Enhancing Estimand Related Sponsor-regulatory Interactions

The estimand framework has become an integral component of trial planning, being routinely applied in Phase 3 protocols and used in sponsor-regulatory interactions. This session will discuss ways in which the estimand framework can be applied successfully in sponsor-regulatory interactions, regulatory decision-making, and eventually, labelling when providing prescribers and patients with relevant, regulated information. Three presentations will set-up the stage for the panel discussion. First presentation will review how the upcoming ICH M11 protocol template plans to incorporate the estimand framework from defining trial objectives, estimands, and their rationale to analysis sections that are aligned with each defined objective. The presenter will highlight how this template will facilitate the application of the estimand framework and the sponsor-regulatory interactions. Second presentation will highlight a case study in which the application of the estimand framework was applied from start (documentation in the protocol) through to reporting results in the study report and finally in communication of the treatment effects in the label and primary manuscript. The presenter will comment on some of the regulatory interactions with respect to estimands and alignment with estimation methods and will discuss some of the challenges that the team faced with regards to ensuring clear communication of results (in light of estimands) in the public domain. Key learnings for the future will be provided. Third presentation will highlight how the estimand framework was incorporated in label discussions in case studies at FDA. A panel discussion will follow, with the speakers and two additional panelists from FDA and pharmaceutical industry. The panelists will further expand the ideas from presentations, touching upon how estimand related sponsor-regulatory interactions can be enriched from protocol documentation to discussion of trial results and documentation in the label. Directions in the which the application of the estimand framework can evolve in the future will also be highlighted.