A Seamless Adaptive 2-in-1 Design Expanding a Phase 2 Trial for Treatment or Dose Selection Into a Phase 3 Trial

Abstract

Seamless adaptive phase 2-3 designs provide possible pathways to expedite drug developments by allowing the expansion of an ongoing Phase 2 trial into a confirmatory Phase 3 trial. Here, we propose an adaptive 2-in-1 design which can expand an ongoing Phase 2 trial with multiple treatment or dose arms into a confirmatory Phase 3 trial with the selected arms based on intermediate endpoints from interim data for adaptive decision. The proposed adaptive design provides an efficient way to combine the treatment or dose selection stage and the confirmatory stage. We prove that the proposed design can preserve the familywise Type I error under a mild assumption that is expected to hold with practical considerations. Simulations are conducted to confirm the control of the familywise Type I error with an illustrated example design.