A menu-driven facility for sample-size calculation in novel multiarm, multistage randomized controlled trials with a time-to-event outcome
The features supported include unequal patient allocation, target hazard ratios that may differ from 1 under the null hypothesis, and the ability to stop patient recruitment at a specified time after trial initiation. The computations of sample size and power are based on the asymptotic mean and variance of the log hazard-ratio under the null and alternative hypotheses. The overall operating characteristics are computed from the intermediate and final stage significance levels and power, and the correlation between the log hazard-ratios on the intermediate and primary outcome measures at the different stages. We illustrate the approach with the design of a United Kingdom Medical Research Council six-arm trial in prostate cancer in which the intermediate outcome is failure-free survival and the primary outcome is overall survival. View all articles by these authors: Friederike M.-S. Barthel, Patrick Royston, Mahesh K. B. Parmar View all articles with these keywords: nstage, nstagemenu, multiple arms, randomized controlled trial, survival analysis, surrogate marker, multistage trial Download citation: BibTeX RISDownload citation and abstract: BibTeX RIS |