This is a methods to simulate dose escalation procedure using both DLE and efficacy responses. This is a method based on the DualResponsesDesign where DLEmodel used are of ModelTox class object and efficacy model used are of ModelEff class object. In addition, no DLE and efficacy samples are involved or generated in the simulation process
This is a methods to simulate dose escalation procedure using both DLE and efficacy responses.
This is a method based on the DualResponsesDesign
where DLEmodel used are of
ModelTox
class object and efficacy model used are of ModelEff
class object. In addition, no DLE and efficacy samples are involved or generated in the simulation
process
## S4 method for signature 'DualResponsesDesign' simulate(object, nsim = 1L, seed = NULL, trueDLE, trueEff, trueNu, args = NULL, firstSeparate = FALSE, parallel = FALSE, nCores = min(parallel::detectCores(), 5), ...)
object |
the |
nsim |
the number of simulations (default :1) |
seed |
see |
trueDLE |
a function which takes as input a dose (vector) and returns the true probability
(vector) of the occurrence of a DLE. Additional arguments can be supplied in |
trueEff |
a function which takes as input a dose (vector) and returns the expected efficacy
responses (vector). Additional arguments can be supplied in |
trueNu |
the precision, the inverse of the variance of the efficacy responses |
args |
data frame with arguments for the |
firstSeparate |
enroll the first patient separately from the rest of the cohort? (not default) If yes, the cohort will be closed if a DLT occurs in this patient. |
parallel |
should the simulation runs be parallelized across the clusters of the computer? (not default) |
nCores |
how many cores should be used for parallel computing? Defaults to the number of cores on the machine, maximum 5. |
... |
not used |
an object of class PseudoDualSimulations
##Simulate dose-escalation procedure based on DLE and efficacy responses where no DLE ## and efficacy samples are used ## we need a data object with doses >= 1: 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 'NextBestMaxGain' class mynextbest<-NextBestMaxGain(DLEDuringTrialtarget=0.35, DLEEndOfTrialtarget=0.3) ##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 36 subjects are treated myStopping <- StoppingMinPatients(nPatients=36) ##Now specified the design with all the above information and starting with a dose of 25 ##Specified the design(for details please refer to the 'DualResponsesDesign' example) design <- DualResponsesDesign(nextBest=mynextbest, model=DLEmodel, Effmodel=Effmodel, stopping=myStopping, increments=myIncrements, cohortSize=mySize, data=data,startingDose=25) ##Specify the true DLE and efficacy curves myTruthDLE<- function(dose) { DLEmodel@prob(dose, 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)))))} ## Then specified the simulations and generate the trial ##For illustration purpose only 1 simulation is produced (nsim=1). options<-McmcOptions(burnin=100,step=2,samples=200) mySim <-simulate(object=design, args=NULL, trueDLE=myTruthDLE, trueEff=myTruthEff, trueNu=1/0.025, nsim=1, seed=819, parallel=FALSE)
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