Clarifying clinical trial aims and analysis using the estimands framework

ViCBiostat Summer School 2021, proudly supported by ACTA

Clinical studies aim to quantify the treatment effect associated with the primary study question. Estimating this treatment effect in a randomised controlled trial can be challenging in the presence of post-randomisation events such as use of rescue medication or stopping, switching between treatment arms, or missing data. These issues may lead to difficulties in the interpretation of the treatment effect estimate and affect the validity of the study findings. The estimands framework, presented in the International Council for HarmonisationE9 (R1) Addendum, bridges the gap between the study objectives and the statistical analysis. It adds clarity to trial objectives, informs the study design and data collection, and determines the choice of statistical analysis methods. This half-day workshop will cover why, how, who and when to define and document estimands based on internationally agreed guidelines. It is designed for participants with some knowledge of implementing a clinical trial within any discipline. Participants will workshop estimands within cross-disciplinary breakout groups.


Trials with similar, or even identical, objectives can produce highly variable reports of treatment effect. Whilst some of this variability can be attributed to chance, other factors, such as eligibility for the analytic population, correction for post-randomisation events (e.g., use of rescue medication, stopping or switching treatment), adjustment for missing data and choice of statistical analysis, need greater clarity to ensure that the reported treatment effect is not misunderstood. Estimands provide a framework to incorporate these factors at the trial’s design stage by linking the treatment effect of greatest relevance to regulatory and clinical decision making to the trial’s objective.


This half-day workshop will cover why, how, who and when to define and document trial estimands based on internationally agreed guidelines. It is designed for participants with some knowledge of implementing a clinical trial within any discipline. Participants will workshop estimands within cross-disciplinary breakout groups.