Phase123 (version 2.1)

SimPhase123: Simulates replications of the phase123 and phase 12-3 trials.

Description

This function simulates replications of the phase123 and phase 12-3 trials and returns a list containing the doses chosen, decisions made (1=A(x) better, 0= futility, -1=C better)

Usage

SimPhase123(DoseStart, Dose, PE, PT, Hypermeans, Hypervars, Contour, PiLim,
  ProbLim, NET, NF, Accrue12, Time12, cohort, betaA, ProbC, betaC, Family,
  alpha, Nmax, Accrue, Twait, NLookSwitch, NLook, Sup, Fut, nSims)

Arguments

DoseStart

Starting dose of the phase 12 trial.

Dose

Vector of standardized doses considered in the trial.

PE

True efficacy dose-toxicity vector.

PT

True toxicity dose-toxicity vector.

Hypermeans

Prior Means for the Eff-Tox design of length 6.

Hypervars

Prior Variances for the Eff-Tox design of length 6.

Contour

Vector containing 4 entries used to make the desireability function. Contour[1] contains a desired toxicity probability given efficacy, Countour[2] contains a desired efficacy probability given toxicity, and (Contour[3],Contour[4]) is an equally desireable pair of efficacy and toxicity probabilities that are non-zero or one.

PiLim

Vector of length two with PiLim[1] containing the acceptable lower limit on efficacy probability and PiLim[2] containing the acceptable upper limit on toxicity probability.

ProbLim

Vector of length two with ProbLim[1] containing the probability cutoff for acceptable efficacy probability and ProbLim[2] containing the probability cutoff for acceptable toxicity probability.

NET

Maximum sample size of the phase 12 trial.

NF

Number of patients to assign deterministic doses prior to adaptive randomization.

Accrue12

Accrual rate for patients in the phase 12 portion of the trial.

Time12

Time window for phase 12.

cohort

Size of each patient cohort.

betaA

True linear term for the rate or mean parameter (beta_1,exp(beta_E),-exp(beta_T),beta_2,beta_0) for agent A.

ProbC

Probability of efficacy and toxicity for the control therapy.

betaC

Linear term for efficacy, toxicity and beta_0 for the control groupar term for efficacy, toxicity and beta_0 for the control group.

Family

Time to event distribution. Options include: Exponential, Gamma, Weibull, Lognormal.

alpha

Shape parameter or standard deviation of a lognormal distribution.

Nmax

Maximum number of patients to enroll in phase 3.

Accrue

Accrual rate for patients in the phase 3 portion of the trial.

Twait

Waiting time in between phase 12 and phase 3.

NLookSwitch

Number of patient events to determine if we re-optimize doses for A.

NLook

Vector of information criteria for making interim looks.

Sup

Vector of superiority boundaries.

Fut

Vector of futility boundaries.

nSims

Number of simulations to run for the phase 123 and conventional design.

References

[1] Chapple and Thall (2018).A Hybrid Phase I-II/III Clinical Trial Design Allowing Dose Re-Optimization in Phase III. Biometrics. In Press,

Examples

# NOT RUN {
 ##We need to specify Phase 12,
###Phase 3 trial paramters,
##the additional phase 123 parameters and simulation parameters
#This is scenario 3 for the exponetial case
##the additional phase 123 parameters and simulation parameters
###########PHASE12 Parameters ##################
DoseStart=1
##True Efficacy and Toxicity Probabilities
PT = c(.05,.08,.1,.15,.2)
PE=c(.2,.25,.35,.4,.55)
##Raw Dose Levels considered
Dose = c(1,2,3,3.5,5)
#Max Sample Size
NET=30
##Number of patients before randomization
NF=15
##Cohort size
cohort=3
##Hypermeans for Eff-Tox
Hypermeans = c(.022,3.45,0,-4.23,3.1,0)
Hypervars = c(2.6761, 2.6852, .2, 3.1304, 3.1165, 1)
Hypervars=Hypervars^2
##Contour Vector
Contour = c(.35, .75,.7,.4)
##Acceptability Criteria
PiLim = c(.3,.4)
ProbLim=c(.1,.1)
##Phase 12 accrual rate
Accrue12=5
###How long is the time window in phase 12?
Time12=1
##########PHASE3 Parameters####################
Nmax=500
##Number of patient events for interim looks
NLook = c(200,300,400)
##Superiority Boundaries
Sup = c(2.96, 2.53,1.99)
##Futility Boundaries (0 means no futility decision)
Fut = c(0,1.001,0)
##Average accrual rate for phase III
Accrue = 10
###########Phase123 Parameters###########
###Number of patient events to re-optimize doses
NLookSwitch=50
##Time in between phase 12 and phase 3
Twait=1
#########Simulation Parameters######
###Family of Distributions
Family="Gamma"
###Shape parameter, Not needed for Exponential
alpha=1
###True Beta vector (beta_1,exp(beta_E),-exp(beta_T),beta_2,beta_0)
betaA = c(.1, .3, -1,-1,3.6)
##True beta vector for (exp(beta_E),-exp(beta_T),beta_C)  of the control treatment
betaC=c(.3,-1,log(24/1.035111))
##True efficacy and toxicity probability for control group
ProbC = c(.3,.1)
##Number of simulations to run
nSims=1
##Run Simulations
Results=SimPhase123(DoseStart,Dose,PE,PT,Hypermeans,Hypervars,Contour,
                 PiLim,ProbLim,NET,NF,Accrue12,Time12,cohort,betaA,ProbC,betaC,
                Family,alpha,Nmax,Accrue,Twait,NLookSwitch,NLook,Sup,Fut,nSims)
# }