All Times EDT
Keywords: estimands, principal stratum, sensitivity analyses, survival analysis, subgroups
In November 2014, the International Council on Harmonization (ICH) tasked an expert working group with development of an addendum to the ICH E9 guideline (Statistical Principles for Clinical Trials) to enable improved clarity in the description of benefits and risks of new treatments for given medical conditions. Five years later, the resulting ICH E9 (R1) guidance document began its journey of adoption by international regulatory authorities, including by the FDA in May 2021. In this presentation we will review how the framework on estimands and sensitivity analyses articulated in the addendum has impacted clinical development and associated methodological research thus far. In addition, we will discuss how alignment with ICH E9 (R1) can be strengthened in three areas for randomized clinical trials: (1) clinically interpretable estimand-aligned analyses for time-to-event endpoints, (2) applicability of the principal stratum strategy, and (3) the role of estimands and estimation in subgroup analyses. Examples across multiple therapeutic areas will be used to reinforce the key points.