PS12: Evolving Use of the Estimand Framework in Regulatory Applications

The estimand framework has become an integral component of trial planning, routinely applied in Phase 3 protocols and widely used in sponsor-regulatory interactions. This session will explore how the application of the estimand framework can evolve to further enhance its utility in regulatory decision-making, sponsor-regulatory interactions and ultimately, through labeling documentation, providing prescribers and patients with relevant, regulated information. The session will open with a presentation delivered by a former member of the ICH E9(R1) Expert Working Group with extensive EU regulatory experience. Using practical examples, this presentation will emphasize the importance of framing clinical questions of interest that are relevant to trial stakeholders as the basis for meaningful discussions about treatment effects. This presentation promotes multi-disciplinary collaborations by shifting the focus from isolated estimand attributes, such as intercurrent events and their strategies, to a broader clinical context. The second presentation, also delivered by another former member of the ICH E9(R1) Expert Working Group, will build on the first by providing examples in which differing clinical questions might be relevant for regulatory decision making versus labeling. Following these presentations, a panel discussion will feature three senior members from FDA CDER, CBER and CDRH, all with deep expertise in the application of the estimand framework. The panelists will reflect on key issues using examples from the two presentations, offering insights into the evolving application of the estimand framework in clinical research. Topics to be addressed include: • The impact of the estimand framework on information presented in the label – current examples and potential future directions; • Principles for formulating clinical questions of interest, and when these might differ between regulatory decision making and labeling; • The trade-off between relevant clinical questions of interest and the reliability of analysis; • The role of the upcoming ICH M11 protocol template in facilitating sponsor-regulatory interactions; • Opportunities for future advancements in applying the estimand framework. The session will conclude with an interactive Q&A from the audience.