Sample size reestimation: A review and recommendations

Despite best efforts, some crucial information used to design a confirmatory trial may not be available, or may be available but with a high degree of uncertainty, at the design stage. When this happens, it may be prudent to check the validity of those assumptions using interim data from the study and make midcourse adjustment if necessary. One such adjustment is to modify the sample size. In this article, we focus on sample size reestimation (SSR) for phase III and IV studies. The discussion is relevant to both continuous and binary endpoints even though the basis for SSR might differ for those two cases. We review commonly used approaches to adjust sample size and provide recommendations on how SSR should be implemented to achieve the objectives and maintain the integrity of the trial. The recommendations cover scientific, procedural, and logistic considerations.