SimPhase123 {Phase123} | R Documentation |
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)
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)
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. |
[1] Chapple and Thall (2018).A Hybrid Phase I-II/III Clinical Trial Design Allowing Dose Re-Optimization in Phase III. Biometrics. In Press,
##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)