International – ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials

To properly inform decision making by pharmaceutical companies, regulators, patients, physicians and other stakeholders, clear descriptions of the benefits and risks of a treatment (medicine) for a given medical condition should be made available. Without such clarity, there is a concern that the reported “treatment effect” will be misunderstood. This addendum presents a structured framework to strengthen the dialogue between disciplines involved in the formulation of clinical trial objectives, design, conduct, analysis and interpretation, as well as between sponsor and regulator regarding the treatment effect(s) of interest that a clinical trial should address.

Precision in describing a treatment effect of interest is facilitated by constructing the “estimand” (see Glossary; A.3.) corresponding to a clinical question of interest. Clarity requires a thoughtful envisioning of “intercurrent events” (see Glossary; A.3.1.) such as discontinuation of assigned treatment, use of an additional or alternative treatment and terminal events such as death. The description of an estimand should reflect the clinical question of interest in respect of these intercurrent events, and this addendum introduces strategies to reflect different questions of interest that might be posed. The choice of strategies can influence how more conventional attributes of a trial are reflected when
describing the clinical question, for example the treatments, population or the variable (endpoint) of interest…