A gated group sequential design for seamless Phase II/III trial with subpopulation selection

BMC Medical Research Methodology

Research

Keaven Anderson¹  Jing Yang¹  Jason J. Z. Liao²  Guanhong Miao³ 

[1] BARDS, Merck & Co., Inc, 19454, North Wales, PA, USA;Biostatistics, Incyte Corporation, 19803, Willington, DE, USA;Department of Biostatistics, University of Florida, 32611, Gainesville, FL, USA;

关键词: Gated group sequential design;    Seamless Phase II/III;    Subpopulation selection;    Power;    Type I error;   

DOI  :  10.1186/s12874-022-01825-0

 received in 2022-07-15, accepted in 2022-12-19,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDue to the high cost and high failure rate of Phase III trials where a classical group sequential design (GSD) is usually used, seamless Phase II/III designs are more and more popular to improve trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior to committing to the full cost of a Phase III trial. Population selection during the trial allows a trial to adapt and focus investment where it is most likely to provide patient benefit. Previous methods have been developed for this problem when there is a single primary endpoint and two possible populations.MethodsTo find the population that potentially benefits with one or two primary endpoints (e.g., progression free survival (PFS), overall survival (OS)), we propose a gated group sequential design for a seamless Phase II/III trial design with adaptive population selection.ResultsThe investigated design controls the familywise error rate and allows multiple interim analyses to enable early stopping for efficacy or futility. Simulations and an illustrative example suggest that the proposed gated group sequential design has more power and requires less time and resources compared to the group sequential design and adaptive design.ConclusionsCombining the group sequential design and adaptive design, the gated group sequential design has more power and higher efficiency while controlling for the familywise error rate. It has the potential to save drug development cost and more quickly fulfill unmet medical needs.

【 授权许可】

CC BY   
© The Author(s) 2022

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