PS39:Contributions of Phases: Statistical Considerations in Study Designs and Regulatory Perspectives

Drug development sometimes requires evaluating investigational products across multiple phases of disease treatment. For example, whether maintenance treatment is needed after induction therapy, or whether treatment is needed in the post-surgery phase. In a public workshop co-sponsored by FDA and AACR in May 2024, challenges associated with multi-phase trial designs were highlighted, particularly the difficulty in isolating the contribution of each phase of treatment to the effect of the overall regimen. This importance of isolating the contribution of each phase was further underscored during the ODAC meeting in July 2024, where the AEGEAN trial of a perioperative regimen for resectable non-small cell lung cancer was discussed. Questions were raised regarding the limitations of the existing design to isolate the contribution of the post-surgery treatment phase specifically. Building on these discussions, this session brings together speakers and panelists who were part of AEGEAN ODAC and the FDA/AACR workshop to examine statistical and regulatory considerations in study designs for multi-phase treatments. Topics will include design options for multi-phase treatments and the implications for sample size, power, study duration, and potential multiplicity considerations, as well as expectations for formal comparisons to establish individual phase contributions. The session will also explore the advantages and potential practical challenges of employing SMART designs. Perspectives on isolating the treatment effect of each phase for different diseases such as hematology and solid tumors, as well as indications outside of oncology such as Crohn's Disease and Ulcerative Colitis with considerations from different phases of interest will be elaborated. The session will feature presentations from industry and regulatory representatives, followed by a focused panel discussion with statisticians from FDA and industry and a clinical reviewer from FDA to synthesize insights and address practical challenges.