Speaker
Description
Reliable estimation of treatment effects is essential for the benefit–risk assessment supporting the approval of new drugs and for the communication of trial results in the European Public Assessment Report (EPAR) and Summary of Product Characteristics (SmPC). In adaptive designs, where trial adaptations such as sample size re-assessment, population enrichment, or treatment arm selection are implemented, estimation becomes particularly challenging. These adaptations may introduce complexities in the estimation of treatment effects, both in terms of bias and precision, but also in the definition of what effect is being estimated—especially when design modifications alter the target population or other components of the estimand.
This presentation will summarise the current regulatory guidance relevant to estimation following adaptive designs, including the EMA Reflection Paper on Methodological Issues in Confirmatory Clinical Trials Planned with an Adaptive Design, the draft ICH E20 Guideline on Adaptive Clinical Trials (EMA/CHMP/ICH/82035/2023, draft 2023), and related guidance. These documents highlight the importance of pre-specifying estimands, maintaining interpretability of estimates, and ensuring transparency about the impact of adaptations on estimation and inference.
Examples from recent regulatory procedures will illustrate how estimation issues were addressed in practice, including the communication of treatment effects in the EPAR and SmPC. The presentation will also discuss areas where methodological developments and harmonised regulatory expectations are still needed to support the use of adaptive designs for confirmatory evidence generation.
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