Application of sample size re-estimation in clinical trials: A systematic review

Abstract

Background: Sample size re-estimation (SSR) is a method used to recalculate sample size during clinical trial conduct to address a lack of adequate information and can have a significant impact on study size, duration, resources, and cost. Few studies to date have summarized the conditions and circumstances under which SSR is applied. We therefore performed a systematic review of the literature related to SSR to better understand its application in clinical trial settings. Methods: PubMed was used as the primary search source, supplemented with information from ClinicalTrials.gov where necessary details were lacking from PubMed. A systematic review was performed according to a pre-specified search strategy to identify clinical trials using SSR. Features of SSR, such as study phase and study start year, were summarized. Results: In total, 253 publications met the pre-specified search criteria and 27 clinical trials were subsequently determined as relevant in SSR usage. Among trials where the study phase was provided, 2 (7.4%) trials were Phase I, 5 (18.5%) trials were Phase II, 11 (40.7%) trials were Phase III, and 2 (7.4%) trials were Phase IV. Conclusion: Our results showed that SSR is also used in Phase I and II, which involve earlier decision making. We expect that SSR will continue to be used in early-phase trials where sufficient prior information may not be available. Furthermore, no major trends were observed in relation to therapy area or type of SSR, meaning that SSR may become a feasible and widely applied method in the future.

Keywords

• Adaptive design
• Clinical trial
• Sample size re-estimation
• Systematic review