Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test

Stat Med. 2014 May 30;33(12):2004-16. doi: 10.1002/sim.6073. Epub 2013 Dec 13.


Phase II clinical trials are often conducted to determine whether a new treatment is sufficiently promising to warrant a major controlled clinical evaluation against a standard therapy. We consider single-arm phase II clinical trials with right censored survival time responses where the ordinary one-sample logrank test is commonly used for testing the treatment efficacy. For planning such clinical trials, this paper presents two-stage designs that are optimal in the sense that the expected sample size is minimized if the new regimen has low efficacy subject to constraints of the type I and type II errors. Two-stage designs, which minimize the maximal sample size, are also determined. Optimal and minimax designs for a range of design parameters are tabulated along with examples.

Keywords: logrank test; minimax design; optimal design; single arm trial; time to event; two-stage design.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Clinical Trials, Phase II as Topic / statistics & numerical data
  • Data Interpretation, Statistical
  • Disease-Free Survival*
  • Humans
  • Research Design*
  • Sample Size
  • Treatment Outcome