Sample Size Re-estimation Designs In Confirmatory Clinical Trials—Current State, Statistical Considerations, and Practical Guidance

A sample size re-estimation (SSR) design is a flexible, adaptive design with the primary purpose of allowing sample size of a study to be reassessed in the mid-course of the study to ensure adequate power. In real world drug product, biologic, and device development, there may be large uncertainty in key factors that drive the sample size estimation for a confirmatory clinical trial. For example, early phase studies may have encouraging results but could be of shorter duration, or use a different endpoint than what is required for confirmatory phase clinical trials. The negative impact of high uncertainty at design stage for a confirmatory trial can be mitigated by an SSR design. Recent surveys have reported an encouraging upward trend in the use of SSR designs in clinical trials since the release of the draft guidance for adaptive design clinical trials for drugs and biologics by the U.S. Food and Drug Administration in 2010 (U.S. Food and Drug Administration (FDA) (February, 2010), Draft Guidance for In...