stopTrial: Stop the trial?
In crmPack: Object-Oriented Implementation of CRM Designs
stopTrial R Documentation
Stop the trial?
Description
This function returns whether to stop the trial.
Usage
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingList,ANY,ANY,ANY,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingAll,ANY,ANY,ANY,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingAny,ANY,ANY,ANY,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingCohortsNearDose,numeric,ANY,ANY,Data'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingPatientsNearDose,numeric,ANY,ANY,Data'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingMinCohorts,ANY,ANY,ANY,Data'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingMinPatients,ANY,ANY,ANY,Data'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingTargetProb,numeric,Samples,Model,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingMTDdistribution,numeric,Samples,Model,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature
## 'StoppingTargetBiomarker,numeric,Samples,DualEndpoint,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingHighestDose,numeric,ANY,ANY,Data'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingTDCIRatio,ANY,Samples,ModelTox,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingTDCIRatio,ANY,missing,ModelTox,ANY'
stopTrial(stopping, dose, samples, model, data, ...)
## S4 method for signature 'StoppingGstarCIRatio,ANY,Samples,ModelTox,DataDual'
stopTrial(
stopping,
dose,
samples,
model,
data,
TDderive,
Effmodel,
Effsamples,
Gstarderive,
...
)
## S4 method for signature 'StoppingGstarCIRatio,ANY,missing,ModelTox,DataDual'
stopTrial(stopping, dose, model, data, Effmodel, ...)
Arguments
stopping
The rule, an object of class
Stopping
dose
the recommended next best dose
samples
the Samples object
model
The model input, an object of class Model
data
The data input, an object of class Data
...
additional arguments
TDderive
the function which derives from the input, a vector of the posterior samples called
TDsamples of the dose
which has the probability of the occurrence of DLE equals to either the targetDuringTrial or
targetEndOfTrial, the final next best TDtargetDuringTrial (the dose with probability of the
occurrence of DLE equals to the targetDuringTrial)and TDtargetEndOfTrial estimate.
Effmodel
the efficacy model of ModelEff class object
Effsamples
the efficacy samples of Samples class object
Gstarderive
the function which derives from the input, a vector of the posterior Gstar (the dose
which gives the maximum gain value) samples
called Gstarsamples, the final next best Gstar estimate.
Value
logical value: TRUE if the trial can be stopped, FALSE
otherwise. It should have an attribute message which gives the reason
for the decision.
Functions
-
stopTrial(
stopping = StoppingList,
dose = ANY,
samples = ANY,
model = ANY,
data = ANY
): Stop based on multiple stopping rules
-
stopTrial(
stopping = StoppingAll,
dose = ANY,
samples = ANY,
model = ANY,
data = ANY
): Stop based on fulfillment of all multiple stopping
rules
-
stopTrial(
stopping = StoppingAny,
dose = ANY,
samples = ANY,
model = ANY,
data = ANY
): Stop based on fulfillment of any stopping rule
-
stopTrial(
stopping = StoppingCohortsNearDose,
dose = numeric,
samples = ANY,
model = ANY,
data = Data
): Stop based on number of cohorts near to next best dose
-
stopTrial(
stopping = StoppingPatientsNearDose,
dose = numeric,
samples = ANY,
model = ANY,
data = Data
): Stop based on number of patients near to next best
dose
-
stopTrial(
stopping = StoppingMinCohorts,
dose = ANY,
samples = ANY,
model = ANY,
data = Data
): Stop based on minimum number of cohorts
-
stopTrial(
stopping = StoppingMinPatients,
dose = ANY,
samples = ANY,
model = ANY,
data = Data
): Stop based on minimum number of patients
-
stopTrial(
stopping = StoppingTargetProb,
dose = numeric,
samples = Samples,
model = Model,
data = ANY
): Stop based on probability of target tox interval
-
stopTrial(
stopping = StoppingMTDdistribution,
dose = numeric,
samples = Samples,
model = Model,
data = ANY
): Stop based on MTD distribution
-
stopTrial(
stopping = StoppingTargetBiomarker,
dose = numeric,
samples = Samples,
model = DualEndpoint,
data = ANY
): Stop based on probability of targeting biomarker
-
stopTrial(
stopping = StoppingHighestDose,
dose = numeric,
samples = ANY,
model = ANY,
data = Data
): Stop when the highest dose is reached
-
stopTrial(
stopping = StoppingTDCIRatio,
dose = ANY,
samples = Samples,
model = ModelTox,
data = ANY
): Stop based on 'StoppingTDCIRatio' class when
reaching the target ratio of the upper to the lower 95
interval of the estimate (TDtargetEndOfTrial). This is a stopping rule which incorporate only
DLE responses and DLE samples are given
-
stopTrial(
stopping = StoppingTDCIRatio,
dose = ANY,
samples = missing,
model = ModelTox,
data = ANY
): Stop based on 'StoppingTDCIRatio' class
when reaching the target ratio of the upper to the lower 95
interval of the estimate (TDtargetEndOfTrial). This is a stopping rule which incorporate only
DLE responses and no DLE samples are involved
-
stopTrial(
stopping = StoppingGstarCIRatio,
dose = ANY,
samples = Samples,
model = ModelTox,
data = DataDual
): Stop based on reaching the target ratio of the upper to the lower 95
interval of the estimate (the minimum of Gstar and TDtargetEndOfTrial). This is a stopping rule which
incorporate DLE and efficacy responses and DLE and efficacy samples are also used.
-
stopTrial(
stopping = StoppingGstarCIRatio,
dose = ANY,
samples = missing,
model = ModelTox,
data = DataDual
): Stop based on reaching the target ratio of the upper to the lower 95
interval of the estimate (the minimum of Gstar and TDtargetEndOfTrial). This is a stopping rule which
incorporate DLE and efficacy responses without DLE and efficacy samples involved.
Examples
## Example of combining stopping rules with '&' and/or '|' operators
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
myStopping <- (myStopping1 & myStopping2) | myStopping3
# Create some data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rules
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
# Create a list of stopping rules (of class 'StoppingList') which will then be
# summarized (in this specific example) with the 'any' function, meaning that the study
# would be stopped if 'any' of the single stopping rules is TRUE.
mystopping <- StoppingList(stopList=c(myStopping1,myStopping2,myStopping3),
summary=any)
# Evaluate if to stop the Trial
stopTrial(stopping=myStopping, dose=doseRecommendation$value,
samples=samples, model=model, data=data)
# Create some data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rules
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
# Combine the stopping rules, obtaining (in this specific example) a list of stopping
# rules of class 'StoppingAll'
myStopping <- (myStopping1 | myStopping2) & myStopping3
# Evaluate if to stop the Trial
stopTrial(stopping=myStopping, dose=doseRecommendation$value,
samples=samples, model=model, data=data)
# Create some data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rules
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
# Combine the stopping rules, obtaining (in this specific example) a list of stopping
# rules of class 'StoppingAny'
myStopping <- (myStopping1 | myStopping2) | myStopping3
# Evaluate if to stop the Trial
stopTrial(stopping=myStopping, dose=doseRecommendation$value,
samples=samples, model=model, data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 3
# cohorts were already dosed within 1 +/- 0.2 of the next best dose
myStopping <- StoppingCohortsNearDose(nCohorts = 3,
percentage = 0.2)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 9
# patients were already dosed within 1 +/- 0.2 of the next best dose
myStopping <- StoppingPatientsNearDose(nPatients = 9,
percentage = 0.2)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 6
# cohorts were already dosed
myStopping <- StoppingMinCohorts(nCohorts = 6)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 20
# patients were already dosed
myStopping <- StoppingMinPatients(nPatients = 20)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if there is at least
# 0.5 posterior probability that [0.2 =< Prob(DLT | next-best-dose) <= 0.35]
myStopping <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if there is at least
# 0.9 probability that MTD > 0.5*next_best_dose. Here MTD is defined as the dose for
# which prob(DLE)=0.33
myStopping <- StoppingMTDdistribution(target = 0.33,
thresh = 0.5,
prob = 0.9)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
# Create the data
data <- DataDual(
x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10,
20, 20, 20, 40, 40, 40, 50, 50, 50),
y=c(0, 0, 0, 0, 0, 0, 1, 0,
0, 1, 1, 0, 0, 1, 0, 1, 1),
w=c(0.31, 0.42, 0.59, 0.45, 0.6, 0.7, 0.55, 0.6,
0.52, 0.54, 0.56, 0.43, 0.41, 0.39, 0.34, 0.38, 0.21),
doseGrid=c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the Dual-Endpoint model (in this case RW1)
model <- DualEndpointRW(mu = c(0, 1),
Sigma = matrix(c(1, 0, 0, 1), nrow=2),
sigma2betaW = 0.01,
sigma2W = c(a=0.1, b=0.1),
rho = c(a=1, b=1),
smooth = "RW1")
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=500)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# In this case target a dose achieving at least 0.9 of maximum biomarker level (efficacy)
# and with a probability below 0.25 that prob(DLT)>0.35 (safety)
myNextBest <- NextBestDualEndpoint(target=c(0.9, 1),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples,
model=model,
data=data)
# Define the stopping rule such that the study would be stopped if if there is at
# least 0.5 posterior probability that the biomarker (efficacy) is within the
# biomarker target range of [0.9, 1.0] (relative to the maximum for the biomarker).
myStopping <- StoppingTargetBiomarker(target = c(0.9, 1),
prob = 0.5)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10, 20, 20, 20, 40, 40, 40,
80, 80, 80),
y=c(0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5, 6, 6, 6, 7, 7, 7, 8, 8, 8),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if there is at least
# 0.5 posterior probability that [0.2 =< Prob(DLT | next-best-dose) <= 0.35]
stopTarget <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
## now use the StoppingHighestDose rule:
stopHigh <-
StoppingHighestDose() &
StoppingPatientsNearDose(nPatients=3, percentage=0) &
StoppingTargetProb(target=c(0, 0.2),
prob=0.5)
## and combine everything:
myStopping <- stopTarget | stopHigh
# Then evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
##define the stopping rules based on the 'StoppingTDCIRatio' class
##Using only DLE responses with samples
## we need a data object with doses >= 1:
data<-Data(x=c(25,50,50,75,150,200,225,300),
y=c(0,0,0,0,1,1,1,1),
doseGrid=seq(from=25,to=300,by=25))
##model can be specified of 'Model' or 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
model<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##define MCMC options
##for illustration purpose we use 10 burn-in and generate 50 samples
options<-McmcOptions(burnin=10,step=2,samples=50)
##samples of 'Samples' class
samples<-mcmc(data,model,options)
##define the 'StoppingTDCIRatio' class
myStopping <- StoppingTDCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
tdNextBest<-NextBestTDsamples(targetDuringTrial=0.35,targetEndOfTrial=0.3,
derive=function(TDsamples){quantile(TDsamples,probs=0.3)})
RecommendDose<-nextBest(tdNextBest,doselimit=max(data@doseGrid),samples=samples,
model=model,data=data)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,dose=RecommendDose$nextdose,
samples=samples,model=model,data=data)
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
##define the stopping rules based on the 'StoppingTDCIRatio' class
##Using only DLE responses
## we need a data object with doses >= 1:
data<-Data(x=c(25,50,50,75,150,200,225,300),
y=c(0,0,0,0,1,1,1,1),
doseGrid=seq(from=25,to=300,by=25))
##model must be of 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
model<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##define the 'StoppingTDCIRatio' class
myStopping <- StoppingTDCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
tdNextBest<-NextBestTD(targetDuringTrial=0.35,targetEndOfTrial=0.3)
RecommendDose<-nextBest(tdNextBest,doselimit=max(data@doseGrid),model=model,data=data)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,dose=RecommendDose$nextdose,
model=model,data=data)
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
##define the stopping rules based on the 'StoppingGstarCIRatio' class
##Using both DLE and efficacy responses
## we need a data object with doses >= 1:
data <-DataDual(x=c(25,50,25,50,75,300,250,150),
y=c(0,0,0,0,0,1,1,0),
w=c(0.31,0.42,0.59,0.45,0.6,0.7,0.6,0.52),
doseGrid=seq(25,300,25),
placebo=FALSE)
##DLEmodel must be of 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
DLEmodel<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##Effmodel must be of 'ModelEff' class
##For example, the 'Effloglog' class model
Effmodel<-Effloglog(Eff=c(1.223,2.513),Effdose=c(25,300),nu=c(a=1,b=0.025),data=data,c=0)
##for illustration purpose we use 10 burn-in and generate 50 samples
options<-McmcOptions(burnin=10,step=2,samples=50)
##DLE and efficacy samples must be of 'Samples' class
DLEsamples<-mcmc(data,DLEmodel,options)
Effsamples<-mcmc(data,Effmodel,options)
##define the 'StoppingGstarCIRatio' class
myStopping <- StoppingGstarCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
mynextbest<-NextBestMaxGainSamples(DLEDuringTrialtarget=0.35,
DLEEndOfTrialtarget=0.3,
TDderive=function(TDsamples){
quantile(TDsamples,prob=0.3)},
Gstarderive=function(Gstarsamples){
quantile(Gstarsamples,prob=0.5)})
RecommendDose<-nextBest(mynextbest,doselimit=max(data@doseGrid),samples=DLEsamples,model=DLEmodel,
data=data,Effmodel=Effmodel,Effsamples=Effsamples)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,
dose=RecommendDose$nextdose,
samples=DLEsamples,
model=DLEmodel,
data=data,
TDderive=function(TDsamples){
quantile(TDsamples,prob=0.3)},
Effmodel=Effmodel,
Effsamples=Effsamples,
Gstarderive=function(Gstarsamples){
quantile(Gstarsamples,prob=0.5)})
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
##define the stopping rules based on the 'StoppingGstarCIRatio' class
##Using both DLE and efficacy responses
## we need a data object with doses >= 1:
data <-DataDual(x=c(25,50,25,50,75,300,250,150),
y=c(0,0,0,0,0,1,1,0),
w=c(0.31,0.42,0.59,0.45,0.6,0.7,0.6,0.52),
doseGrid=seq(25,300,25),
placebo=FALSE)
##DLEmodel must be of 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
DLEmodel<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##Effmodel must be of 'ModelEff' class
##For example, the 'Effloglog' class model
Effmodel<-Effloglog(Eff=c(1.223,2.513),Effdose=c(25,300),nu=c(a=1,b=0.025),data=data,c=0)
##define the 'StoppingGstarCIRatio' class
myStopping <- StoppingGstarCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
mynextbest<-NextBestMaxGain(DLEDuringTrialtarget=0.35,DLEEndOfTrialtarget=0.3)
RecommendDose<-nextBest(mynextbest,doselimit=max(data@doseGrid),model=DLEmodel,
Effmodel=Effmodel,data=data)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,dose=RecommendDose$nextdose,model=DLEmodel,
data=data, Effmodel=Effmodel)
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
crmPack documentation built on Sept. 3, 2022, 1:05 a.m.
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| stopTrial | R Documentation |
Stop the trial?
Description
This function returns whether to stop the trial.
Usage
stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingList,ANY,ANY,ANY,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingAll,ANY,ANY,ANY,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingAny,ANY,ANY,ANY,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingCohortsNearDose,numeric,ANY,ANY,Data' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingPatientsNearDose,numeric,ANY,ANY,Data' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingMinCohorts,ANY,ANY,ANY,Data' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingMinPatients,ANY,ANY,ANY,Data' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingTargetProb,numeric,Samples,Model,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingMTDdistribution,numeric,Samples,Model,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature ## 'StoppingTargetBiomarker,numeric,Samples,DualEndpoint,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingHighestDose,numeric,ANY,ANY,Data' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingTDCIRatio,ANY,Samples,ModelTox,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingTDCIRatio,ANY,missing,ModelTox,ANY' stopTrial(stopping, dose, samples, model, data, ...) ## S4 method for signature 'StoppingGstarCIRatio,ANY,Samples,ModelTox,DataDual' stopTrial( stopping, dose, samples, model, data, TDderive, Effmodel, Effsamples, Gstarderive, ... ) ## S4 method for signature 'StoppingGstarCIRatio,ANY,missing,ModelTox,DataDual' stopTrial(stopping, dose, model, data, Effmodel, ...)
Arguments
stopping |
The rule, an object of class
|
dose |
the recommended next best dose |
samples |
the |
model |
The model input, an object of class |
data |
The data input, an object of class |
... |
additional arguments |
TDderive |
the function which derives from the input, a vector of the posterior samples called
|
Effmodel |
the efficacy model of |
Effsamples |
the efficacy samples of |
Gstarderive |
the function which derives from the input, a vector of the posterior Gstar (the dose
which gives the maximum gain value) samples
called |
Value
logical value: TRUE if the trial can be stopped, FALSE
otherwise. It should have an attribute message which gives the reason
for the decision.
Functions
-
stopTrial( stopping = StoppingList, dose = ANY, samples = ANY, model = ANY, data = ANY ): Stop based on multiple stopping rules -
stopTrial( stopping = StoppingAll, dose = ANY, samples = ANY, model = ANY, data = ANY ): Stop based on fulfillment of all multiple stopping rules -
stopTrial( stopping = StoppingAny, dose = ANY, samples = ANY, model = ANY, data = ANY ): Stop based on fulfillment of any stopping rule -
stopTrial( stopping = StoppingCohortsNearDose, dose = numeric, samples = ANY, model = ANY, data = Data ): Stop based on number of cohorts near to next best dose -
stopTrial( stopping = StoppingPatientsNearDose, dose = numeric, samples = ANY, model = ANY, data = Data ): Stop based on number of patients near to next best dose -
stopTrial( stopping = StoppingMinCohorts, dose = ANY, samples = ANY, model = ANY, data = Data ): Stop based on minimum number of cohorts -
stopTrial( stopping = StoppingMinPatients, dose = ANY, samples = ANY, model = ANY, data = Data ): Stop based on minimum number of patients -
stopTrial( stopping = StoppingTargetProb, dose = numeric, samples = Samples, model = Model, data = ANY ): Stop based on probability of target tox interval -
stopTrial( stopping = StoppingMTDdistribution, dose = numeric, samples = Samples, model = Model, data = ANY ): Stop based on MTD distribution -
stopTrial( stopping = StoppingTargetBiomarker, dose = numeric, samples = Samples, model = DualEndpoint, data = ANY ): Stop based on probability of targeting biomarker -
stopTrial( stopping = StoppingHighestDose, dose = numeric, samples = ANY, model = ANY, data = Data ): Stop when the highest dose is reached -
stopTrial( stopping = StoppingTDCIRatio, dose = ANY, samples = Samples, model = ModelTox, data = ANY ): Stop based on 'StoppingTDCIRatio' class when reaching the target ratio of the upper to the lower 95 interval of the estimate (TDtargetEndOfTrial). This is a stopping rule which incorporate only DLE responses and DLE samples are given -
stopTrial( stopping = StoppingTDCIRatio, dose = ANY, samples = missing, model = ModelTox, data = ANY ): Stop based on 'StoppingTDCIRatio' class when reaching the target ratio of the upper to the lower 95 interval of the estimate (TDtargetEndOfTrial). This is a stopping rule which incorporate only DLE responses and no DLE samples are involved -
stopTrial( stopping = StoppingGstarCIRatio, dose = ANY, samples = Samples, model = ModelTox, data = DataDual ): Stop based on reaching the target ratio of the upper to the lower 95 interval of the estimate (the minimum of Gstar and TDtargetEndOfTrial). This is a stopping rule which incorporate DLE and efficacy responses and DLE and efficacy samples are also used. -
stopTrial( stopping = StoppingGstarCIRatio, dose = ANY, samples = missing, model = ModelTox, data = DataDual ): Stop based on reaching the target ratio of the upper to the lower 95 interval of the estimate (the minimum of Gstar and TDtargetEndOfTrial). This is a stopping rule which incorporate DLE and efficacy responses without DLE and efficacy samples involved.
Examples
## Example of combining stopping rules with '&' and/or '|' operators
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
myStopping <- (myStopping1 & myStopping2) | myStopping3
# Create some data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rules
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
# Create a list of stopping rules (of class 'StoppingList') which will then be
# summarized (in this specific example) with the 'any' function, meaning that the study
# would be stopped if 'any' of the single stopping rules is TRUE.
mystopping <- StoppingList(stopList=c(myStopping1,myStopping2,myStopping3),
summary=any)
# Evaluate if to stop the Trial
stopTrial(stopping=myStopping, dose=doseRecommendation$value,
samples=samples, model=model, data=data)
# Create some data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rules
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
# Combine the stopping rules, obtaining (in this specific example) a list of stopping
# rules of class 'StoppingAll'
myStopping <- (myStopping1 | myStopping2) & myStopping3
# Evaluate if to stop the Trial
stopTrial(stopping=myStopping, dose=doseRecommendation$value,
samples=samples, model=model, data=data)
# Create some data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rules
myStopping1 <- StoppingMinCohorts(nCohorts=3)
myStopping2 <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
myStopping3 <- StoppingMinPatients(nPatients=20)
# Combine the stopping rules, obtaining (in this specific example) a list of stopping
# rules of class 'StoppingAny'
myStopping <- (myStopping1 | myStopping2) | myStopping3
# Evaluate if to stop the Trial
stopTrial(stopping=myStopping, dose=doseRecommendation$value,
samples=samples, model=model, data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 3
# cohorts were already dosed within 1 +/- 0.2 of the next best dose
myStopping <- StoppingCohortsNearDose(nCohorts = 3,
percentage = 0.2)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 9
# patients were already dosed within 1 +/- 0.2 of the next best dose
myStopping <- StoppingPatientsNearDose(nPatients = 9,
percentage = 0.2)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 6
# cohorts were already dosed
myStopping <- StoppingMinCohorts(nCohorts = 6)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if at least 20
# patients were already dosed
myStopping <- StoppingMinPatients(nPatients = 20)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if there is at least
# 0.5 posterior probability that [0.2 =< Prob(DLT | next-best-dose) <= 0.35]
myStopping <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10),
y=c(0, 0, 0, 0, 0, 0, 1, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if there is at least
# 0.9 probability that MTD > 0.5*next_best_dose. Here MTD is defined as the dose for
# which prob(DLE)=0.33
myStopping <- StoppingMTDdistribution(target = 0.33,
thresh = 0.5,
prob = 0.9)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
# Create the data
data <- DataDual(
x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10,
20, 20, 20, 40, 40, 40, 50, 50, 50),
y=c(0, 0, 0, 0, 0, 0, 1, 0,
0, 1, 1, 0, 0, 1, 0, 1, 1),
w=c(0.31, 0.42, 0.59, 0.45, 0.6, 0.7, 0.55, 0.6,
0.52, 0.54, 0.56, 0.43, 0.41, 0.39, 0.34, 0.38, 0.21),
doseGrid=c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the Dual-Endpoint model (in this case RW1)
model <- DualEndpointRW(mu = c(0, 1),
Sigma = matrix(c(1, 0, 0, 1), nrow=2),
sigma2betaW = 0.01,
sigma2W = c(a=0.1, b=0.1),
rho = c(a=1, b=1),
smooth = "RW1")
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=500)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# In this case target a dose achieving at least 0.9 of maximum biomarker level (efficacy)
# and with a probability below 0.25 that prob(DLT)>0.35 (safety)
myNextBest <- NextBestDualEndpoint(target=c(0.9, 1),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples,
model=model,
data=data)
# Define the stopping rule such that the study would be stopped if if there is at
# least 0.5 posterior probability that the biomarker (efficacy) is within the
# biomarker target range of [0.9, 1.0] (relative to the maximum for the biomarker).
myStopping <- StoppingTargetBiomarker(target = c(0.9, 1),
prob = 0.5)
# Evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
# Create the data
data <- Data(x=c(0.1, 0.5, 1.5, 3, 6, 10, 10, 10, 20, 20, 20, 40, 40, 40,
80, 80, 80),
y=c(0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0),
cohort=c(0, 1, 2, 3, 4, 5, 5, 5, 6, 6, 6, 7, 7, 7, 8, 8, 8),
doseGrid=
c(0.1, 0.5, 1.5, 3, 6,
seq(from=10, to=80, by=2)))
# Initialize the CRM model used to model the data
model <- LogisticLogNormal(mean=c(-0.85, 1),
cov=
matrix(c(1, -0.5, -0.5, 1),
nrow=2),
refDose=56)
# Set-up some MCMC parameters and generate samples from the posterior
options <- McmcOptions(burnin=100,
step=2,
samples=2000)
set.seed(94)
samples <- mcmc(data, model, options)
# Define the rule for dose increments and calculate the maximum dose allowed
myIncrements <- IncrementsRelative(intervals=c(0, 20),
increments=c(1, 0.33))
nextMaxDose <- maxDose(myIncrements,
data=data)
# Define the rule which will be used to select the next best dose
# based on the class 'NextBestNCRM'
myNextBest <- NextBestNCRM(target=c(0.2, 0.35),
overdose=c(0.35, 1),
maxOverdoseProb=0.25)
# Calculate the next best dose
doseRecommendation <- nextBest(myNextBest,
doselimit=nextMaxDose,
samples=samples, model=model, data=data)
# Define the stopping rule such that the study would be stopped if there is at least
# 0.5 posterior probability that [0.2 =< Prob(DLT | next-best-dose) <= 0.35]
stopTarget <- StoppingTargetProb(target=c(0.2, 0.35),
prob=0.5)
## now use the StoppingHighestDose rule:
stopHigh <-
StoppingHighestDose() &
StoppingPatientsNearDose(nPatients=3, percentage=0) &
StoppingTargetProb(target=c(0, 0.2),
prob=0.5)
## and combine everything:
myStopping <- stopTarget | stopHigh
# Then evaluate if to stop the trial
stopTrial(stopping=myStopping,
dose=doseRecommendation$value,
samples=samples,
model=model,
data=data)
##define the stopping rules based on the 'StoppingTDCIRatio' class
##Using only DLE responses with samples
## we need a data object with doses >= 1:
data<-Data(x=c(25,50,50,75,150,200,225,300),
y=c(0,0,0,0,1,1,1,1),
doseGrid=seq(from=25,to=300,by=25))
##model can be specified of 'Model' or 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
model<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##define MCMC options
##for illustration purpose we use 10 burn-in and generate 50 samples
options<-McmcOptions(burnin=10,step=2,samples=50)
##samples of 'Samples' class
samples<-mcmc(data,model,options)
##define the 'StoppingTDCIRatio' class
myStopping <- StoppingTDCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
tdNextBest<-NextBestTDsamples(targetDuringTrial=0.35,targetEndOfTrial=0.3,
derive=function(TDsamples){quantile(TDsamples,probs=0.3)})
RecommendDose<-nextBest(tdNextBest,doselimit=max(data@doseGrid),samples=samples,
model=model,data=data)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,dose=RecommendDose$nextdose,
samples=samples,model=model,data=data)
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
##define the stopping rules based on the 'StoppingTDCIRatio' class
##Using only DLE responses
## we need a data object with doses >= 1:
data<-Data(x=c(25,50,50,75,150,200,225,300),
y=c(0,0,0,0,1,1,1,1),
doseGrid=seq(from=25,to=300,by=25))
##model must be of 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
model<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##define the 'StoppingTDCIRatio' class
myStopping <- StoppingTDCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
tdNextBest<-NextBestTD(targetDuringTrial=0.35,targetEndOfTrial=0.3)
RecommendDose<-nextBest(tdNextBest,doselimit=max(data@doseGrid),model=model,data=data)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,dose=RecommendDose$nextdose,
model=model,data=data)
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
##define the stopping rules based on the 'StoppingGstarCIRatio' class
##Using both DLE and efficacy responses
## we need a data object with doses >= 1:
data <-DataDual(x=c(25,50,25,50,75,300,250,150),
y=c(0,0,0,0,0,1,1,0),
w=c(0.31,0.42,0.59,0.45,0.6,0.7,0.6,0.52),
doseGrid=seq(25,300,25),
placebo=FALSE)
##DLEmodel must be of 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
DLEmodel<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##Effmodel must be of 'ModelEff' class
##For example, the 'Effloglog' class model
Effmodel<-Effloglog(Eff=c(1.223,2.513),Effdose=c(25,300),nu=c(a=1,b=0.025),data=data,c=0)
##for illustration purpose we use 10 burn-in and generate 50 samples
options<-McmcOptions(burnin=10,step=2,samples=50)
##DLE and efficacy samples must be of 'Samples' class
DLEsamples<-mcmc(data,DLEmodel,options)
Effsamples<-mcmc(data,Effmodel,options)
##define the 'StoppingGstarCIRatio' class
myStopping <- StoppingGstarCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
mynextbest<-NextBestMaxGainSamples(DLEDuringTrialtarget=0.35,
DLEEndOfTrialtarget=0.3,
TDderive=function(TDsamples){
quantile(TDsamples,prob=0.3)},
Gstarderive=function(Gstarsamples){
quantile(Gstarsamples,prob=0.5)})
RecommendDose<-nextBest(mynextbest,doselimit=max(data@doseGrid),samples=DLEsamples,model=DLEmodel,
data=data,Effmodel=Effmodel,Effsamples=Effsamples)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,
dose=RecommendDose$nextdose,
samples=DLEsamples,
model=DLEmodel,
data=data,
TDderive=function(TDsamples){
quantile(TDsamples,prob=0.3)},
Effmodel=Effmodel,
Effsamples=Effsamples,
Gstarderive=function(Gstarsamples){
quantile(Gstarsamples,prob=0.5)})
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
##define the stopping rules based on the 'StoppingGstarCIRatio' class
##Using both DLE and efficacy responses
## we need a data object with doses >= 1:
data <-DataDual(x=c(25,50,25,50,75,300,250,150),
y=c(0,0,0,0,0,1,1,0),
w=c(0.31,0.42,0.59,0.45,0.6,0.7,0.6,0.52),
doseGrid=seq(25,300,25),
placebo=FALSE)
##DLEmodel must be of 'ModelTox' class
##For example, the 'logisticIndepBeta' class model
DLEmodel<-LogisticIndepBeta(binDLE=c(1.05,1.8),DLEweights=c(3,3),DLEdose=c(25,300),data=data)
##Effmodel must be of 'ModelEff' class
##For example, the 'Effloglog' class model
Effmodel<-Effloglog(Eff=c(1.223,2.513),Effdose=c(25,300),nu=c(a=1,b=0.025),data=data,c=0)
##define the 'StoppingGstarCIRatio' class
myStopping <- StoppingGstarCIRatio(targetRatio=5,
targetEndOfTrial=0.3)
##Find the next Recommend dose using the nextBest method (plesae refer to nextbest examples)
mynextbest<-NextBestMaxGain(DLEDuringTrialtarget=0.35,DLEEndOfTrialtarget=0.3)
RecommendDose<-nextBest(mynextbest,doselimit=max(data@doseGrid),model=DLEmodel,
Effmodel=Effmodel,data=data)
##use 'stopTrial' to determine if the rule has been fulfilled
##use 0.3 as the target proability of DLE at the end of the trial
stopTrial(stopping=myStopping,dose=RecommendDose$nextdose,model=DLEmodel,
data=data, Effmodel=Effmodel)
## RecommendDose$nextdose refers to the next dose obtained in RecommendDose
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