Sample size calculation based on efficient unconditional tests for clinical trials with historical controls

J Biopharm Stat. 2016;26(2):240-9. doi: 10.1080/10543406.2014.1000545. Epub 2014 Dec 31.


In historical clinical trials, the sample size and the number of success in the control group are often considered as given. The traditional method for sample size calculation is based on an asymptotic approach developed by Makuch and Simon (1980). Exact unconditional approaches may be considered as alternative to control for the type I error rate where the asymptotic approach may fail to do so. We provide the sample size calculation using an efficient exact unconditional testing procedure based on estimation and maximization. The sample size using the exact unconditional approach based on estimation and maximization is generally smaller than those based on the other approaches.

Keywords: E+M approach; Exact test; historical clinical trial; sample size; unconditional test.

MeSH terms

  • Algorithms
  • Confidence Intervals
  • Controlled Clinical Trials as Topic / methods
  • Controlled Clinical Trials as Topic / statistics & numerical data*
  • Data Interpretation, Statistical
  • Historically Controlled Study / methods
  • Historically Controlled Study / statistics & numerical data*
  • Humans
  • Models, Statistical*
  • Sample Size*
  • Treatment Outcome