An adaptive seamless Phase 2-3 design with multiple endpoints

Area of Science:

• Clinical trial design
• Biostatistics
• Drug development

Background:

• Expediting drug development is crucial for timely patient access to new therapies.
• Adaptive seamless Phase 2-3 designs offer a pathway to accelerate clinical trials.
• Managing multiple endpoints in drug approval processes presents statistical challenges.

Purpose of the Study:

• To propose an adaptive seamless Phase 2-3 design incorporating multiple endpoints.
• To enable expansion from an ongoing Phase 2 trial to a Phase 3 trial based on intermediate results.
• To ensure robust statistical testing of multiple endpoints while controlling Type I error.

Main Methods:

• Development of an adaptive seamless Phase 2-3 design.
• Integration of an intermediate endpoint for adaptive decision-making.
• Application of a powerful multiple test procedure for multiple endpoints.
• Statistical proof of familywise Type I error control under practical assumptions.

Main Results:

• The proposed design effectively expands Phase 2 trials into Phase 3.
• The multiple test procedure maintains statistical power for multiple endpoints.
• Familywise Type I error is preserved under mild assumptions.
• Simulations confirm the design's statistical validity and error control.

Conclusions:

• The adaptive seamless Phase 2-3 design is a viable strategy for efficient drug development.
• This approach facilitates the testing of multiple endpoints in oncology and other fields.
• The design offers a statistically sound method for accelerating regulatory approval pathways.