Nothing
R/17_nlme-BOV-ETA-SLOPE-EC50-EMAX-v22.R
In cardioModel: Cardiovascular Safety Exposure-Response Modeling in Early-Phase Clinical Studies
###################################################################################
##############ETAs IN BASELINE & SLOPE/EC50/EMAX BOV for PERIOD######################
###################################################################################
myModeling17 <- function(myData, AIC.k, delay.confidence){
#library(nlme)
i.int <- mean(myData$RESPONSE, na.rm = TRUE)
i.amp <- sd(myData$RESPONSE, na.rm = TRUE)
i.tpeak1 <- 0
i.tpeak2 <- 0
mask.na.for.fNTAFD <-
!(myData[, "EXPOSURE"] %in% NA) &
!(myData[, "RESPONSE"] %in% NA) & !(myData[, "fNTAFD"] %in% NA)
i.fNTAFD <- rep(i.int,length(unique(myData$fNTAFD[mask.na.for.fNTAFD])))
i.slo <- 0
i.emax <- i.amp
i.ec50 <- log(mean(myData$EXPOSURE, na.rm = TRUE))
i.hill <- log(1)
dfEmpty <- data.frame(MODEL=NA, AIC=NA, SLOPE=NA, VAR.SLOPE=NA, EMAX=NA, VAR.EMAX=NA,
EC50=NA, VAR.EC50=NA, COV.EMAX.EC50=NA, HILL=NA, VAR.HILL=NA,
COV.EMAX.HILL=NA, COV.EC50.HILL=NA, DRUG.EFFECT.DELAY=NA,
ERROR.MESSAGE=NA)
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- data.frame()
saved.models = list()
#################Estimated E0############################################
##Mod02-E0+Emax
tmp <- dfEmpty
tmp$MODEL <- "91, model = e0 + emax, bsv = e0 +ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Int+Emax+EC50~1,
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(Int=i.int, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod03-E0+SigEma
tmp <- dfEmpty
tmp$MODEL <- "92, model = e0 + sigmoidal emax, bsv = e0 + ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Int+Emax+EC50+Hill~1,
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(Int=i.int, Emax=i.emax, EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Estimated E0+fNTAFD##########################################
##Mod05-E0/fNTAFD+Emax
tmp <- dfEmpty
tmp$MODEL <- "93, model = e0~fNTAFD + emax, bsv = e0 + ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=list(Int~fNTAFD-1, Emax+EC50~1),
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(i.fNTAFD, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod06-E0/fNTAFD+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "94, model = e0~fNTAFD + sigmoidal emax, bsv = e0 + ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=list(Int~fNTAFD-1, Emax+EC50+Hill~1),
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(i.fNTAFD, Emax=i.emax, EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Cosine Period 24h############################################
##Mod08-Cos24+Emax
tmp <- dfEmpty
tmp$MODEL <- "95, model = cosine 24 h period + emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine24.fun(Mean, Amp1, Tpeak1, TOD=TOD)+
.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Emax+EC50~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Emax=i.emax,
EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod09-Cos24+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "96, model = cosine 24 h period + sigmoidal emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine24.fun(Mean, Amp1, Tpeak1, TOD=TOD)+
.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Emax+EC50+Hill~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Emax=i.emax,
EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Cosine Period 12h############################################
##Mod11-Cos12+Emax
tmp <- dfEmpty
tmp$MODEL <- "97, model = cosine 12 h period + emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine12.fun(Mean, Amp2, Tpeak2, TOD=TOD)+
.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp2+Tpeak2+Emax+EC50~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp2=i.amp, Tpeak2=i.tpeak2, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod12-Cos12+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "98, model = cosine 12 h period + sigmoidal emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine12.fun(Mean, Amp2, Tpeak2, TOD=TOD)+
.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp2+Tpeak2+Emax+EC50+Hill~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp2=i.amp, Tpeak2=i.tpeak2, Emax=i.emax,
EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Double Cosine############################################
##Mod14-Dcos+Emax
tmp <- dfEmpty
tmp$MODEL <- "99, model = double cosine + emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.dcosine.fun(Mean, Amp1, Tpeak1, Amp2, Tpeak2, TOD=TOD)+
.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Amp2+Tpeak2+Emax+EC50~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Amp2=i.amp,
Tpeak2=i.tpeak2, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod15-Dcos+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "100, model = double cosine + sigmoidal emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.dcosine.fun(Mean, Amp1, Tpeak1, Amp2, Tpeak2, TOD=TOD)+
.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Amp2+Tpeak2+Emax+EC50+Hill~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Amp2=i.amp,
Tpeak2=i.tpeak2, Emax=i.emax, EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#Replace fake error by none
mask.fake.error <- grep("try", results.nlme.ETA.BL.SLO.EC50.EMAX.BOV$ERROR.MESSAGE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV$ERROR.MESSAGE[mask.fake.error] <-
"none"
#Return results
return(list(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, saved.models))
}
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###################################################################################
##############ETAs IN BASELINE & SLOPE/EC50/EMAX BOV for PERIOD######################
###################################################################################
myModeling17 <- function(myData, AIC.k, delay.confidence){
#library(nlme)
i.int <- mean(myData$RESPONSE, na.rm = TRUE)
i.amp <- sd(myData$RESPONSE, na.rm = TRUE)
i.tpeak1 <- 0
i.tpeak2 <- 0
mask.na.for.fNTAFD <-
!(myData[, "EXPOSURE"] %in% NA) &
!(myData[, "RESPONSE"] %in% NA) & !(myData[, "fNTAFD"] %in% NA)
i.fNTAFD <- rep(i.int,length(unique(myData$fNTAFD[mask.na.for.fNTAFD])))
i.slo <- 0
i.emax <- i.amp
i.ec50 <- log(mean(myData$EXPOSURE, na.rm = TRUE))
i.hill <- log(1)
dfEmpty <- data.frame(MODEL=NA, AIC=NA, SLOPE=NA, VAR.SLOPE=NA, EMAX=NA, VAR.EMAX=NA,
EC50=NA, VAR.EC50=NA, COV.EMAX.EC50=NA, HILL=NA, VAR.HILL=NA,
COV.EMAX.HILL=NA, COV.EC50.HILL=NA, DRUG.EFFECT.DELAY=NA,
ERROR.MESSAGE=NA)
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- data.frame()
saved.models = list()
#################Estimated E0############################################
##Mod02-E0+Emax
tmp <- dfEmpty
tmp$MODEL <- "91, model = e0 + emax, bsv = e0 +ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Int+Emax+EC50~1,
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(Int=i.int, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod03-E0+SigEma
tmp <- dfEmpty
tmp$MODEL <- "92, model = e0 + sigmoidal emax, bsv = e0 + ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Int+Emax+EC50+Hill~1,
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(Int=i.int, Emax=i.emax, EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Estimated E0+fNTAFD##########################################
##Mod05-E0/fNTAFD+Emax
tmp <- dfEmpty
tmp$MODEL <- "93, model = e0~fNTAFD + emax, bsv = e0 + ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=list(Int~fNTAFD-1, Emax+EC50~1),
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(i.fNTAFD, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod06-E0/fNTAFD+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "94, model = e0~fNTAFD + sigmoidal emax, bsv = e0 + ec50 + emax, bov = e0"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.intercept.fun(Int)+.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=list(Int~fNTAFD-1, Emax+EC50+Hill~1),
random=list(ID=Int+EC50+Emax~1, PERIOD=Int~1),
start=c(i.fNTAFD, Emax=i.emax, EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Cosine Period 24h############################################
##Mod08-Cos24+Emax
tmp <- dfEmpty
tmp$MODEL <- "95, model = cosine 24 h period + emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine24.fun(Mean, Amp1, Tpeak1, TOD=TOD)+
.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Emax+EC50~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Emax=i.emax,
EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod09-Cos24+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "96, model = cosine 24 h period + sigmoidal emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine24.fun(Mean, Amp1, Tpeak1, TOD=TOD)+
.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Emax+EC50+Hill~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Emax=i.emax,
EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Cosine Period 12h############################################
##Mod11-Cos12+Emax
tmp <- dfEmpty
tmp$MODEL <- "97, model = cosine 12 h period + emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine12.fun(Mean, Amp2, Tpeak2, TOD=TOD)+
.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp2+Tpeak2+Emax+EC50~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp2=i.amp, Tpeak2=i.tpeak2, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod12-Cos12+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "98, model = cosine 12 h period + sigmoidal emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.cosine12.fun(Mean, Amp2, Tpeak2, TOD=TOD)+
.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp2+Tpeak2+Emax+EC50+Hill~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp2=i.amp, Tpeak2=i.tpeak2, Emax=i.emax,
EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#################Double Cosine############################################
##Mod14-Dcos+Emax
tmp <- dfEmpty
tmp$MODEL <- "99, model = double cosine + emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.dcosine.fun(Mean, Amp1, Tpeak1, Amp2, Tpeak2, TOD=TOD)+
.my.Emax.fun(Emax, EC50, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Amp2+Tpeak2+Emax+EC50~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Amp2=i.amp,
Tpeak2=i.tpeak2, Emax=i.emax, EC50=i.ec50),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
##Mod15-Dcos+SigEmax
tmp <- dfEmpty
tmp$MODEL <- "100, model = double cosine + sigmoidal emax, bsv = mean + ec50 + emax, bov = mean"
suppressWarnings(try({
my.nlme <- nlme(RESPONSE~.my.dcosine.fun(Mean, Amp1, Tpeak1, Amp2, Tpeak2, TOD=TOD)+
.my.sigEmax.fun(Emax, EC50, Hill, Conc=EXPOSURE),
data=myData,
fixed=Mean+Amp1+Tpeak1+Amp2+Tpeak2+Emax+EC50+Hill~1,
random=list(ID=Mean+EC50+Emax~1, PERIOD=Mean~1),
start=c(Mean=i.int, Amp1=i.amp, Tpeak1=i.tpeak1, Amp2=i.amp,
Tpeak2=i.tpeak2, Emax=i.emax, EC50=i.ec50, Hill=i.hill),
na.action=na.omit)
extract <- extract.param.cov(my.nlme, c("Emax", "EC50", "Hill"))
extract.num <- as.numeric(extract)
names(extract.num) <- names(extract)
tmp$AIC <- AIC(my.nlme, k = AIC.k)
tmp$EMAX <- extract.num["value.Emax"]
tmp$EC50 <- extract.num["value.EC50"]
tmp$HILL <- extract.num["value.Hill"]
tmp$VAR.EMAX <- extract.num["cov.Emax.Emax"]
tmp$VAR.EC50 <- extract.num["cov.EC50.EC50"]
tmp$VAR.HILL <- extract.num["cov.Hill.Hill"]
tmp$COV.EMAX.EC50 <- extract.num["cov.Emax.EC50"]
tmp$COV.EMAX.HILL <- extract.num["cov.Emax.Hill"]
tmp$COV.EC50.HILL <- extract.num["cov.EC50.Hill"]
tmp$DRUG.EFFECT.DELAY <- cder.regression(myData, my.nlme, delay.confidence)
saved.models[[tmp$MODEL]] = my.nlme
}, silent = T))
tmp$ERROR.MESSAGE <- geterrmessage()
try(stop(""),TRUE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV <- rbind(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, tmp)
#Replace fake error by none
mask.fake.error <- grep("try", results.nlme.ETA.BL.SLO.EC50.EMAX.BOV$ERROR.MESSAGE)
results.nlme.ETA.BL.SLO.EC50.EMAX.BOV$ERROR.MESSAGE[mask.fake.error] <-
"none"
#Return results
return(list(results.nlme.ETA.BL.SLO.EC50.EMAX.BOV, saved.models))
}
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