The estimand framework requires a precise definition of the treatment effect (“estimand”) as different ways of accounting for “intercurrent” events post randomization may result in different scientific questions.
The initiation of alternative therapy is common in oncology clinical trials. Two possible ways to account for this intercurrent event are to censor at initiation or to consider the start of therapy as an event. The new framework clarifies that these address different questions (“does the drug delay relapse if no patient had received new therapy” vs “does the drug delay relapse or start of new therapy”). The estimand framework facilitates discussions during clinical trial design to ensure alignment between the key question of interest, the analysis, and interpretation.
This presentation is a result of a cross-industry collaboration to connect the ICH E9 addendum concepts to applications. Data from previously reported randomized phase 3 studies will be used to consider common intercurrent events in solid tumor studies, to illustrate different scientific questions and the consequences of the estimand choice for study design, data collection, analysis, and interpretation.