Flexible seamless 2-in-1 design with sample size adaptation.

Area of Science:

• Clinical trial design
• Oncology drug development
• Biostatistics

Background:

• The 2-in-1 design offers flexibility in oncology trials using interim data for decisions.
• Current 2-in-1 designs are rigid, requiring a pre-specified fixed sample size.
• This rigidity limits adaptability in drug development timelines and resource allocation.

Purpose of the Study:

• To propose a flexible 2-in-1 clinical trial design with sample size adaptation.
• To retain the benefit of using intermediate endpoints for interim decision-making.
• To align with regulatory initiatives like FDA's Project FrontRunner for accelerated approval pathways.

Main Methods:

• Development of a novel 2-in-1 design incorporating sample size adaptation.
• Identification of an interim decision cut-off for conventional final analysis testing.
• Extensive simulation studies to evaluate design performance.

Main Results:

• The proposed flexible design requires a significantly smaller sample size.
• The adaptive design leads to a shorter overall trial timeline.
• Achieved similar statistical power compared to the simple 2-in-1 design.

Conclusions:

• The flexible 2-in-1 design offers a more efficient and adaptable approach to oncology drug development.
• This design supports regulatory goals for accelerated approval using surrogate endpoints.
• Demonstrated practical benefits through a multiple myeloma case study.