec.mm0,text="inclusion")
tkgrid(Titre2, row=12, column=1,sticky="w")
tkconfigure(Titre2, font=PoliceTitre)
affiche_8.0<-tklabel(Rec.mm0,text=paste("Number of patients included:"))
affiche_8.1<-tklabel(Rec.mm0,text=paste(Res$Pat.included))
affiche_9.0<-tklabel(Rec.mm0,text=paste("Estimated MTD:"))
affiche_9.1<-tklabel(Rec.mm0,text=paste(Res$MTD))
tkgrid(affiche_8.0, row=13, column=1, sticky="w")
tkgrid(affiche_8.1, row=13, column=2, sticky="w")
tkconfigure(affiche_8.0, font=Policeligne )
tkconfigure(affiche_8.1, font=Policeligne , foreground="blue")
tkgrid(affiche_9.0, row=14, column=1,sticky="w")
tkgrid(affiche_9.1, row=14, column=2,sticky="w")
tkconfigure(affiche_9.0, font=Policeligne)
tkconfigure(affiche_9.1, font=Policeligne , foreground="blue")
l<-tklabel(Rec.mm0,text="")
tkgrid(l, row=15, column=0)
assign("Rec.Win_TEWOC", tkframe(include,relief="groove",borderwidth=3),envir = as.environment(pos))
Save=tkbutton(Rec.Win_TEWOC,text="New patient",width=30,state="disabled",bg="cornflower blue")
tkgrid(Rec.Win_TEWOC, row=16, column=0)
tkgrid(Save, row=0, column=0)
Modif=tkbutton(Rec.Win_TEWOC,text="Modif patient data",width=30,state="disabled",bg="cornflower blue")
tkgrid(Modif, row=0, column=1)
}
.ReCap.Resultat <- function ()
{
load(file =paste(paste(Names_Study,'tewoc',sep='-'),'RData',sep='.'),envir = as.environment(pos))
ResultsPat <- function() {
myRarray. <- data.frame(dose_level=Res$PT.data[,1],
Toxicity=Res$PT.data[,2],Follow_up=Res$PT.data[,4])
rownames(myRarray.) <- c(1:dim(myRarray.)[1])
rownames(myRarray.) <- paste0("Pat N_ ",rownames(myRarray.))
tclarray. <- tclArrayVar(myRarray.)
print.tclArrayVar(tclarray.)
}
ResultsbyLevel<- function() {
prior=e$TEWOC.$prior
n.patient=e$TEWOC.$nb.pat.level
total.tox=e$TEWOC.$nb.tox.level
m.weight=round(e$TEWOC.$weights.m.level,3)
quantiles=signif(t(e$TEWOC.$quantiles.ptox[c(1,3,5),]),3)
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=prior, Nb.patient=n.patient,
Total.tox=total.tox,mean.weight=m.weight,q=quantiles),envir = as.environment(pos))
rownames(myRarray2) <- c(1:dim(myRarray2)[1])
rownames(myRarray2) <- paste0("dose ",rownames(myRarray2))
tclarray2 <- tclArrayVar(myRarray2)
print.tclArrayVar(tclarray2)
}
ExportRes <- function() {
filef <- tclvalue(tkgetSaveFile())
if (filef != "") {
filesave=paste(filef,"xlsx",sep=".")
pdf(paste(filef,"pdf",sep="."))
n=length(Res$PT.data[,1])
x=c(1:n)
y=Res$PT.data[,1]
z=Res$PT.data[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
dev.off()
ggsave(plot=.plot.titeewoc(e$TEWOC.) , filename=paste(paste(filef,"boxplot",sep=""),"pdf",sep="."))
myRarray. <- data.frame(dose_level=Res$PT.data[,1],
Toxicity=Res$PT.data[,2],Follow_up=Res$PT.data[,4])
rownames(myRarray.) <- c(1:dim(myRarray.)[1])
rownames(myRarray.) <- paste0("Pat N_ ",rownames(myRarray.))
prior=e$TEWOC.$prior
n.patient=e$TEWOC.$nb.pat.level
total.tox=e$TEWOC.$nb.tox.level
m.weight=round(e$TEWOC.$weights.m.level,3)
quantiles=signif(t(e$TEWOC.$quantiles.ptox[c(1,3,5),]),3)
assign("myRarray2", data.frame(Level=c(1:Study$Nb_Dl),Prior=prior, Nb.patient=n.patient,
Total.tox=total.tox,mean.weight=m.weight,q=quantiles), envir = as.environment(pos))
rownames(myRarray2) <- c(1:dim(myRarray2)[1])
rownames(myRarray2) <- paste0("dose ",rownames(myRarray2))
wb <- createWorkbook()
sheet1 <- addWorksheet(wb, sheetName="By patients")
sheet2 <- addWorksheet(wb, sheetName="By dose level")
style <- createStyle(fontSize = 12, fontColour = "black",
textDecoration = c("bold", "italic", "underline"),
halign = "center", valign = "center", border = "Bottom",
fgFill = "gray")
setColWidths(wb, sheet1, cols=1:3, widths = 14.43)
setColWidths(wb, sheet2, cols=1:8, widths = 14.43)
writeDataTable(wb,sheet1,x=myRarray.)
writeDataTable(wb,sheet2,x=myRarray2)
addStyle(wb,sheet1,style,cols=1:3,rows=1)
addStyle(wb,sheet2,style,cols=1:8,rows=1)
saveWorkbook(wb, filesave, overwrite = T)
}
}
GrapheResults = function(...)
{
n=length(Res$PT.data[,1])
x=c(1:n)
y=Res$PT.data[,1]
z=Res$PT.data[,2]
Data=data.frame(x=x,y=y,z=z)
plot(x,y,pch=16,cex=2,col=(z+1),type='b',axes=FALSE,xlab="Patient number",ylab='Dose Level',main="Patients, Dose level and toxicity")
axis(1, lwd = 2)
axis(side=2,1:8, lwd = 2)
legend("bottomright",inset = c(0.0, -0.19), lwd=c(2.5,2.5),legend=c("Non Toxicity","Toxicity"), col = c(1,2), pch = 16,cex=0.8,xpd = NA)
}
GrapheGG = function()
{
print(.plot.titeewoc(e$TEWOC.))
}
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=9)
l1<-tklabel(Resultas,text="")
l2<-tklabel(Resultas,text="")
l3<-tklabel(Resultas,text="")
l4<-tklabel(Resultas,text="")
l5<-tklabel(Resultas,text="")
Titre.1=tklabel(Resultas,text="Patient Summary",font=PoliceTitre)
Titre.2=tklabel(Resultas,text="Dose level Summary",font=PoliceTitre)
Titre.3=tklabel(Resultas,text="Toxicity plot",font=PoliceTitre)
Titre.4=tklabel(Resultas,text="Toxicity Prob boxplot",font=PoliceTitre)
Titre.5=tklabel(Resultas,text="Export results",font=PoliceTitre)
button1=tkbutton(Resultas ,text="Summary",width=20,command=ResultsPat,bg="cornflower blue")
button2=tkbutton(Resultas ,text="Summary",width=20,command=ResultsbyLevel,bg="cornflower blue")
button3=tkbutton(Resultas ,text="Graphic",width=20,command=GrapheResults,bg="cornflower blue")
button4=tkbutton(Resultas ,text="Graphic",width=20,command=GrapheGG,bg="cornflower blue")
button5=tkbutton(Resultas ,text="Export",width=20,command=ExportRes,bg="cornflower blue")
tkgrid(l1, row=0, column=0)
tkgrid(Titre.1, row=1, column=1, sticky="w")
tkconfigure(Titre.1, font=PoliceTitre)
tkgrid(button1, row=1, column=2)
tkgrid(l2, row=2, column=1)
tkgrid(Titre.2, row=3, column=1, sticky="w")
tkconfigure(Titre.2, font=PoliceTitre)
tkgrid(button2, row=3, column=2)
tkgrid(l3, row=4, column=1)
tkgrid(Titre.3, row=5, column=1, sticky="w")
tkconfigure(Titre.3, font=PoliceTitre)
tkgrid(button3, row=5, column=2)
tkgrid(l4, row=6, column=1)
tkgrid(Titre.4, row=7, column=1, sticky="w")
tkconfigure(Titre.4, font=PoliceTitre)
tkgrid(button4, row=7, column=2)
tkgrid(l5, row=8, column=1)
tkgrid(Titre.5, row=9, column=1, sticky="w")
tkgrid(button5, row=9, column=2)
tkconfigure(button5,padx=2)
tkconfigure(Titre.5, font=PoliceTitre)
}
disabled.TEWOC=function()
{
tkdestroy(Win_TEWOC)
frameInitTEWOC()
Nb_Niv_Doses <- Study$Nb_Dl
assign("m2", tkframe(Required, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
assign("Saisi", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=15)
assign("Saisi.save", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (Study$Prior[i])
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=4)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=5)
}
SliderValue<-tclVar(Nb_Niv_Doses)
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=2, sticky="w")
Titre <-tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar (Study$Target)
Target <-tkentry(Saisi, width=5, textvariable=n.iter, state="disabled")
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Tmod = tklabel(Saisi,text="Model",font=PoliceGenerale)
n.iter <- switch (Study$Model, ht="Hyperbolique tangent",
power="Power", logit1="1-Logistic")
Model <- tk2spinbox(Saisi, values = c( n.iter,""),width=19, state="disabled")
tkgrid(Tmod , row=6,column=0, sticky="w")
tkgrid(Model, row=6,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
intcpt <- if (is.null(Study$Intcpt))
{ c("NA") }
else { Study$Intcpt}
n.intcpt <- tclVar(intcpt)
assign("intcpt.", tkentry(Saisi, width=10, textvariable=n.intcpt, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
Tstop=tklabel(Saisi,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop, row=7,column=0,columnspan=4, sticky="w")
Tnum=tklabel(Saisi,text="Number of patients corresponding",font=PoliceGenerale)
n.iter <- tclVar(Study$Npat)
N <- tkentry(Saisi, width=5, textvariable=n.iter, state="disabled")
tkgrid(Tnum, row=8, column=0, columnspan=2, sticky="w")
tkgrid(N, row=8, column=2, sticky="w")
Tpdist = tklabel(Saisi,text="Prior alpha dist. ",font=PoliceGenerale)
n.iter <- switch (Study$P.dist, unif="Uniform [p1,p2]",
gamma="Gamma (p1,p2)")
Pdist <- tk2spinbox(Saisi, values = c(n.iter,""), width=15, state="disabled")
tkgrid(Tpdist , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist, row=9,column=1, sticky="w")
Talpha=tklabel(Saisi,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1=tklabel(Saisi,text="p1",font=PoliceGenerale)
Tp2=tklabel(Saisi,text="p2",font=PoliceGenerale)
n.al <- tclVar(Study$Alphap); n.p1 <- tclVar(Study$P1)
n.p2 <- tclVar(Study$P2)
alpha<-tkentry(Saisi, width=7, textvariable=n.al, state="disabled")
p1<-tkentry(Saisi, width=7, textvariable=n.p1, state="disabled")
p2<-tkentry(Saisi, width=7, textvariable=n.p2, state="disabled")
tkgrid(Tp1, row=10, column=0, sticky="w")
tkgrid(p1, row=10, column=1, sticky="w")
tkgrid(Tp2, row=10, column=2, sticky="w")
tkgrid(p2, row=10, column=3, sticky="w")
tkgrid(Talpha, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha, row=11, column=2, sticky="w")
Tpoint = tklabel(Saisi, text="Pointest in [0, 0.5]",font=PoliceGenerale)
n. <- tclVar(Study$Pointest)
point <- tkentry(Saisi, width=10, textvariable=n., state="disabled")
tkgrid(Tpoint, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point, row=12, column=1, sticky="w")
Titrec =tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi, state="disabled") ;
const2 <- tkradiobutton(Saisi, state="disabled")
rbValue.const <- tclVar(as.numeric(Study$Constrain))
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1, row=12, column=4, sticky="w")
tkgrid(const2, row=13,column=4, sticky="w")
Twind<-tklabel(Saisi, text="Observation window",font=PoliceGenerale)
n.obs <- tclVar(Study$Obs.wind)
Wind<-tkentry(Saisi, width=10, textvariable=n.obs, state="disabled")
tkgrid(Twind, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind, row=13,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(Study$Name)
names.S<-tkentry(Saisi, width=18, textvariable=Nam_, state="disabled")
tkgrid(labage, row=14, column=0, sticky="w")
tkgrid(names.S, row=14, column=1,columnspan=2, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,state="disabled", bg="cornflower blue")
tkgrid(Save.rec, row=1)
}
NewTEWOC=function()
{
tkdestroy(Win_TEWOC)
frameInitTEWOC()
.Crea.f=function(...)
{
Nb_Niv_Doses <- as.numeric(tclvalue((SliderValue)))
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8),envir = as.environment(pos)),row=r,column=1)
}
if( Nb_Niv_Doses!=8)
{
for ( i in (Nb_Niv_Doses+1):8)
{
r=17 + i
tkgrid(assign(paste('lab',i,sep=''),tklabel(m2, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=0)
tkgrid(assign(paste('val',i,sep=''),tkentry(m2, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=1)
}
}
}
disp.int=function()
{
if (!(tclvalue(tkget(Model))=="1-Logistic"))
{
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(Saisi, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
else {
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale)
assign("intcpt.", tkentry(Saisi, width=10),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
}
}
.Sauvgarde.Study=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue))
prior=NULL
if (Nb_Dl==2) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))))}
if (Nb_Dl==3) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))))}
if (Nb_Dl==4) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))))}
if (Nb_Dl==5) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))))}
if (Nb_Dl==6) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))))}
if (Nb_Dl==7) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),
as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),as.numeric(tclvalue(tkget(val7))))}
if (Nb_Dl==8) {prior=c(as.numeric(tclvalue(tkget(val1))),as.numeric(tclvalue(tkget(val2))),as.numeric(tclvalue(tkget(val3))),
as.numeric(tclvalue(tkget(val4))),as.numeric(tclvalue(tkget(val5))),as.numeric(tclvalue(tkget(val6))),
as.numeric(tclvalue(tkget(val7))),as.numeric(tclvalue(tkget(val8))))}
npat=NULL
alphap=1
target=as.numeric(tclvalue(tkget((Target))))
pointest=as.numeric(tclvalue(tkget(point)))
const=as.logical(as.numeric(tclvalue((rbValue.const))))
model.=tclvalue(tkget(Model))
intcpt=NULL
if (model. == "Hyperbolic tangent") model = "ht"
if (model. == "1-Logistic") {model = "logit1"; intcpt=as.numeric(tclvalue(tkget(intcpt.)))}
if (model. == "Power") model = "power"
pdist.=tclvalue(tkget(Pdist))
if (pdist. == "Uniform [p1,p2]") pdist = "unif"
if (pdist. == "Gamma (p1,p2)") pdist = "gamma"
npat=as.numeric(tclvalue(tkget((N))))
alphap=as.numeric(tclvalue(tkget((alpha))))
p2=as.numeric(tclvalue(tkget((p2))))
p1=as.numeric(tclvalue(tkget((p1))))
twind=as.numeric(tclvalue(tkget(Wind)))
assign("Names_Study", tclvalue(tkget(names.S)),envir = as.environment(pos))
if (npat <=0) stop('Number of patients to be enrolled in the study <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled in the study > 100")
if (twind <= 0 ) stop('Observation window incorrect')
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if ((pointest < 0) | (pointest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
assign("Study", list(Name=paste(Names_Study), Nb_Dl=Nb_Dl, Prior=prior, Target=target,
P.dist=pdist, P1=p1, P2=p2, Model=model, Alphap=alphap, Intcpt=intcpt,
Method="rjags", Npat=npat, Pointest=pointest, Obs.wind=twind, Constrain=const),
envir = as.environment(pos))
MTD <- max(which.min(abs(Study$Prior-Study$Target)),1)
Pat_Include <- 0
PT.data <- NULL
assign ("Res", list(MTD=MTD,Pat.included=Pat_Include,PT.data=PT.data,Obs.wind=Study$Obs.wind),
envir = as.environment(pos))
save(Res,Study,file =paste(paste(Study$Name,'tewoc',sep='-'),'RData',sep='.'))
.ReCap()
Study.file=function()
{
a00=paste(Study$Name)
a0=paste('Name of study',paste(Study$Name),sep=':')
a1=paste('Method','Tite-EWOC',sep=':')
a2='Time-to-Event Escalation With Overdose Control (Tite-EWOC) for Phase I Clinical Trials'
datee <- paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(Study$Name),'tewoc', sep='.'))
}
Study.file()
tk2notetab.select(net.TEWOC , "Include")
}
assign("Saisi", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
tkgrid(Saisi, row=1, column=0, columnspan=4, rowspan=15)
assign("Saisi.save", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi.save, FALSE)
tkgrid(Saisi.save , row=27, column=0, sticky="se")
assign("m2", tkframe(Required, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=8)
SliderValue<-tclVar('8')
slider_Nb_DL <- tkscale(Saisi, from=2, to=8,showvalue=T, variable=SliderValue, resolution=1, orient="horiz",command=.Crea.f)
tkgrid(tklabel(Saisi,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL , row=1,column=2, sticky="w")
Titre <-tklabel(Saisi,text="Target DLT rate",font=PoliceGenerale)
Target <-tkentry(Saisi, width=5)
tkgrid(Titre, row=2, column=0, sticky="w")
tkgrid(Target, row=2, column=1, sticky="w")
Tmod = tklabel(Saisi,text="Model",font=PoliceGenerale)
Model <- tk2spinbox(Saisi, values = c("Hyperbolic tangent","1-Logistic","Power"),width=17, command=disp.int)
tkgrid(Tmod , row=6,column=0, sticky="w")
tkgrid(Model, row=6,column=1, sticky="w")
Tintcpt.<-tklabel(Saisi, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt.", tkentry(Saisi, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt., row=6,column=2, sticky="w")
tkgrid(intcpt., row=6,column=3, sticky="w")
Tstop=tklabel(Saisi,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop, row=7,column=0,columnspan=4, sticky="w")
Tnum=tklabel(Saisi,text="Number of patients corresponding",font=PoliceGenerale)
N <- tkentry(Saisi, width=5)
tkgrid(Tnum, row=8, column=0, columnspan=2, sticky="w")
tkgrid(N, row=8, column=2, sticky="w")
Tpdist = tklabel(Saisi,text="Prior alpha dist. ",font=PoliceGenerale)
Pdist <- tk2spinbox(Saisi, values = c("Uniform [p1,p2]","Gamma (p1,p2)"),width=15)
tkgrid(Tpdist , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist, row=9,column=1, sticky="w")
Talpha=tklabel(Saisi,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1=tklabel(Saisi,text="p1",font=PoliceGenerale)
Tp2=tklabel(Saisi,text="p2",font=PoliceGenerale)
alpha<-tkentry(Saisi, width=7)
p1<-tkentry(Saisi, width=7);p2<-tkentry(Saisi, width=7)
tkgrid(Tp1, row=10, column=0, sticky="w")
tkgrid(p1, row=10, column=1, sticky="w")
tkgrid(Tp2, row=10, column=2, sticky="w")
tkgrid(p2, row=10, column=3, sticky="w")
tkgrid(Talpha, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha, row=11, column=2, sticky="w")
Tpoint = tklabel(Saisi, text="Pointest in [0, 0.5]",font=PoliceGenerale)
point <- tkentry(Saisi, width=10)
tkgrid(Tpoint, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point, row=12, column=1, sticky="w")
Titrec=tklabel(Saisi,text="Dose skipping constraint",font=PoliceGenerale)
const1 <- tkradiobutton(Saisi) ;
const2 <- tkradiobutton(Saisi)
rbValue.const <- tclVar(1)
tkconfigure(const1,variable=rbValue.const,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2,variable=rbValue.const,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1, row=12, column=4, sticky="w")
tkgrid(const2, row=13,column=4, sticky="w")
Twind<-tklabel(Saisi, text="Observation window",font=PoliceGenerale)
Wind<-tkentry(Saisi, width=10)
tkgrid(Twind, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind, row=13,column=1, sticky="w")
labage<-tklabel(Saisi, text="Name of study ",font=PoliceGenerale)
names.S<-tkentry(Saisi, width=18)
tkgrid(labage, row=14, column=0, sticky="w")
tkgrid(names.S, row=14, column=1,columnspan=2, sticky="w")
Save.rec=tkbutton(Saisi.save ,text="Save study",width=25,command=.Sauvgarde.Study, bg="cornflower blue")
tkgrid(Save.rec, row=1)
}
.RecapSim=function()
{
.Save_sim=function()
{
Study.file=function()
{
a00=paste(StudyS$Name)
a0=paste('Name of study',paste(StudyS$Name),sep=':')
a1=paste('Method','Tite-EWOC',sep=':')
a2='Time-to-Event Escalation With Overdose Control (Tite-EWOC) for Phase I Clinical Trials'
datee<-paste(format(Sys.time(), "%A %d %B %Y"))
a3=paste('Date of creation',datee)
Data=data.frame(c(a00,a0,a1,a2,a3))
write.table(Data,paste(paste(StudyS$Name),'tewsim', sep='.'))
}
Study.file()
ResSim <- e$ResSim
save(ResSim,StudyS,file =paste(paste(StudyS$Name,'tewsim',sep='-'),'RData',sep='.'))
Save.infos <- tkmessageBox(title = "Data storage Infos",
message = "File saved in the current working directory of the R proces", icon = "info", type = "ok")
}
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(e$ResSim$pct.dose.rec[1],3))
ToxRes=paste(round(e$ResSim$nb.tox.level[1]/e$ResSim$nsim,3))
LevelRes=paste(round(e$ResSim$pat.level[1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$pct.dose.rec[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$pat.level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$nb.tox.level[i]/e$ResSim$nsim,3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
model <- switch (StudyS$Model, ht="hyperbolique tangent",
power="Power", logit1="1-logistic")
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-to-Event Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(model))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$samplesize))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Mean inter-patient arrival time"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Tmean.arrival))
aff_13.0<-tklabel(Rec.fr,text=paste("Observation window"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Obs.wind))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(e$ResSim$pct.dose.rec,3),
round(e$ResSim$pat.level,3),round(e$ResSim$nb.tox.level,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,command=.Save_sim,bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
disabled.SimTEWOC=function()
{
.RecapSimB=function()
{
PoliceEtude <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=15)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=12)
Policeligne <- tkfont.create(family="calibri",underline=FALSE, size=11)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
assign("Rec.fr", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.fr, row=0, column=0, rowspan=20)
PriorRes=paste(round(StudyS$Prior[1],3))
TrueRes=paste(round(StudyS$True[1],3))
MTDRes=paste(round(e$ResSim$pct.dose.rec[1],3))
ToxRes=paste(round(e$ResSim$nb.tox.level[1]/e$ResSim$nsim,3))
LevelRes=paste(round(e$ResSim$pat.level[1],3))
for( i in 2 : length(StudyS$Prior))
{
PriorRes=paste(PriorRes,paste(round(StudyS$Prior[i],3)),sep=", ")
TrueRes=paste(TrueRes,paste(round(StudyS$True[i],3)),sep=", ")
MTDRes=paste(MTDRes,paste(round(e$ResSim$pct.dose.rec[i],3)),sep=", ")
LevelRes=paste(LevelRes,paste(round(e$ResSim$pat.level[i],3)),sep=", ")
ToxRes=paste(ToxRes,paste(round(e$ResSim$nb.tox.level[i]/e$ResSim$nsim,3)),sep=", ")
}
NS<-tklabel(Rec.fr,text=StudyS$Name,bg="cornflower blue")
tkgrid(NS, row=1, column=1, sticky="w")
tkconfigure(NS, font=PoliceEtude, foreground="white")
Titre1<-tklabel(Rec.fr,text="Results of the simulation")
tkgrid(Titre1, row=3, column=1)
tkconfigure(Titre1, font=PoliceTitre)
model <- switch (StudyS$Model, ht="hyperbolique tangent",
power="Power", logit1="1-logistic")
aff_5.0<-tklabel(Rec.fr,text=paste("Number of dose levels "))
aff_5.1<-tklabel(Rec.fr,text=paste(StudyS$Nb_Dl))
aff_3.0<-tklabel(Rec.fr,text=paste("Prior toxicity rates" ))
aff_3.1<-tklabel(Rec.fr,text=paste(PriorRes))
aff_2.0<-tklabel(Rec.fr,text=paste("True toxicity rates" ))
aff_2.1<-tklabel(Rec.fr,text=paste(TrueRes))
aff_4.0<-tklabel(Rec.fr,text=paste("Target DLT rate"))
aff_4.1<-tklabel(Rec.fr,text=paste(StudyS$Target))
aff_1.0<-tklabel(Rec.fr,text=paste("Method "))
aff_1.1<-tklabel(Rec.fr,text=paste("Time-to-Event Escalation With Overdose Control "))
aff_6.0<-tklabel(Rec.fr,text=paste("Statistical model "))
aff_6.1<-tklabel(Rec.fr,text=paste(model))
aff_8.0<-tklabel(Rec.fr,text=paste("% recommendation MTD"))
aff_8.1<-tklabel(Rec.fr,text=paste(MTDRes))
aff_7.0<-tklabel(Rec.fr,text=paste("Sample size"))
aff_7.1<-tklabel(Rec.fr,text=paste(e$ResSim$samplesize))
aff_9.0<-tklabel(Rec.fr,text=paste("Percentage of patients treated by dose level"))
aff_9.1<-tklabel(Rec.fr,text=paste(LevelRes))
aff_10.0<-tklabel(Rec.fr,text=paste("Average number of toxicities observed by dose level"))
aff_10.1<-tklabel(Rec.fr,text=paste(ToxRes))
aff_11.0<-tklabel(Rec.fr,text=paste("Number of simulations"))
aff_11.1<-tklabel(Rec.fr,text=paste(StudyS$Nsim))
aff_12.0<-tklabel(Rec.fr,text=paste("Mean inter-patient arrival time"))
aff_12.1<-tklabel(Rec.fr,text=paste(StudyS$Tmean.arrival))
aff_13.0<-tklabel(Rec.fr,text=paste("Observation window"))
aff_13.1<-tklabel(Rec.fr,text=paste(StudyS$Obs.wind))
tkgrid(aff_1.0, row=4, column=1, sticky="w")
tkgrid(aff_1.1, row=4, column=2, sticky="w")
tkconfigure(aff_1.0, font=Policeligne)
tkconfigure(aff_1.1, font=Policeligne , foreground="blue")
tkgrid(aff_2.0, row=6, column=1, sticky="w")
tkgrid(aff_2.1, row=6, column=2, sticky="w")
tkconfigure(aff_2.0, font=Policeligne)
tkconfigure(aff_2.1, font=Policeligne , foreground="blue")
tkgrid(aff_3.0, row=7, column=1, sticky="w")
tkgrid(aff_3.1, row=7, column=2, sticky="w")
tkconfigure(aff_3.0, font=Policeligne )
tkconfigure(aff_3.1, font=Policeligne , foreground="blue")
tkgrid(aff_4.0, row=8, column=1, sticky="w")
tkgrid(aff_4.1, row=8, column=2, sticky="w")
tkconfigure(aff_4.0, font=Policeligne )
tkconfigure(aff_4.1, font=Policeligne , foreground="blue")
tkgrid(aff_5.0, row=9, column=1, sticky="w")
tkgrid(aff_5.1, row=9, column=2,sticky="w")
tkconfigure(aff_5.0, font=Policeligne )
tkconfigure(aff_5.1, font=Policeligne , foreground="blue")
tkgrid(aff_6.0, row=10, column=1, sticky="w")
tkgrid(aff_6.1, row=10, column=2, sticky="w")
tkconfigure(aff_6.0, font=Policeligne)
tkconfigure(aff_6.1, font=Policeligne , foreground="blue")
tkgrid(aff_7.0, row=11, column=1, sticky="w")
tkgrid(aff_7.1, row=11, column=2, sticky="w")
tkconfigure(aff_7.0, font=Policeligne )
tkconfigure(aff_7.1, font=Policeligne , foreground="blue")
tkgrid(aff_11.0, row=12, column=1, sticky="w")
tkgrid(aff_11.1, row=12, column=2, sticky="w")
tkconfigure(aff_11.0, font=Policeligne )
tkconfigure(aff_11.1, font=Policeligne , foreground="blue")
tkgrid(aff_12.0, row=13, column=1, sticky="w")
tkgrid(aff_12.1, row=13, column=2, sticky="w")
tkconfigure(aff_12.0, font=Policeligne )
tkconfigure(aff_12.1, font=Policeligne , foreground="blue")
tkgrid(aff_13.0, row=14, column=1, sticky="w")
tkgrid(aff_13.1, row=14, column=2, sticky="w")
tkconfigure(aff_13.0, font=Policeligne )
tkconfigure(aff_13.1, font=Policeligne , foreground="blue")
tkgrid(aff_8.0, row=15, column=1, sticky="w")
tkgrid(aff_8.1, row=15, column=2, sticky="w")
tkconfigure(aff_8.0, font=Policeligne )
tkconfigure(aff_8.1, font=Policeligne , foreground="blue")
tkgrid(aff_9.0, row=16, column=1, sticky="w")
tkgrid(aff_9.1, row=16, column=2, sticky="w")
tkconfigure(aff_9.0, font=Policeligne )
tkconfigure(aff_9.1, font=Policeligne , foreground="blue")
tkgrid(aff_10.0, row=17, column=1, sticky="w")
tkgrid(aff_10.1, row=17, column=2, sticky="w")
tkconfigure(aff_10.0, font=Policeligne )
tkconfigure(aff_10.1, font=Policeligne , foreground="blue")
assign("Rec.save_", tkframe(Resultas_, borderwidth=3),envir = as.environment(pos))
tkgrid(Rec.save_, row=20, column=0)
l<-tklabel(Rec.save_,text="")
tkgrid(l, row=2)
ResExp_<-data.frame(cbind(StudyS$True,StudyS$Prior,round(e$ResSim$pct.dose.rec,3),
round(e$ResSim$pat.level,3),round(e$ResSim$nb.tox.level/e$ResSim$nsim,3)))
colnames(ResExp_)<-c("True tox.", "Prior tox." ,"MTD dist.(%)",
"(%)patient","Av. tox. ")
WordExp_=tkbutton(Rec.save_,text="Export Results",width=15,
command=function()ExcellExport(dframe=ResExp_),bg="cornflower blue")
tkgrid(WordExp_, row=3)
blank<-tklabel(Rec.save_,text=" ")
tkgrid(blank, row=4)
SaveSim_=tkbutton(Rec.save_,text="Save results",width=15,state="disabled",bg="cornflower blue")
tkgrid(SaveSim_, row=5)
}
tkdestroy(Saisi_)
tkdestroy(m2_)
tkdestroy(Run_)
assign("Saisi_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
assign("m2_", tkframe(Required_, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=1, columnspan=4, rowspan=7)
Nb_Niv_Doses <- StudyS$Nb_Dl
for ( i in 1: Nb_Niv_Doses)
{
r=17 + i
n.iter <- tclVar (StudyS$Prior[i])
n.itert<- tclVar (StudyS$True[i])
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8, textvariable=n.itert,state="disabled"),envir = as.environment(pos)),row=r,column=3)
tkgrid(assign(paste('labp',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=4)
tkgrid(assign(paste('valp',i,sep=''),tkentry(m2_, width=8, textvariable=n.iter,state="disabled"),envir = as.environment(pos)),row=r,column=5)
}
SliderValue_=tclVar(StudyS$Nb_Dl)
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",state="disabled")
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=2, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Target)
Target_<-tkentry(Saisi_, width=5,textvariable=n.iter ,state="disabled")
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Nsim)
Nsim_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level level",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Strt.dose)
X0_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
n.iter <- switch (StudyS$Model, ht="Hyperbolique tangent",
power="Power", logit1="1-Logistic")
Model_ <- tk2spinbox(Saisi_, values = c(n.iter,"") ,state="disabled")
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=1, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept", font=PoliceGenerale)
intcpt <- if (is.null(StudyS$Intcpt))
{ c("NA") }
else { StudyS$Intcpt}
n.intcpt <- tclVar(intcpt)
assign("intcpt_", tkentry(Saisi_, width=10,textvariable=n.intcpt, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6,column=2, sticky="w")
tkgrid(intcpt_, row=6,column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop_, row=7,column=0,columnspan=4, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Npat)
N_<-tkentry(Saisi_,width=5,textvariable=n.iter ,state="disabled")
tkgrid(Tnum_, row=8, column=0, sticky="w")
tkgrid(N_, row=8, column=1, sticky="w")
Tpdist_ = tklabel(Saisi_,text="Prior alpha dist. ",font=PoliceGenerale)
n.iter <- switch (StudyS$P.dist, unif="Uniform [p1,p2]",
gamma="Gamma (p1,p2)")
Pdist_ <- tk2spinbox(Saisi_, values = c(n.iter,""), width=15, state="disabled")
tkgrid(Tpdist_ , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist_, row=9,column=1, sticky="w")
Talpha_=tklabel(Saisi_,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1_=tklabel(Saisi_,text="p1",font=PoliceGenerale)
Tp2_=tklabel(Saisi_,text="p2",font=PoliceGenerale)
n.al <- tclVar(StudyS$Alpha); n.p1 <- tclVar(StudyS$P1)
n.p2 <- tclVar(StudyS$P2)
alpha_<-tkentry(Saisi_, width=7, textvariable=n.al, state="disabled")
p1_<-tkentry(Saisi_, width=7, textvariable=n.p1, state="disabled")
p2_<-tkentry(Saisi_, width=7, textvariable=n.p2, state="disabled")
tkgrid(Tp1_, row=10, column=0, sticky="w")
tkgrid(p1_, row=10, column=1, sticky="w")
tkgrid(Tp2_, row=10, column=2, sticky="w")
tkgrid(p2_, row=10, column=3, sticky="w")
tkgrid(Talpha_, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha_, row=11, column=2, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0, 0.5]",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Pointest)
point_<-tkentry(Saisi_, width=10, textvariable=n.iter ,state="disabled")
tkgrid(Tpoint_, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point_, row=12, column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_, state="disabled") ;
const2_ <- tkradiobutton(Saisi_, state="disabled")
rbValue.const_ <- tclVar(as.numeric(StudyS$Constrain))
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1_, row=12, column=4, sticky="w")
tkgrid(const2_, row=13,column=4, sticky="w")
Twind_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Obs.wind)
Wind_<-tkentry(Saisi_,textvariable=n.iter, width=10,state="disabled")
tkgrid(Twind_, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind_, row=13,column=1, sticky="w")
Tparr_<-tklabel(Saisi_, text="Mean inter-patient arrival time",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Tmean.arrival)
Parr_<-tkentry(Saisi_,textvariable=n.iter, width=10,state="disabled")
tkgrid(Tparr_, row=14,column=0,columnspan=3, sticky="w")
tkgrid(Parr_, row=14,column=2, sticky="w")
Tacc_<-tklabel(Saisi_, text="Accrual",font=PoliceGenerale)
Acc_<-tk2spinbox(Saisi_, values = c(StudyS$Accrual),width=7,state="disabled")
tkgrid(Tacc_, row=15,column=0, sticky="w")
tkgrid(Acc_, row=15,column=1, sticky="w")
Ttox_<-tklabel(Saisi_, text="Time until toxicity occurence",font=PoliceGenerale)
n.iter <- switch(StudyS$Toxocc, unif="uniform", exp="exponential")
tox_<-tk2spinbox(Saisi_, values = c(n.iter), width=10, state="disabled")
tkgrid(Ttox_, row=16,column=0,columnspan=3, sticky="w")
tkgrid(tox_, row=16,column=2, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
n.iter <- tclVar(StudyS$Seed)
Seed_<-tkentry(Saisi_, width=10,textvariable=n.iter ,state="disabled")
tkgrid(Tseed_, row=17,column=0,columnspan=2, sticky="w")
tkgrid(Seed_, row=17,column=2, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
Nam_<- tclVar(StudyS$Name)
names.S_<-tkentry(Saisi_, width=20,textvariable=Nam_,state="disabled")
tkgrid(labage_, row=18,column=0, sticky="w")
tkgrid(names.S_, row=18,column=1,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,state="disabled",bg="cornflower blue")
tkgrid(RunSim_, row=1)
.RecapSimB()
}
SimTEWOC=function()
{
tkdestroy(Win_TEWOC)
frameInitSIM()
.Crea.f_=function(...)
{
Nb_Niv_Doses_ <- as.numeric(tclvalue((SliderValue_)))
for ( i in 1: Nb_Niv_Doses_)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=2)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=3)
tkgrid(assign(paste('labp',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale)),row=r,column=4)
tkgrid(assign(paste('valp',i,sep=''),tkentry(m2_, width=8),envir = as.environment(pos)),row=r,column=5)
}
if( Nb_Niv_Doses_!=8)
{
for ( i in (Nb_Niv_Doses_+1):8)
{
r=17 + i
tkgrid(assign(paste('labt',i,sep=''),tklabel(m2_, text=paste('True at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=2)
tkgrid(assign(paste('valt',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=3)
tkgrid(assign(paste('labp',i,sep=''),tklabel(m2_, text=paste('Prior at Level',i,sep=' '),font=PoliceGenerale,state="disabled")),row=r,column=4)
tkgrid(assign(paste('valp',i,sep=''),tkentry(m2_, width=8,state="disabled"),envir = as.environment(pos)),row=r,column=5)
}
}
}
disp.int_=function()
{
if (!(tclvalue(tkget(Model_))=="1-Logistic"))
{
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6,column=2, sticky="w")
tkgrid(intcpt_, row=6,column=3, sticky="w")
}
else {
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale)
assign("intcpt_", tkentry(Saisi_, width=10),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6, column=2, sticky="w")
tkgrid(intcpt_, row=6, column=3, sticky="w")
}
}
.Simulation_=function (...)
{
.Sauvgarde.Study_=function(...)
{
Nb_Dl=as.numeric(tclvalue(SliderValue_))
true=NULL
prior=NULL
if (Nb_Dl==2) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))))}
if (Nb_Dl==3) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))))}
if (Nb_Dl==4) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),as.numeric(tclvalue(tkget(valp4))))}
if (Nb_Dl==5) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))))}
if (Nb_Dl==6) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))),as.numeric(tclvalue(tkget(valp6))))}
if (Nb_Dl==7) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),
as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),as.numeric(tclvalue(tkget(valt7))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),
as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))),as.numeric(tclvalue(tkget(valp6))),as.numeric(tclvalue(tkget(valp7))))}
if (Nb_Dl==8) {true=c(as.numeric(tclvalue(tkget(valt1))),as.numeric(tclvalue(tkget(valt2))),as.numeric(tclvalue(tkget(valt3))),
as.numeric(tclvalue(tkget(valt4))),as.numeric(tclvalue(tkget(valt5))),as.numeric(tclvalue(tkget(valt6))),
as.numeric(tclvalue(tkget(valt7))),as.numeric(tclvalue(tkget(valt8))))
prior=c(as.numeric(tclvalue(tkget(valp1))),as.numeric(tclvalue(tkget(valp2))),as.numeric(tclvalue(tkget(valp3))),
as.numeric(tclvalue(tkget(valp4))),as.numeric(tclvalue(tkget(valp5))),as.numeric(tclvalue(tkget(valp6))),
as.numeric(tclvalue(tkget(valp7))),as.numeric(tclvalue(tkget(valp8))))}
seed=NULL
npat=NULL
alpha=1
target=as.numeric(tclvalue(tkget((Target_))))
pointest=as.numeric(tclvalue(tkget(point_)))
Const=as.logical(as.numeric(tclvalue((rbValue.const_))))
model.=tclvalue(tkget(Model_))
intcpt=NULL
if (model. == "Hyperbolic tangent") model = "ht"
if (model. == "1-Logistic") {model = "logit1"; intcpt=intcpt=as.numeric(tclvalue(tkget(intcpt_)))}
if (model. == "Power") model = "power"
toxocc <- switch(tclvalue(tkget(tox_)), uniform="unif", exponential="exp")
pdist_=tclvalue(tkget(Pdist_))
if (pdist_ == "Uniform [p1,p2]") pdist = "unif"
if (pdist_ == "Gamma (p1,p2)") pdist = "gamma"
accrual=tclvalue(tkget(Acc_))
nsim=as.numeric(tclvalue(tkget((Nsim_))))
x0=as.numeric(tclvalue(tkget((X0_))))
npat=as.numeric(tclvalue(tkget((N_))))
alpha=as.numeric(tclvalue(tkget((alpha_))))
p2=as.numeric(tclvalue(tkget((p2_))))
p1=as.numeric(tclvalue(tkget((p1_))))
twind=as.numeric(tclvalue(tkget(Wind_)))
tparr=as.numeric(tclvalue(tkget(Parr_)))
seed=as.numeric(tclvalue(tkget((Seed_))))
assign("Names_Study", tclvalue(tkget(names.S_)),envir = as.environment(pos))
res.users <- 1
if (target>0.55) cat("\n Warning: Target DLT rate too high")
if (target<0.15) cat("\n Warning: Target DLT rate too low")
if (npat <=0) stop('Number of patients to be enrolled <=0')
if (npat > 100) cat("\n Warning: Number of patients to be enrolled > 100")
if ((x0 <1)|(x0 > Nb_Dl)|(x0%%1 != 0)) stop(paste('Starting dose level incorrect, enter an integer between 1 and',Nb_Dl))
if ((pointest < 0) | (pointest > 0.5)) stop('Pointest parameter must be within [0,0.5]')
if (twind <= 0 ) stop('Observation window incorrect')
if (tparr <= 0 ) stop('Mean inter patient arrival time must be strictly positive')
if (nsim < 100) cat("\n Warning: Low number of simulations")
check_nsim <- function (){
res.users <- 2
while (res.users != 0 & res.users != 1) {
cat("\n Warning: Large number of simulations, continue? y or n")
yn <- readLines(n=1)
if(yn == "y" | yn == "Y" | yn== "yes" | yn == "Yes"){res.users <- 1;}
if(yn == "n" | yn == "N" | yn== "no" | yn == "No"){res.users <- 0;}
}
return(res.users)
}
if (any(prior <= 0) | any(prior >= 1)) stop('Prior probabilities must be within ]0,1[ ')
if (is.unsorted(prior, strictly = TRUE)) stop('Prior probabilities should be monotonically increasing')
if (any(true <= 0) | any(true >= 1)) stop('True probabilities must be within ]0,1[ ')
if (is.unsorted(true, strictly = TRUE)) stop('True probabilities should be monotonically increasing')
if (nsim > 10000) {res.users <- check_nsim()}
assign("StudyS", list(Name=paste(Names_Study),Nb_Dl=Nb_Dl, True=true, Prior=prior,Target=target,
P1=p1, P2=p2, Model=model, Accrual=accrual, Alpha=alpha, P.dist=pdist,
Method="rjags", Npat=npat, Pointest=pointest, Toxocc=toxocc, Intcpt=intcpt, Constrain=Const,
Nsim=nsim, Strt.dose=x0, Obs.wind=twind, Tmean.arrival=tparr, Seed=seed),envir = as.environment(pos))
if(res.users == 1) {
cat("\n Submission in progress... Please wait... ", "\n")
e$ResSim <- .titeewocsim(nsim=StudyS$Nsim, true=StudyS$True, prior=StudyS$Prior, target=StudyS$Target,
obswin = StudyS$Obs.wind, tparr = StudyS$Tmean.arrival, accrual = StudyS$Accrual,
start = StudyS$Strt.dose, samplesize = StudyS$Npat, method = StudyS$Method,
pointest=StudyS$Pointest, model = StudyS$Model, toxocc=StudyS$Toxocc,
constrain = StudyS$Constrain, p1 = StudyS$P1, p2=StudyS$P2, p.dist=StudyS$P.dist,
alphap = StudyS$Alpha, count= FALSE, intcpt=StudyS$Intcpt,
seed=StudyS$Seed, burnin.itr = 2000, production.itr = 2000)
.RecapSim()
tk2notetab.select(net.TEWOC_, "Results")
}
}
.Sauvgarde.Study_()
}
assign("Saisi_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
tkgrid(Saisi_, row=1, column=1, columnspan=4, rowspan=10)
assign("Run_", tkframe(Required_, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
tkgrid(Run_ , row=24, column=6, sticky="e")
SliderValue_ <- tclVar('8')
slider_Nb_DL_ <- tkscale(Saisi_, from=2, to=8,showvalue=T, variable=SliderValue_, resolution=1, orient="horiz",command=.Crea.f_)
tkgrid(tklabel(Saisi_,text="Number of dose levels",font=PoliceGenerale),row=1,column=0, sticky="w")
tkgrid(slider_Nb_DL_ , row=1,column=2, sticky="w")
Titre_=tklabel(Saisi_,text="Target DLT rate",font=PoliceGenerale)
Target_<-tkentry(Saisi_, width=5)
tkgrid(Titre_, row=2, column=0, sticky="w")
tkgrid(Target_, row=2, column=1, sticky="w")
Tnsim_<-tklabel(Saisi_, text="Number of simulations",font=PoliceGenerale)
Nsim_<-tkentry(Saisi_, width=10)
tkgrid(Tnsim_, row=4,column=0, sticky="w")
tkgrid(Nsim_, row=4,column=1, sticky="w")
TX0_<-tklabel(Saisi_, text="Starting dose level",font=PoliceGenerale)
X0_<-tkentry(Saisi_, width=10)
tkgrid(TX0_, row=5,column=0, sticky="w")
tkgrid(X0_, row=5,column=1, sticky="w")
Tmod_=tklabel(Saisi_,text="Model",font=PoliceGenerale)
Model_ <-tk2spinbox(Saisi_, values = c("Hyperbolic tangent","1-Logistic","Power"), command=disp.int_)
tkgrid(Tmod_ , row=6,column=0, sticky="w")
tkgrid(Model_, row=6,column=1, sticky="w")
Tintcpt_<-tklabel(Saisi_, text="intercept",font=PoliceGenerale, state="disabled")
assign("intcpt_", tkentry(Saisi_, width=10, state="disabled"),envir = as.environment(pos))
tkgrid(Tintcpt_, row=6, column=2, sticky="w")
tkgrid(intcpt_, row=6, column=3, sticky="w")
Tstop_=tklabel(Saisi_,text="At the moment an unique stopping rule is proposed: sample size ",
font=PoliceGenerale)
tkgrid(Tstop_, row=7,column=0,columnspan=4, sticky="w")
Tnum_=tklabel(Saisi_,text="Number of patients",font=PoliceGenerale)
N_<-tkentry(Saisi_, width=5)
tkgrid(Tnum_, row=8, column=0, sticky="w")
tkgrid(N_, row=8, column=1, sticky="w")
Tpdist_ = tklabel(Saisi_,text="Prior alpha dist. ",font=PoliceGenerale)
Pdist_ <- tk2spinbox(Saisi_, values = c("Uniform [p1,p2]","Gamma (p1,p2)"),width=15)
tkgrid(Tpdist_ , row=9,column=0, columnspan=2, sticky="w")
tkgrid(Pdist_, row=9,column=1, sticky="w")
Talpha_=tklabel(Saisi_,text="Prior alpha value (DFLT=1)", font=PoliceGenerale)
Tp1_=tklabel(Saisi_,text="p1",font=PoliceGenerale)
Tp2_=tklabel(Saisi_,text="p2",font=PoliceGenerale)
alpha_<-tkentry(Saisi_, width=7)
p1_<-tkentry(Saisi_, width=7);p2_<-tkentry(Saisi_, width=7)
tkgrid(Tp1_, row=10, column=0, sticky="w")
tkgrid(p1_, row=10, column=1, sticky="w")
tkgrid(Tp2_, row=10, column=2, sticky="w")
tkgrid(p2_, row=10, column=3, sticky="w")
tkgrid(Talpha_, row=11, column=0, columnspan=3,sticky="w")
tkgrid(alpha_, row=11, column=2, sticky="w")
Tpoint_=tklabel(Saisi_,text="Pointest in [0, 0.5]",font=PoliceGenerale)
point_<-tkentry(Saisi_, width=10)
tkgrid(Tpoint_, row=12, column=0, columnspan=2, sticky="w")
tkgrid(point_, row=12, column=1, sticky="w")
Titrec_=tklabel(Saisi_,text="Dose skipping constraint",font=PoliceGenerale)
const1_ <- tkradiobutton(Saisi_) ;
const2_ <- tkradiobutton(Saisi_)
rbValue.const_ <- tclVar(1)
tkconfigure(const1_,variable=rbValue.const_,value=1, text="TRUE",font=PoliceGenerale)
tkconfigure(const2_,variable=rbValue.const_,value=0, text="FALSE",font=PoliceGenerale)
tkgrid(Titrec_, row=12, column=2, columnspan=2, sticky="w")
tkgrid(const1_, row=12, column=4, sticky="w")
tkgrid(const2_, row=13,column=4, sticky="w")
Twind_<-tklabel(Saisi_, text="Observation window",font=PoliceGenerale)
Wind_<-tkentry(Saisi_, width=10)
tkgrid(Twind_, row=13,column=0,columnspan=2, sticky="w")
tkgrid(Wind_, row=13,column=1, sticky="w")
Tparr_<-tklabel(Saisi_, text="Mean inter-patient arrival time",font=PoliceGenerale)
Parr_<-tkentry(Saisi_, width=10)
tkgrid(Tparr_, row=14,column=0,columnspan=3, sticky="w")
tkgrid(Parr_, row=14,column=2, sticky="w")
Tacc_<-tklabel(Saisi_, text="Accrual",font=PoliceGenerale)
Acc_<- tk2spinbox(Saisi_, values = c("fixed","poisson"),width=7)
tkgrid(Tacc_, row=15,column=0, sticky="w")
tkgrid(Acc_, row=15,column=1, sticky="w")
Ttox_<-tklabel(Saisi_, text="Time until toxicity occurence",font=PoliceGenerale)
tox_<- tk2spinbox(Saisi_, values = c("uniform","exponential"), width=10)
tkgrid(Ttox_, row=16,column=0,columnspan=3, sticky="w")
tkgrid(tox_, row=16,column=2, sticky="w")
Tseed_<-tklabel(Saisi_, text="Random number generator (seed)",font=PoliceGenerale)
Seed_<-tkentry(Saisi_, width=10)
tkgrid(Tseed_, row=17,column=0,columnspan=2, sticky="w")
tkgrid(Seed_, row=17,column=2, sticky="w")
labage_<-tklabel(Saisi_, text="Name of study ",font=PoliceGenerale)
names.S_<-tkentry(Saisi_, width=20)
tkgrid(labage_, row=18,column=0, sticky="w")
tkgrid(names.S_, row=18,column=1,columnspan=2, sticky="w")
RunSim_=tkbutton(Run_ ,text="Run",width=15,command=.Simulation_,bg="cornflower blue")
tkgrid(RunSim_, row=1)
}
tclArrayVar <- function(Rarray=NULL)
{
if (!is.null(Rarray) && !is.vector(Rarray) && length(dim(Rarray))!=2)
stop("Array must be one-dimensional or two-dimensional.")
n <- .TkRoot$env$TclVarCount <- .TkRoot$env$TclVarCount +1L
name <- paste("::RTcl", n,sep = "")
l <- list(env = new.env(),nrow=0,ncol=0,ndim=0)
assign(name, NULL, envir = l$env)
reg.finalizer(l$env, function(env) tcl("unset", ls(env)))
class(l) <- "tclArrayVar"
if (is.null(Rarray))
{
ndim <- 2
.Tcl(paste("set ",name,"(0,0) \"\"",sep=""))
}
else
{
if (is.vector(Rarray))
{
ndim <- 1
Rarray <- as.data.frame(Rarray)
}
else
ndim <- 2
for (i in (1:nrow(Rarray)))
if (ndim==2)
for (j in (1:ncol(Rarray)))
.Tcl(paste("set ",name,"(",i,",",j,") \"",paste(Rarray[i,j]),"\"",sep=""))
else
.Tcl(paste("set ",name,"(",i,",",1,") \"",paste(Rarray[i,1]),"\"",sep=""))
if (!is.null(rownames(Rarray)))
for (i in (1:nrow(Rarray)))
.Tcl(paste("set ",name,"(",i,",",0,") \"",rownames(Rarray)[i],"\"",sep=""))
else
for (i in (1:nrow(Rarray)))
.Tcl(paste("set ",name,"(",i,",",0,") \"\"",sep=""))
if (!is.null(colnames(Rarray)))
for (j in (1:ncol(Rarray)))
.Tcl(paste("set ",name,"(",0,",",j,") \"",colnames(Rarray)[j],"\"",sep=""))
else
for (j in (1:ncol(Rarray)))
.Tcl(paste("set ",name,"(",0,",",j,") \"\"",sep=""))
l$nrow <- nrow(Rarray)
l$ncol <- ncol(Rarray)
}
l$ndim <- ndim
l
}
print.tclArrayVar <- function(tclArray,height=100,width=100)
{
tt <- tktoplevel()
tclRequire("Tktable")
tclArrayName <- ls(tclArray$env)
table1 <- tkwidget(tt,"table",rows=paste(tclArray$nrow+1),cols=paste(tclArray$ncol+1),colwidth=15,titlerows="1",titlecols="1",
height=paste(height+1),width=paste(width+1))
tkgrid(table1)
tkconfigure(table1,variable=tclArrayName,background="white")
tkconfigure(table1,resizeborders="col")
tkconfigure(table1,multiline="0")
}
save_Qf2=function(){ tkmessageBox(title = "Data storage Infos",
message = "Data are automatically saved after each inclusion", icon = "info", type = "ok")}
save_Qf=function(){ tkmessageBox(title = "Data storage Infos",
message = "Please use the button save study available in interactive TITE-EWOC or simulator to save your data", icon = "info", type = "ok")}
about=function(){ tkmessageBox(title = "Information",
message = "Time-to-Event Escalade With Overdose Control Interface 2017",
icon = "info", type = "ok")}
Open.help=function() {browseURL("https://www.ncbi.nlm.nih.gov/pubmed/21351289", browser=getOption("browser"),
encodeIfNeeded = FALSE) }
frameInit = function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_TEWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_TEWOC, "630x550")
tkwm.geometry(Win_TEWOC, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TEWOC, ilogo)
tktitle(Win_TEWOC) <- "GUI TEWOC"
tkpack.propagate(Win_TEWOC, FALSE)
topMenu <- tk2menu(Win_TEWOC)
tkconfigure(Win_TEWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-EWOC", command=NewTEWOC)
tkadd(newStudyMenu,"command", label="Tite-EWOC simulator", command=SimTEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_TEWOC); frameInit()} )
tkadd(AideMenu,"command", label="Help R (Publi)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TEWOC))
}
frameInitTEWOC = function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_TEWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_TEWOC, "595x600")
tkwm.geometry(Win_TEWOC, "+400+80")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TEWOC, ilogo)
tktitle(Win_TEWOC) <- "GUI TEWOC"
tkpack.propagate(Win_TEWOC, FALSE)
topMenu <- tk2menu(Win_TEWOC)
tkconfigure(Win_TEWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-EWOC", command=NewTEWOC)
tkadd(newStudyMenu,"command", label="Tite-EWOC simulator", command=SimTEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_TEWOC); frameInit()})
tkadd(AideMenu,"command", label="Help R (Publi)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf2)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TEWOC))
assign("net.TEWOC", tk2notebook(Win_TEWOC, tabs = c("Input parameters","Include","Results")),
envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TEWOC , fill = "both", expand = 1)
assign("Resultas", tk2notetab(net.TEWOC , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas, FALSE)
assign("include", tk2notetab(net.TEWOC , "Include"),envir = as.environment(pos))
tkpack.propagate(include, FALSE)
assign("Required", tk2notetab(net.TEWOC , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required, FALSE)
assign("Saisi", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi, FALSE)
assign("Run", tkframe(Required, relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run, FALSE)
assign("m2", tkframe(Required, relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2, row=17, column=0, columnspan=2, rowspan=7)
}
frameInitSIM = function() {
assign("PoliceGenerale", tkfont.create(family="calibri",underline=FALSE, size=12),envir = as.environment(pos))
assign("PoliceTitre", tkfont.create(family="calibri",weight="bold",underline=TRUE, size=10),envir = as.environment(pos))
assign("Win_TEWOC", tktoplevel(background = "light steel blue"),envir = as.environment(pos))
tkwm.geometry(Win_TEWOC, "715x725")
tkwm.geometry(Win_TEWOC, "+400+80")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(Win_TEWOC, ilogo)
tktitle(Win_TEWOC) <- "GUI TEWOC"
tkpack.propagate(Win_TEWOC, FALSE)
topMenu <- tk2menu(Win_TEWOC)
tkconfigure(Win_TEWOC, menu=topMenu)
StudyMenu <- tk2menu(topMenu, tearoff=FALSE)
AideMenu <- tk2menu(topMenu, tearoff=FALSE)
QuitterMenu <- tk2menu(topMenu, tearoff=FALSE)
tkadd(topMenu,"cascade", label="Study", menu=StudyMenu)
tkadd(topMenu,"cascade", label="Help", menu=AideMenu)
tkadd(topMenu,"cascade", label="Exit", menu=QuitterMenu)
newStudyMenu <- tk2menu(StudyMenu, tearoff=FALSE)
tkadd(StudyMenu,"cascade", label="New Study", menu=newStudyMenu)
tkadd(newStudyMenu,"command", label="Interactive Tite-EWOC", command=NewTEWOC)
tkadd(newStudyMenu,"command", label="Tite-EWOC simulator", command=SimTEWOC)
tkadd(StudyMenu,"command", label="Open Study",command=loads)
tkadd(StudyMenu,"command", label="Close Study",command=function(){ tkdestroy(Win_TEWOC); frameInit()})
tkadd(AideMenu,"command", label="Help R (Publi)", command=Open.help)
tkadd(AideMenu,"command", label="About", command=about)
tkadd(QuitterMenu,"command", label="Save_Quit", command=save_Qf)
tkadd(QuitterMenu,"command", label="No_Save_Quit", command=function() tkdestroy(Win_TEWOC))
assign("net.TEWOC_", tk2notebook(Win_TEWOC, tabs = c("Input parameters","Results")),envir = as.environment(pos))
tcl("ttk::style", "configure", "TNotebook.Tab",font=PoliceGenerale)
tcl("ttk::style", "map", "TNotebook.Tab", background=c("active", "cornflower blue"))
tkpack(net.TEWOC_ , fill = "both", expand = 1)
assign("Resultas_", tk2notetab(net.TEWOC_ , "Results"),envir = as.environment(pos))
tkpack.propagate(Resultas_, FALSE)
assign("Required_", tk2notetab(net.TEWOC_ , "Input parameters"),envir = as.environment(pos))
tkpack.propagate(Required_, FALSE)
assign("Saisi_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Saisi_, FALSE)
assign("Run_", tkframe(Required_,relief="groove",borderwidth=3),envir = as.environment(pos))
tkpack.propagate(Run_, FALSE)
assign("m2_", tkframe(Required_,relief="groove",borderwidth=2),envir = as.environment(pos))
tkgrid(m2_, row=17, column=0, columnspan=2, rowspan=7)
}
frameInit()
}
.ewocht<- function (a, x, y, w, p1, p2,law)
{
v=switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((((tanh(x[i])+1)/2)^a)^y[i]) * ((1 - w[i]*(((tanh(x[i])+1)/2)^a))^(1-y[i]))
}
return(v)
}
.ewochte<-function (a, x, y, w, p1, p2, law)
{
v=a*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((((tanh(x[i])+1)/2)^a)^y[i]) * ((1 - w[i]*(((tanh(x[i])+1)/2)^a))^(1-y[i]))
}
return(v)
}
.ewochtv<-function (a, x, y, w, p1, p2, law)
{
v=(a^2)*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((((tanh(x[i])+1)/2)^a)^y[i]) * ((1 - w[i]*(((tanh(x[i])+1)/2)^a))^(1-y[i]))
}
return(v)
}
.ewoclgt <-function (a, x, y, w, p1, p2, cst, law)
{
v=switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * (plogis(cst+a*x[i])^y[i]) *
((1-w[i]*plogis(cst+a*x[i]))^(1-y[i]))
}
return(v)
}
.ewoclgte <-function (a, x, y, w, p1, p2, cst, law)
{
v=a*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * (plogis(cst+a*x[i])^y[i]) *
((1-w[i]*plogis(cst+a*x[i]))^(1-y[i]))
}
return(v)
}
.ewoclgtv <-function (a, x, y, w, p1, p2, cst, law)
{
v=(a^2)*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * (plogis(cst+a*x[i])^y[i]) *
((1-w[i]*plogis(cst+a*x[i]))^(1-y[i]))
}
return(v)
}
.ewocpw <-function (a, x, y, w, p1, p2, law)
{
v=switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((x[i]^a)^y[i]) * ((1-w[i]*(x[i]^a))^(1-y[i]))
}
return(v)
}
.ewocpwe <-function (a, x, y, w, p1, p2, law)
{
v=a*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((x[i]^a)^y[i]) * ((1-w[i]*(x[i]^a))^(1-y[i]))
}
return(v)
}
.ewocpwv <-function (a, x, y, w, p1, p2, law)
{
v=(a^2)*switch(law,gamma=dgamma(a, shape = p1, scale = p2),unif=dunif(a,p1,p2))
for (i in 1:length(x)) {
v = v * ((x[i]^a)^y[i]) * ((1-w[i]*(x[i]^a))^(1-y[i]))
}
return(v)
}
.HTGamma<-function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow((exp(d[i])/(exp(d[i]) + exp(-d[i]))), alpha)
}
alpha ~ dgamma(p1, 1/p2)
}
.PowerGamma<-function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow(d[i], alpha)
}
alpha ~ dgamma(p1, 1/p2)
}
.LogisticGamma<-function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*ilogit(intcpt + alpha * d[i])
}
alpha ~ dgamma(p1, 1/p2)
}
.HTUnif <- function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow((exp(d[i])/(exp(d[i]) + exp(-d[i]))), alpha)
}
alpha ~ dunif(p1, p2)
}
.LogisticUnif <- function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*ilogit(intcpt + alpha * d[i])
}
alpha ~ dunif(p1, p2)
}
.PowerUnif <- function ()
{
for (i in 1:N1) {
s[i] ~ dbin(p[i], n[i])
p[i] <- w[i]*pow(d[i], alpha)
}
alpha ~ dunif(p1, p2)
}
.titeewoc <- function(prior, target, dose=NULL, tox=NULL, level, n = length(level), weights = NULL, followup = NULL,
obswin = NULL, method = "exact", model = "ht", constrain = TRUE, pointest="plugin", p.dist="unif",
p1 = ifelse(p.dist == "gamma", 2, 0), p2=ifelse(p.dist == "gamma", 0.7, 5), alphap=1,
intcpt = 3, seed=NULL, burnin.itr = 2000, production.itr = 2000)
{
if (is.null(weights)) {
if (!(is.null(followup) | is.null(obswin))) {
weights <- followup/obswin
} else {
stop("Cannot define weigths, check followup and obswin")
}
} else { weigths <- pmin(weights, 1)}
if (any(weights > 1) | any(weights < 0))
stop(" Weights have to be between 0 and 1!")
if (!is.null(dose)) {
if (!(length(dose) == length(prior)))
stop(" Prior and dose must be of same lengths")
}
if (!(length(tox) == length(level) & length(tox) == length(weights)))
stop(" tox, level, and weights must be of same lengths!")
if (missing(prior))
stop(" Prior proabilities are missing")
if (any(prior > 1) | any(prior < 0))
stop(" Prior probabilities have to be between 0 and 1!")
if ((target > 1) | (target < 0))
stop(" Target has to be between 0 and 1!")
if ((!model %in% c("ht", "logit1", "power")))
stop("model must be one of 'ht', 'logit1', 'power'")
if ((!p.dist %in% c("unif", "gamma")))
stop("Prior distribution must be one of 'unif', 'gamma'")
if ((p.dist == "unif")& (p2<=p1))
stop("invalid parameters p1 and p2")
if ((!method %in% c("exact", "rjags")))
stop ("unknown estimation method")
if (!((pointest=="plugin")|((pointest <= 0.5)&(pointest > 0))))
stop ("Pointest must be equal to 'plugin' or between ]0,0.5]")
if (!(pointest=="plugin")&(method=="exact"))
warning("Only pointest equals to plugin is available for exact method")
if (!is.null(seed))
set.seed(seed)
if (missing(level))
stop(" Level is missing")
weights[tox == 1] <- 1
y1p <- tox
w1p <- weights
k <- length(prior)
nb.pat.level <- rep(0,k)
nb.tox.level <- rep(0,k)
weights.level<- rep(0,k)
for (i in 1:k){
nb.pat.level[i]<-table(factor(level, levels = 1:k))[[i]]
nb.tox.level[i]<-xtabs(tox~factor(level, levels = 1:k))[[i]]
weights.level[i]<-xtabs(w1p~factor(level, levels = 1:k))[[i]]}
inzero=which(nb.pat.level!=0)
weights.level[inzero] <- weights.level[inzero]/nb.pat.level[inzero]
if (method == "exact") {
if (model == "ht") {
dosescaled <- atanh(2*prior^(1/alphap)-1)
x1p <- dosescaled[level]
f.model <-function(dose, alpha,cst) {
((tanh(dose) + 1)/2)^alpha}
cst.den <- integrate(.ewocht, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]
est <- integrate(.ewochte, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den
cdf <- function(aU){ integrate(.ewocht, 0, aU, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den}
ptox <- f.model(dosescaled,est,1)
mtd. <- atanh(2*target^(1/est)-1)
}
if (model == "logit1") {
dosescaled <- (qlogis(prior) - intcpt)/alphap
x1p <- dosescaled[level]
f.model <- function(dose, alpha,cst) {plogis(cst+alpha*dose)}
cst.den <- integrate(.ewoclgt, 0, Inf, x1p, y1p, w1p, p1, p2,
intcpt, p.dist, abs.tol = 0)[[1]]
est <- integrate(.ewoclgte, 0, Inf, x1p, y1p, w1p, p1, p2,
intcpt, p.dist, abs.tol = 0)[[1]]/cst.den
cdf <- function(aU){ integrate(.ewoclgt, 0, aU, x1p, y1p, w1p, p1, p2,
intcpt, p.dist, abs.tol = 0)[[1]]/cst.den}
ptox <- f.model(dosescaled,est,intcpt)
mtd. <- (log(target/(1 - target)) - intcpt)/est
}
if (model == "power") {
dosescaled <- prior^(1/alphap)
x1p <- dosescaled[level]
f.model <- function(dose, alpha, cst) {dose^alpha}
cst.den <- integrate(.ewocpw, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]
est <- integrate(.ewocpwe, 0, Inf, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den
cdf <- function(aU){integrate(.ewocpw, 0, aU, x1p, y1p, w1p, p1, p2, p.dist,
abs.tol = 0)[[1]]/cst.den}
ptox <- f.model(dosescaled,est,1)
mtd. <- target^(1/est)
}
fn <- function(aU_, q) {abs(cdf(aU_) - q)}
alpha.quantiles <- sapply(c(0.025, 0.25, 0.5, 0.75, 0.975),
function(q) {
max.x <- seq(0, 10*est, length = 100)[which.min(sapply(seq(0,
10*est, length = 100), function(i) {
fn(i, q)
}))]
if(max.x==0){max.x <-0.001}
optimize(fn, c(0, max.x), q = q, tol = .Machine$double.eps^0.5)$minimum
})
quantiles <- sapply(dosescaled, function(d) {
f.model(d, sort(alpha.quantiles, TRUE),intcpt)
})
alpha.quantiles<- matrix(alpha.quantiles,nrow=1,ncol=5)
rownames(quantiles) <- colnames(alpha.quantiles) <-
c("2.5%", "25%", "50%", "75%", "97.5%")
current <- level[length(level)]
if (all(ptox <= target)) {
dose.rec <- k
} else if (all(ptox >= target)) {
dose.rec <- 1
} else {
dose.rec <- if (!constrain) {
which.min(abs(ptox - target))
}else {
which.min(abs(ptox[1:min(current + 1, k)] - target))
}
}
results <- list(dose.rec = dose.rec, alpha.est = est, alpha.quantiles=alpha.quantiles,
post.ptox=ptox,quantiles.ptox = quantiles, prior=prior, target=target, model=model,
method=method, prior.alpha=list(dist=p.dist,p1=p1,p2=p2), sdose=dosescaled,
constrain=constrain, pointest=pointest, nb.pat.level=nb.pat.level,
nb.tox.level=nb.tox.level, weights.m.level=weights.level)
}else{
if (model == "ht"){
model.file <- switch(p.dist,gamma=.HTGamma, unif=.HTUnif)
f.dose<- function(alpha,ptox, cst) atanh(2*ptox^(1/alpha)-1)
f.model <- function(dose, alpha,cst) {
((tanh(dose) + 1)/2)^alpha}
dosescaled <- f.dose(alphap, prior, intcpt)
} else if (model == "logit1") {
model.file <- switch(p.dist,gamma=.LogisticGamma, unif=.LogisticUnif)
f.dose<- function(alpha,ptox, cst)(qlogis(ptox) - cst)/alpha
f.model <- function(dose, alpha,cst) {plogis(cst+alpha*dose)}
dosescaled <- f.dose(alphap,prior,intcpt)
} else {
model.file <- switch(p.dist,gamma=.PowerGamma, unif=.PowerUnif)
f.dose <- function(alpha,ptox, cst) ptox^(1/alpha)
f.model <- function(dose, alpha, cst) {dose^alpha}
dosescaled <- f.dose(alphap,prior,intcpt)
}
if (model == "logit1"){
mydata <- list(N1 = k, s = nb.tox.level, w=weights.level, d = dosescaled, p1 = p1,
p2 = p2, intcpt=intcpt, n=nb.pat.level)
}else {mydata <- list(N1 = k, s = nb.tox.level, w=weights.level, d = dosescaled,
p1 = p1, p2 = p2, n=nb.pat.level) }
path.model <- file.path(tempdir(), "model.file.txt")
R2WinBUGS::write.model(model.file, path.model)
r.init <- switch(p.dist,gamma=rgamma(1,shape=p1,scale=p2),unif=runif(1, p1, p2))
inits.list <- list(list(alpha = 1, .RNG.seed = sample(1:1e+06, size = 1),
.RNG.name = "base::Wichmann-Hill"),
list(alpha = r.init, .RNG.seed = sample(1:1e+06, size = 1), .RNG.name = "base::Wichmann-Hill"))
jagsobj <- rjags::jags.model(path.model, data = mydata, n.chains = 2,
quiet = TRUE, inits = inits.list)
update(jagsobj, n.iter = burnin.itr, progress.bar = "none")
j.samples <- rjags::jags.samples(jagsobj, "alpha", n.iter = production.itr/2,
progress.bar = "none")
alpha.samples <- c(j.samples$alpha)
alpha.quantiles<-apply(as.matrix(alpha.samples),2,quantile, c(0.025, 0.25, 0.5,
0.75, 0.975))
samples.ptox <- sapply(dosescaled, function(d) {
f.model(d, alpha.samples, intcpt)})
quantiles <- apply(samples.ptox, 2, quantile, c(0.025, 0.25,
0.5, 0.75, 0.975))
mean.alpha <- apply(as.matrix(alpha.samples), 2, mean)
if (pointest=="plugin") {
ptox <- sapply(dosescaled, function(d) {
f.model(d, mean.alpha,intcpt)
})
} else { ptox <- NA}
if (pointest!= "plugin") {
mtd <- f.dose(alpha=alpha.samples,ptox = target,cst=intcpt)
target.mtd <- quantile(mtd, pointest)
}
current <- level[length(level)]
dose.rec <- if (pointest == "plugin") {
if (!constrain) {
which.min(abs(ptox - target))
}else {
which.min(abs(ptox[1:min(current + 1, k)] - target))
}
} else { if (!constrain) {
which.min(abs(dosescaled - target.mtd))
}else {
which.min(abs(dosescaled[1:min(current + 1, k)] - target.mtd))
}
}
results<-list(dose.rec = dose.rec, alpha.mean = mean.alpha, alpha.quantiles=alpha.quantiles,
post.ptox=ptox, quantiles.ptox = quantiles, prior=prior, target=target, model=model, mtd.est=target.mtd,
method=method, prior.alpha=list(dist=p.dist,p1=p1,p2=p2), sdose=dosescaled, constrain=constrain,
pointest=pointest, nb.pat.level=nb.pat.level, nb.tox.level=nb.tox.level,
weights.m.level=weights.level)
}
class(results) <- "Tite-Ewoc"
return (results)
}
.titeewocsim <- function(nsim, true, prior, target, dose=NULL, accrual = "fixed", obswin = NULL, tparr = obswin,
start = 1, samplesize, method = "exact", pointest=0.25, model = "ht", toxocc="unif",
p.dist="unif", alphap = 1, p1 = ifelse(p.dist == "gamma", 2, 0),
p2=ifelse(p.dist == "gamma", 0.7, 1), intcpt = 3, rateexp=1/obswin,
constrain = TRUE, count =FALSE, seed=NULL, burnin.itr = 2000, production.itr = 2000)
{
if (missing(nsim))
stop(" Number of simulations is missing")
if (is.null(obswin))
stop("Observation window must be defined")
if (missing(prior))
stop(" Prior proabilities are missing")
if (any(prior > 1) | any(prior < 0))
stop(" Prior probabilities have to be between 0 and 1!")
if (missing(true))
stop(" True proabilities are missing")
if (any(true > 1) | any(true < 0))
stop(" True probabilities have to be between 0 and 1!")
if ((target > 1) | (target < 0))
stop(" Target has to be between 0 and 1!")
if ((!model %in% c("ht", "logit1", "power", "logit2")))
stop("model must be one of 'ht', 'logit1', 'power' or 'logit2'")
if ((!method %in% c("exact", "rjags")))
stop ("unknown estimation method")
if ((!accrual %in% c("fixed", "poisson")))
stop ("unknown patient accrual scheme")
if ((!toxocc %in% c("unif", "exp")))
stop ("unknown distribution for time-to-toxicity")
if (!((pointest=="plugin")|((pointest <= 0.5)&(pointest > 0))))
stop ("Pointest must be equal to 'plugin' or between ]0,0.5]")
if (!(pointest=="plugin")&(method=="exact"))
warning("Only pointest equals to plugin is available for exact method")
if (!is.null(seed))
set.seed(seed)
if (missing(samplesize))
stop(" Sample size is missing")
if (!is.null(dose)) {
if (!(length(dose) == length(prior)))
stop("Prior and dose must be of same lengths")
if (start > (length(prior)))
start <- min(which(start == dose))
}
if (!(length(prior) == length(true)))
stop("Prior and true probabilities must be of same lengths")
if (length(start) > 1)
stop("Start must be a single value")
k <- length(prior)
dose.rec <- DURATION <- rep(NA, nsim)
alphaDist <- rep(NA, nsim)
nb.pat.level <- matrix(NA,nrow=nsim,ncol=k)
nb.tox.level <- matrix(NA,nrow=nsim,ncol=k)
dose.rec.level <- numeric(k)
sim <- 1
for (sim in 1:nsim) {
if (count) {
cat("simulation number:", sim, "\n")
}
if (accrual == "fixed") {
next.arrival <- rep(tparr,samplesize)
}else if (accrual == "poisson") {
next.arrival <- rpois(samplesize, tparr)
}
level <- rep(NA,samplesize)
level[1] <- start
w <- y <- followuppat <- numeric(samplesize)
if (toxocc == "unif")
TItox <- round(runif(samplesize, 0, obswin))
if (toxocc == "exp")
TItox <- pmin(round(rexp(samplesize, rate=rateexp)),obswin)
ttox <- t(matrix(rbinom(samplesize*k, 1, true),k,samplesize))
for (i in 1:samplesize)
{
y[i] <- ttox[i,level[i]]
if (y[i]==1) {
followuppat[i] <- TItox[i]
w[i] <- 1}
for (j in 1:i) {
if (y[j]==0){followuppat[j] <- min(followuppat[j]+ next.arrival[i],obswin)
w[j]<-followuppat[j]/obswin }
}
w <- pmin(w,1)
obj<-.titeewoc(prior=prior,target=target, dose=dose, obswin=obswin, tox=y[1:i],level=level[1:i], n = i,
weights = w[1:i], method = method, model = model, constrain = constrain, pointest=pointest,
p.dist=p.dist, p1 = p1, p2 = p2, intcpt = intcpt, alphap=alphap,
burnin.itr = burnin.itr, production.itr = production.itr)
if (i < samplesize)
level[i+1]<-obj$dose.rec
}
level.pat<-table(factor(level, levels = 1:k))
level.tox<-xtabs(y~factor(level, levels = 1:k))
for (l in 1:k){
nb.pat.level[sim,l]<-level.pat[[l]]
nb.tox.level[sim,l]<-level.tox[[l]]
}
dose.rec[sim] <- obj$dose.rec
DURATION[sim] <- sum(next.arrival[1:(samplesize-1)])+followuppat[samplesize]
if (method == "exact") {
alphaDist[sim] <-obj$alpha.est
} else {
if (model == "logit2"){
alphaDist[sim,] <-obj$alpha.mean}
else { alphaDist[sim] <-obj$alpha.mean }
}
}
for (l in 1:k){
dose.rec.level[l]<-table(factor(dose.rec, levels = 1:k))[[l]]}
dose.rec.level<-dose.rec.level/nsim*100
sim.results<-list(pct.dose.rec = dose.rec.level, prior=prior, true=true,
target=target, pat.level=colMeans(nb.pat.level), nb.tox.level=colSums(nb.tox.level),
duration=DURATION, alphaDist = alphaDist, method=method, samplesize=samplesize,
nsim=nsim, start=start, model=model)
class(sim.results) <- "Tite-Ewoc.Sim"
return (sim.results)
}
.print.titeewoc <- function(x)
{
cat(" Estimation method: ", x$method, "\n")
model.txt <- switch(x$model, ht = "Hyperbolic Tangent", logit1 = "1-parameter logistic",
power = "1-parameter power", logit2 = "Two-parameter logistic")
cat("\n Model: ", model.txt, "\n")
if (!(x$model == "logit2")) {
cat("\n Prior.alpha:", x$prior.alpha[1],"", "Param1:", x$prior.alpha[2],
"Param2:", x$prior.alpha[3], "\n")
}
dose.txt <- x$sdose
cat("\n Standardised doses : \n")
print(dose.txt)
if (x$constrain) {
cat("\n Modified (constrained) CRM used, starting dose level: ", "\n")
} else {
cat("\n Unmodified (unconstrained) CRM used \n")
}
if (x$pointest == "plugin") {
cat("\n Plug-in estimate of probability of toxicity used to select next dose \n")
} else {
cat("\n", 100 * x$pointest, "percentile of (standardised) MTD distribution used to select next dose",
"\n", 100 * x$pointest, "percentile is:", x$mtd.est,"\n")
}
tab <- rbind(x$nb.pat.level, x$nb.tox.level)
rownames(tab) <- c("n_Patient", "n_Tox")
colnames(tab) <- c(1:length(x$nb.tox.level))
colnames(tab) <- paste0("dose_",colnames(tab))
cat("\n Toxicities observed: \n")
print(tab)
tab2 <- signif(x$quantiles.ptox,3)
colnames(tab2) <- colnames(tab)
cat("\n Quantiles of posterior estimates of toxicity:: \n")
print(tab2)
cat("\n Next recommended dose level: ", x$dose.rec, "\n")
}
.print.titeewoc.sim <- function(x)
{
cat("Operating characteristics based on", x$nsim , "simulations: ", "\n")
cat("Starting dose level:", x$start , "\n")
cat("Sample size:", x$samplesize, "\n")
model.txt <- switch(x$model, ht = "Hyperbolic Tangent", logit1 = "1-parameter logistic",
power = "1-parameter power", logit2 = "Two-parameter logistic")
cat("\n Model: ", model.txt, "\n")
cat("\n Average study duration (mean [min,max]): ",
mean(x$duration),"[",min(x$duration),",", max(x$duration),"]", "\n")
tab <- signif(rbind(x$pct.dose.rec,x$pat.level),2)
rownames(tab) <- c("Recommended dose pourcentage", "Proportion of patients treated")
colnames(tab) <- c(1:length(x$pat.level))
colnames(tab) <- paste0("dose_",colnames(tab))
print(tab)
}
.plot.titeewoc <- function(x)
{
if (class(x)=="Tite-Ewoc") {
probs=t(x$quantiles.ptox)
plot.data = data.frame(
y2.5 = probs[,1],
y25 = probs[,2],
y50 = probs[,3],
y75 = probs[,4],
y97.5 = probs[,5],
dose.level=c(1:dim(x$quantiles.ptox)[2]),
target=x$target)
plot.data$dose.level=factor(plot.data$dose.level)
p <-ggplot2::ggplot(plot.data, aes(x=dose.level)) +
ggplot2::geom_boxplot(
aes(ymin = y2.5, lower = y25, middle = y50, upper = y75, ymax = y97.5,
color=dose.level),
stat = "identity"
) + ggplot2::ggtitle("Posterior p(DLT) quantiles: 2.5%, 25%, 50%, 75%, 97.5%") +
ggplot2::geom_hline(aes(yintercept = target),data = plot.data, col = 4, linetype = 2)
return(p)
} else {stop (" Plot defined only for Tite-Ewoc object") }
}
GUIP1 <- function()
{
e <- new.env()
welcome = function()
{
PoliceGenerale <- tkfont.create(family="calibri",underline=FALSE, size=14)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=20)
e$Win_GUIP1=tktoplevel(background = "light steel blue")
tkwm.geometry(e$Win_GUIP1, "765x450")
tkwm.geometry(e$Win_GUIP1, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(e$Win_GUIP1, ilogo)
tktitle(e$Win_GUIP1) <- "GUIP1"
tkpack.propagate(e$Win_GUIP1, FALSE)
e$wlc <- tkframe(e$Win_GUIP1,relief="groove",borderwidth=3)
tkpack.propagate(e$wlc, FALSE)
tkgrid(e$wlc, row=0, column=0, sticky="se")
tkgrid(tklabel(e$wlc, text="Welcome to GUIP1",font=PoliceTitre), row=0,columnspan=1, column=2 )
tkgrid(tklabel(e$wlc, text=" "), row=1, column=0)
tkgrid(tklabel(e$wlc, text="To start select one of the following model-guided adaptive designs",font=PoliceGenerale),
row=2, column=1,columnspan=3)
tkgrid(tklabel(e$wlc, text="
"), row=3, column=0)
CRMBbut=tkbutton(e$wlc, text="Bayesian-CRM", width=20, command=function(){dis.welcome();.CRMB(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMBbut, row=4, column=1)
CRMLbut=tkbutton(e$wlc,text="CRM-Likelihood",width=20,command=function(){dis.welcome();.CRML(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMLbut, row=4, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=5, column=0)
TITECRMbut=tkbutton(e$wlc,text="TITE-CRM", width=20, command=function(){dis.welcome();.TITECRM(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITECRMbut, row=6, column=2)
tkgrid(tklabel(e$wlc, text="
"), row=7, column=0)
EWOCbut=tkbutton(e$wlc,text="EWOC", width=20, command=function(){dis.welcome();.EWOC(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(EWOCbut, row=8, column=1)
TITEEWOCbut=tkbutton(e$wlc,text="TITE-EWOC", width=20, command=function(){dis.welcome();.TEWOC(e=e)}, bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITEEWOCbut, row=8, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=9, column=4)
}
dis.welcome = function()
{
tkdestroy(e$Win_GUIP1)
PoliceGenerale<- tkfont.create(family="calibri",underline=FALSE, size=14)
PoliceTitre <- tkfont.create(family="calibri",weight="bold",underline=TRUE, size=20)
e$Win_GUIP1=tktoplevel(background = "light steel blue")
tkwm.geometry(e$Win_GUIP1, "765x459")
tkwm.geometry(e$Win_GUIP1, "+400+180")
ilogo <- tk2ico.load(file.path(Sys.getenv("R_HOME"), "bin", "R.exe"), res = "R")
tk2ico.set(e$Win_GUIP1, ilogo)
tktitle(e$Win_GUIP1) <- "GUIP1"
tkpack.propagate(e$Win_GUIP1, FALSE)
e$wlc <- tkframe(e$Win_GUIP1,relief="groove",borderwidth=3)
tkpack.propagate(e$wlc, FALSE)
tkgrid(e$wlc, row=0, column=0, sticky="se")
tkgrid(tklabel(e$wlc, text="Welcome to GUIP1",font=PoliceTitre), row=0,columnspan=1, column=2 )
tkgrid(tklabel(e$wlc, text=" "), row=1, column=0)
tkgrid(tklabel(e$wlc, text="To launch a new model-guided adaptive design, please close ongoing
study and press refresh button",font=PoliceGenerale),
row=2, column=1,columnspan=3)
tkgrid(tklabel(e$wlc, text="
"), row=3, column=0)
CRMBbut=tkbutton(e$wlc, text="Bayesian-CRM", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMBbut, row=4, column=1)
CRMLbut=tkbutton(e$wlc,text="CRM-Likelihood",width=20,state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(CRMLbut, row=4, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=5, column=0)
TITECRMbut=tkbutton(e$wlc,text="TITE-CRM", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITECRMbut, row=6, column=2)
tkgrid(tklabel(e$wlc, text="
"), row=7, column=0)
EWOCbut=tkbutton(e$wlc,text="EWOC", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(EWOCbut, row=8, column=1)
TITEEWOCbut=tkbutton(e$wlc,text="TITE-EWOC", width=20, state="disabled", bg="cornflower blue", font=PoliceGenerale)
tkgrid(TITEEWOCbut, row=8, column=3)
tkgrid(tklabel(e$wlc, text="
"), row=9, column=4)
TITECRMbut=tkbutton(e$wlc,text="Refresh", width=11, command=function(){tkdestroy(e$Win_GUIP1);GUIP1()}, bg="yellow", font=PoliceGenerale)
tkgrid(TITECRMbut, row=10, column=2)
}
welcome()
}
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