SubTite (version 3.0.2)

GetSubTite: Gives the subgroup specific optimal dose vector. Returns a list containing the optimal doses to enroll each subgroup at and the subgroups that should have their accrual suspended temporarily.

Description

Gives the subgroup specific optimal dose vector. Returns a list containing the optimal doses to enroll each subgroup at and the subgroups that should have their accrual suspended temporarily.

Usage

GetSubTite(Y, I, Doses, Groups, DoseTried, cohort, T1, Target, Upper, Dose,
  meanmu, meanslope, MeanInts, MeanSlopes, varint, varbeta, phetero,
  Borrow, B)

Arguments

Y

Vector containing observed event or censoring times.

I

Vector containing event indicators (1 if patient experiences an event for a patient).

Doses

Vector containing Doses of patients in trial.

Groups

Vector containing group assignment of patients, 1 is baseline group.

DoseTried

Matrix that contains counts in each subgroup for the number of times each dose has been assigned.

cohort

Number of patients needed to be assigned at a dose level prior to escalation.

T1

Reference time for toxicity.

Target

Target cumulative toxicity probability vector at time T1.

Upper

Cutoff values used to determine if accrual in a subgroup should be suspended.

Dose

Vector containing the standardized doses considered.

meanmu

Prior mean for baseline intercept.

meanslope

Prior mean for baseline slope.

MeanInts

Vector of prior means for the group specific intercept parameters.

MeanSlopes

Vector of prior means for the group specific slope parameters.

varint

Prior variance for the intercept parameters.

varbeta

Prior variance for the slope parameters.

phetero

Prior probability of heterogeneous subgroups.

Borrow

Parameter to specify subgroup borrowing/clustering. 0=No borrowing, 1=Borrowing but no clustering, 2=Borrowing and clustering.

B

Number of Iterations to run for MCMC

Value

Returns a list with two objects, a vector of optimal doses for each subgroup and matrix of posterior toxicity probabilities at each dose level within each subgroup.

References

[1] Chapple and Thall (2017), Subgroup Specific Dose Finding in Phase I Clinical Trials Based on Time to Toxicity Within a Fixed Follow Up Period.

Examples

# NOT RUN {
T1=6
## Reference Time for Toxicity
##Number of subgroups
nGroups=3
##Number of Doses
nDose=4
##What is the starting dose? We want to set all dose tried > cohort that's less than this
DoseStart=4
##Sample Size
n=90
Target=rep(.3,nGroups)
Upper=rep(.95,nGroups)
Y=rep(NA,n)
I=rep(NA,n)
Groups = sample(1:nGroups,n,replace=TRUE) - 1
##Group assignment of patients (MUST BE CODED 0,1,2,...)
Doses = sample(1:DoseStart,n,replace=TRUE)
Dose2=Doses ##Going to hold the numeric dose numbers
##Randomly Generate Dose values
x=sort(runif(nDose))  ##Doses are in ascending order
Dose=(x-mean(x))/sd(x)
##Vector of standardized doses
##Randomly generate TRUE group probabilties
GroupProb = matrix(ncol=nDose,nrow=nGroups)
for(k in 1:nGroups){
GroupProb[k,]=sort(runif(nDose,0,Target[k]+.2))
}
##Randomly generate patient data from a uniform TTE dist with given probabilities.
for(b in 1:n){
I[b]= rbinom(1,1   , GroupProb[(Groups[b]+1),Dose2[b]])
if(I[b]==0){ Y[b]=T1 }else{ Y[b]=runif(1,0,T1) }}
##How many patients in each subgroup have been assigned at each dose level?
DoseTried=cbind(table(Groups,Doses))
cohort=1 ##Cohort size required for escalation
##Matrix of umber of patients tried or fully evaluated at each dose level.
DoseTried[,1:DoseStart]=cohort
##Hyperparameters
meanmu=-0.4467184 ##Common Intercept hypermean
meanslope= 0.8861634 ##Common slope hypermean
MeanInts = rep(-0.5205379,nGroups-1) ##Group Intercept hypermeans
MeanSlopes = rep(0.1888923,nGroups-1) ##Group slope hyperneabs
Dose2=Doses ##Numeric Doses
Doses=Dose[Doses]  ##Standardize dose value
varint=5 #Prior Variance of the intercept betas
varbeta=1 ##Prior Variance of slope betas
phetero=.9 ##Prior Probability of hetergeneity
Borrow=0 ##Borrowing specification, 0=none, 1=some, 2=clustering.
B=5000 ##Number of iterations
Borrow=2
GetSubTite(Y, I,Doses, Groups, DoseTried,cohort, T1,
        Target,  Upper, Dose,  meanmu, meanslope,
       MeanInts,  MeanSlopes ,varint,varbeta,phetero, Borrow,B)
# }