A Critical Review on Adaptive Sample Size Re-estimation (SSR) Designs for Superiority Trials with Continuous Endpoints

Abstract

Adaptive sample size re-estimation (SSR) methods have been widely used for designing clinical trials, especially during the past two decades. We give a critical review for several commonly used two-stage adaptive SSR designs for superiority trials with continuous endpoints. The objective, design and some of our suggestions and concerns of each design will be discussed in this paper. Keywords: Adaptive Design; Sample Size Re-estimation; Review Introduction Sample size determination is a key part of designing clinical trials. The objective of a good clinical trial design is to achieve the balance between efficiently spending resources and enrolling enough patients to achieve a desired power. At the designing stage of a clinical trial, there usually only have limited information available about the population, so that the sample size calculated at this stage may not be sufficient to address the study objective. Assumed that the data from two parallel treatment groups (e.g. treatment and control groups) are normally distributed with mean treatment effect μ_1 and μ_2, and equal within-group variance 𝜎2. Let the mean difference (treatment effect) . The efficacy of the treatment will be evaluated by testing the hypothesis.