Current Practice on Multiplicity Adjustment and Sample Size Calculation in Multi-arm Clinical Trials: An Industry Survey in Japan.

Abstract

This study provides the results of a survey on the current practice of multiplicity adjustment and sample size calculation in multi-arm clinical trials. The survey was aimed at members of the Japan Pharmaceutical Manufacturers Association (JPMA) and was conducted in 2015. Of the 66 JPMA member companies, effective responses were obtained on 151 trials from 33 companies based in Japan and 11 companies based in other countries. The results from this survey indicate that multiplicity adjustment in confirmatory multi-arm trials is adequate in terms of controlling the familywise error rate. Multiplicity was adjusted in 38.3% of exploratory multi-arm trials. Various multiple comparison procedures (MCPs) were applied, with the fixed sequence procedure being the one applied most frequently. This survey also reveals that there are issues that need to be addressed within sample size calculation. To adequately design a multi-arm clinical trial, it is important within sample size calculation to consider whether to perform multiplicity adjustment, select MCPs, and define their power.