Exact two-stage designs for phase II activity trials with rank-based endpoints

Contemp Clin Trials. 2012 Mar;33(2):332-41. doi: 10.1016/j.cct.2011.10.008. Epub 2011 Oct 30.


Features common to phase II clinical trials include limited knowledge of the experimental treatment being evaluated, design components reflecting ethical considerations, and small to moderate sample sizes as a result of resource constraints. It is for these reasons that there exist many two-stage designs proposed in the literature for use in this context. The majority of these designs are for binary endpoints and based on exact probability calculations, or are for continuous endpoints and rooted in asymptotic approximations to the null distribution. We present exact two-stage Mann-Whitney designs in the context of two-arm randomized clinical trials. In addition to describing the designs, we present tables of decision rules under a variety of assumed realities for use in trial planning.

MeSH terms

  • Clinical Trials, Phase II as Topic / methods*
  • Endpoint Determination / methods*
  • Humans
  • Models, Theoretical*
  • Research Design*
  • Sample Size