35: Evaluating Various Futility Options in Phase III Biomarker-Driven Trial Designs

Music City Center 

Phase III trials are essential for confirming efficacy and safety of new treatments but demand substantial time and resources. To improve efficiency, futility analysis is often conducted to stop trials early when success is unlikely. Our research focused on trials with biomarker (Bm) subgroup nested within Intent-to-treat (ITT) population and examined various futility designs: traditional, sequential (futility analysis performed on ITT first then Bm positive) and parallel (futility analysis performed on Bm positive and negative subgroups simultaneously). Using extensive simulations, we evaluated type I error, power, futility rates, average sample size and average trial duration. Results showed that sequential method, while not inflating type I error rate, exhibited a considerable low futility rate under the null, leading to higher average sample sizes and longer trial durations. In contrast, parallel futility design provided a higher futility rate under the null, lower average sample sizes, shorter trial durations while maintaining an effective type I error control and a reasonable power reduction, making it a more suitable approach for Phase III trials with Bm-defined subgroups.

Phase III clinical trial

Futility analysis

Key Operating Characteristics 

Biopharmaceutical Section