simtrials.surv {stoppingrule}

Simulate trials with safety monitoring by survival data stopping rules

Description

Internal workhorse function used to simulate trials with safety monitoring by survival data stopping rules. The provided stopping rule is used for monitoring of MC simulated trials. For each trial, a random sample is generated from a Weibull distribution with shape parameter s to attain a toxicity rate of p. Enrollment times are simulated over an accrual period of duration A under a uniform (0,A) distribution.

Usage

simtrials.surv(rule, p, MC, A, s = 1)

Arguments

rule

A rule.surv object with the safety stopping rule for evaluation

p

The probability of a toxicity occurring in tau units of time under the null hypothesis

MC

Number of Monte Carlo replicated datasets to simulate

A

Length of accrual period

s

Shape parameter for the Weibull distribution; default value is 1 (exponential distribution)

Value

A matrix with MC rows and 14 columns, one row per simulated trial. Columns include the stopping rule type and design parameters, the numbers of events and enrolled patients, the total follow-up time in the cohort, the calendar time when the study ends, the reject/no reject decision, and the last stage of monitoring reached when the study ends.

Examples

set.seed(13)
wt_rule = calc.rule.surv(n=46,p0=0.15,alpha=0.10,type="WT",tau=100,param=0.25)
sims = simtrials.surv(rule=wt_rule,p=0.15,MC=1000,A=1095)
c(mean(sims$stopped),mean(sims$n.Toxicity),mean(sims$n.Enrolled),mean(sims$Calendar.Time))
sims = simtrials.surv(rule=wt_rule,p=0.35,MC=1000,A=1095)
c(mean(sims$stopped),mean(sims$n.Toxicity),mean(sims$n.Enrolled),mean(sims$Calendar.Time))

gp_rule = calc.rule.surv(n=46,p0=0.15,alpha=0.10,type="GP",tau=100,param=11.5*c(-log(1-0.15),100))
sims = simtrials.surv(rule=gp_rule,p=0.15,MC=1000,A=1095)
c(mean(sims$stopped),mean(sims$n.Toxicity),mean(sims$n.Enrolled),mean(sims$Calendar.Time))
sims = simtrials.surv(rule=gp_rule,p=0.35,MC=1000,A=1095)
c(mean(sims$stopped),mean(sims$n.Toxicity),mean(sims$n.Enrolled),mean(sims$Calendar.Time))