The session will bring FDA and Industry Clinicians and Statisticians who have worked on the series on Getting the Questions Right or GTQR based upon applying ICH E9 (R1) to design clinical trials with clinically meaningful endpoints acceptable to regulatory authorities. Most organizations rely on their statisticians to use the “best approaches”. A randomized, double blind, placebo-controlled study is accepted as the gold standard. Randomization does not protect from bias due to events that occur after randomization, e.g. death, discontinuation of treatment, treatment switching, taking rescue medication or missing data due to various reasons. At present, these post-randomization events are dealt with implicitly based on choices made about the data collection and statistical analysis.
Analysis specifications related to key endpoints that were not pre-specified in the protocol are looked at with suspicion by regulators. In order to have greater transparency and clarity from regulators, the Draft ICH E9 (R1) Addendum “Statistical Principles for Clinical Trials: Estimands and Sensitivity Analysis in Clinical Trials”, was issued in June 2017..
An estimand includes (a) the patient population targeted by the scientific question (b) the variable (or endpoint), to be obtained for each patient, that is required to address the scientific question (c) the specification of how to account for intercurrent events to reflect the scientific question of interest (d) the population-level summary (e.g. means) for the variable which provides, as required, a basis for a comparison between treatment conditions.
The GTQR series conducted as 6 Webinars in 2018 brought together multiple stakeholders to advance the understanding and implementation of Estimands. This session will share key learnings that attendees can apply to improve the design and analysis of clinical trials.