sim.trial.2 {SAME}

Function to simulate Bayesian seamless multi-arm biomarker-enriched phase II/III designs with user-defined cutoff points

Description

This function finds the required number of events using a multi-arm multi-stage biomarker-enriched design with time-to-event endpoints with the user-defined cutoff points.

Usage

sim.trial.2(
  median.c,
  hr,
  K,
  L,
  lfu,
  alpha,
  power,
  accrate,
  theta,
  bio.preva,
  FAtime.phase3,
  eta,
  futility,
  superiority,
  N.iter
)

Arguments

median.c

The median survival time for control group

hr

Alternative hazard ratio

K

Number of biomarkers

L

Information fraction in terms of the accumulative events in phase II stage, e.g., K = c(1/4,1/2,1)

lfu

Follow-up time

alpha

One-sided family-wise error rate

power

Power

accrate

Accrual rate

theta

A clinically meaningful treatment effect size defined by clinicians

bio.preva

Prevalence of biomarker(s)

FAtime.phase3

the study ending time of phase III

eta

A cutoff probability for the strength of evidence for decision-making and defined by user.

futility

cutoff point for futility termination

superiority

cutoff point for superiority termination

N.iter

Number of iterations

Value

sim.trial.2() returns the nominal type I error rate, nominal power under user-defined hypothesis, empirical power under user-defined number of simulations, the duration of trial(time), the number of events (num_evs), the number of patients (num_pts) from different stages. The function can also display the number of events and patients under the selected subgroup, the distribution of decision zones and the estimated hazard ratio for the final analysis.

Examples

 sim.trial.2(median.c=12,hr=c(1,1,1,0.6),K=2,L=c(1/4,1/2,1),lfu=0,alpha=0.05,
             power=0.9,accrate=15,theta=log(1.25),bio.preva=c(0.4,0.6),
             FAtime.phase3=48,eta=0.2,futility=0.1,superiority=0.9,
             N.iter=3)