Keywords: estimand, estimator, ICH E9(R1), sensitivity analysis
Draft ICH E9(R1) Addendum on “Estimand and Sensitivity Analysis in Clinical Trials” provides different strategies for addressing intercurrent events in defining the estimand and describing the treatment effect that is targeted. Clinical trials are often faced with more than one intercurrent event and the set of intercurrent events for consideration will depend on the specific therapeutic setting and trial objectives. We will consider a case study of a trial investigating treatment effect of a new drug in subjects who are asymptomatic at risk for developing Alzheimer’s dementia to illustrate the definition of different estimands which correspond to different scientific questions of interest. The potential intercurrent events will be identified. We will show how the selection of various strategies for intercurrent events translates into different estimators and what kind of sensitivity analyses could be considered to explore the robustness of inferences from the main estimator to deviations from its underlying modelling assumptions and limitations in the data. Points will be highlighted on how statisticians could broaden the current practice to address the challenges of complex estimands.