Current Sample Size Re-Estimation Methods for Censored Survival Data in Light of Noninferiority Studies

• Activity Number: 616
• Type: Contributed
• Date/Time: Wednesday, August 12, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Hwasoon Kim* and Jeff Szychowski
• Companies: and The University of Alabama at Birmingham
• Keywords: non-inferiority trial ; sample size re-estimation ; censored outcome ; power

Abstract

Study designs that allow sample size review may potentially save a study by identifying misspecified assumptions, modifying the planned sample size, and reinforcing the study's power. Most sample size re-estimation methods in non-inferiority trials have been developed for continuous or binary outcomes. In many medical domains studying cancer, heart failure, and other chronic diseases, most phase III trials use censored endpoints (e.g. survival or event-free survival). We review four different methods for the re-evaluation of sample size in superiority designs with censored outcomes and extend them to the context of non-inferiority designs with censored outcomes. Non-inferiority designs have inherent complexity by the introduction of the non-inferiority margin and therefore understanding of strategies in these methods is essential. We detail the differences and similarities between the methods through simulation studies in terms of type I error rate control, power, and additional sample size to be recruited. We also provide practical guide for application of sample size re-estimation in non-inferiority trials using an actual clinical trial as an example.