examples/design-method-simulateDualResponsesSamplesDesign.R

In 0liver0815/onc-crmpack-test: Object-Oriented Implementation of CRM Designs

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##Simulate dose-escalation procedure based on DLE and efficacy responses where DLE
## and efficacy samples are used
data <- DataDual(doseGrid=seq(25,300,25),placebo=FALSE)
##First for the DLE model
##The DLE model must be of 'ModelTox' (e.g 'LogisticIndepBeta') class
DLEmodel <- LogisticIndepBeta(binDLE=c(1.05,1.8),
                              DLEweights=c(3,3),
                              DLEdose=c(25,300),
                              data=data)

##The efficacy model of 'ModelEff' (e.g 'Effloglog') class
Effmodel<-Effloglog(Eff=c(1.223,2.513),Effdose=c(25,300),
                    nu=c(a=1,b=0.025),data=data,c=0)


##The escalation rule using the 'NextBestMaxGainSamples' class
mynextbest<-NextBestMaxGainSamples(DLEDuringTrialtarget=0.35,
                                   DLEEndOfTrialtarget=0.3,
                                   TDderive=function(TDsamples){
                                     quantile(TDsamples,prob=0.3)},
                                   Gstarderive=function(Gstarsamples){
                                     quantile(Gstarsamples,prob=0.5)})


##The increments (see Increments class examples)
## 200% allowable increase for dose below 300 and 200% increase for dose above 300
myIncrements<-IncrementsRelative(intervals=c(25,300),
                                 increments=c(2,2))
##cohort size of 3
mySize<-CohortSizeConst(size=3)
##Stop only when 10 subjects are treated (only for illustration such a low
##sample size)
myStopping <- StoppingMinPatients(nPatients=10)
##Now specified the design with all the above information and starting with
##a dose of 25


##Specified the design
design <- DualResponsesSamplesDesign(nextBest=mynextbest,
                                     cohortSize=mySize,
                                     startingDose=25,
                                     model=DLEmodel,
                                     Effmodel=Effmodel,
                                     data=data,
                                     stopping=myStopping,
                                     increments=myIncrements)
##specified the true DLE and efficacy curve
myTruthDLE <- probFunction(DLEmodel, phi1 = -53.66584, phi2 = 10.50499)

myTruthEff<- function(dose)
{Effmodel@ExpEff(dose,theta1=-4.818429,theta2=3.653058)
}
##The true gain curve can also be seen
myTruthGain <- function(dose)
{return((myTruthEff(dose))/(1+(myTruthDLE(dose)/(1-myTruthDLE(dose)))))}

##simulate the trial for 10 times involving samples
##for illustration purpose we use 10 burn-ins to generate 50 samples
options<-McmcOptions(burnin=10,step=1,samples=50)
##For illustration purpose only 1 simulations are produced (nsim=1).
mySim<-simulate(design,
                 args=NULL,
                 trueDLE=myTruthDLE,
                 trueEff=myTruthEff,
                 trueNu=1/0.025,
                 nsim=1,
                 mcmcOptions=options,
                 seed=819,
                 parallel=FALSE)



##Simulate dose-escalation procedure based on DLE and efficacy responses where DLE
## and efficacy samples are used
## when the efficacy model is of 'EffFlexi' class
Effmodel<- EffFlexi(Eff=c(1.223, 2.513),Effdose=c(25,300),
                    sigma2=c(a=0.1,b=0.1),sigma2betaW=c(a=20,b=50),smooth="RW2",data=data)


##Specified the design
design <- DualResponsesSamplesDesign(nextBest=mynextbest,
                                     cohortSize=mySize,
                                     startingDose=25,
                                     model=DLEmodel,
                                     Effmodel=Effmodel,
                                     data=data,
                                     stopping=myStopping,
                                     increments=myIncrements)
##specified the true DLE curve and the true expected efficacy values at all dose levels
myTruthDLE <- probFunction(DLEmodel, phi1 = -53.66584, phi2 = 10.50499)

myTruthEff<- c(-0.5478867, 0.1645417,  0.5248031,  0.7604467,
               0.9333009  ,1.0687031,  1.1793942 , 1.2726408 ,
               1.3529598 , 1.4233411 , 1.4858613 , 1.5420182)
##The true gain curve can also be seen
d1 <- data@doseGrid
myTruthGain <- (myTruthEff)/(1+(myTruthDLE(d1)/(1-myTruthDLE(d1))))


mySim<-simulate(object=design,
                args=NULL,
                trueDLE=myTruthDLE,
                trueEff=myTruthEff,
                trueSigma2=0.025,
                trueSigma2betaW=1,
                mcmcOptions=options,
                nsim=1,
                seed=819,
                parallel=FALSE)

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