Obtain hypothetical trial course table for a design
This generic function takes a design and generates a dataframe showing the beginning of several hypothetical trial courses under the design. This means, from the generated dataframe one can read off: - how many cohorts are required in the optimal case (no DLTs observed) in order to reach the highest dose of the specified dose grid (or until the stopping rule is fulfilled) - assuming no DLTs are observed until a certain dose level, what the next recommended dose is for all possible number of DLTs observed - the actual relative increments that will be used in these cases - whether the trial would stop at a certain cohort Examining the "single trial" behavior of a dose escalation design is the first important step in evaluating a design, and cannot be replaced by studying solely the operating characteristics in "many trials". The cohort sizes are also taken from the design, assuming no DLTs occur until the dose listed.
examine(object, ..., maxNoIncrement = 100L) ## S4 method for signature 'Design' examine(object, mcmcOptions = McmcOptions(), ..., maxNoIncrement) ## S4 method for signature 'RuleDesign' examine(object, ..., maxNoIncrement = 100L)
object |
the design ( |
... |
additional arguments (see methods) |
maxNoIncrement |
maximum number of contiguous next doses at 0 DLTs that are the same as before, i.e. no increment (default to 100) |
mcmcOptions |
object of class |
The data frame
Design
: Examine a model-based CRM
RuleDesign
: Examine a rule-based design
# Define the dose-grid emptydata <- Data(doseGrid = c(1, 3, 5, 10, 15, 20, 25)) # Initialize the CRM model model <- LogisticLogNormal(mean=c(-0.85, 1), cov= matrix(c(1, -0.5, -0.5, 1), nrow=2), refDose=56) # Choose the rule for selecting the next dose myNextBest <- NextBestNCRM(target=c(0.2, 0.35), overdose=c(0.35, 1), maxOverdoseProb=0.25) # Choose the rule for the cohort-size mySize1 <- CohortSizeRange(intervals=c(0, 30), cohortSize=c(1, 3)) mySize2 <- CohortSizeDLT(DLTintervals=c(0, 1), cohortSize=c(1, 3)) mySize <- maxSize(mySize1, mySize2) # Choose the rule for stopping myStopping1 <- StoppingMinCohorts(nCohorts=3) myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35), prob=0.5) myStopping3 <- StoppingMinPatients(nPatients=20) myStopping <- (myStopping1 & myStopping2) | myStopping3 # Choose the rule for dose increments myIncrements <- IncrementsRelative(intervals=c(0, 20), increments=c(1, 0.33)) # Initialize the design design <- Design(model=model, nextBest=myNextBest, stopping=myStopping, increments=myIncrements, cohortSize=mySize, data=emptydata, startingDose=3) # Examine the design set.seed(4235) # MCMC parameters are set to small values only to show this example. They should be # increased for a real case. options <- McmcOptions(burnin=10,step=1,samples=20) examine(design, options) ## example where examine stops because stopping rule already fulfilled myStopping4 <- StoppingMinPatients(nPatients=3) myStopping <- (myStopping1 & myStopping2) | myStopping4 design <- Design(model=model, nextBest=myNextBest, stopping=myStopping, increments=myIncrements, cohortSize=mySize, data=emptydata, startingDose=3) examine(design,mcmcOptions=options) ## example where examine stops because infinite looping ## (note that here a very low threshold is used for the parameter ## "maxNoIncrement" in "examine" to keep the execution time short) myIncrements <- IncrementsRelative(intervals=c(0, 20), increments=c(1, 0.00001)) myStopping <- (myStopping1 & myStopping2) design <- Design(model=model, nextBest=myNextBest, stopping=myStopping, increments=myIncrements, cohortSize=mySize, data=emptydata, startingDose=3) examine(design, mcmcOptions=options, maxNoIncrement = 2) # Define the dose-grid emptydata <- Data(doseGrid = c(5, 10, 15, 25, 35, 50, 80)) # inizialing a 3+3 design with constant cohort size of 3 and # starting dose equal 5 myDesign <- RuleDesign(nextBest = NextBestThreePlusThree(), cohortSize = CohortSizeConst(size=3L), data = emptydata, startingDose = 5) # Examine the design set.seed(4235) examine(myDesign)
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