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An addendum of the ICH E9 guideline on Statistical Principles for Clinical Trials was released in November 2019 introducing estimand framework. The framework aims to align trial objectives and statistical analyses by requiring a precise definition of the treatment effect of interest. This definition accounts for intercurrent events such as switching to new anticancer therapies for the analysis of the overall survival (OS), the gold standard in oncology.
Traditional OS analysis in confirmatory studies uses intention-to-treat (ITT) approach comparing treatments as they were initially randomized regardless of whether treatment switching occurred (treatment-policy strategy). Regulatory authorities and other stakeholders often consider ITT results as most relevant. However, the respective estimand only yields a clinically meaningful comparison of two treatment arms if subsequent therapies are already approved and reflect clinical practice. We illustrate different scenarios where subsequent therapies are not yet approved drugs and thus do not reflect clinical practice. In such situations hypothetical strategy could be more meaningful from patient’s and prescriber’s perspective.
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