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Abstract:
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The ICH E9 Addendum introduces various strategies for addressing intercurrent events when defining the clinical question of interest. For hypothetical estimand strategies a scenario is envisaged in which the intercurrent event would not occur: the value which the variable would have taken in the hypothetical scenario defined. If a hypothetical strategy is proposed, it should be made clear what hypothetical scenario is envisaged. For example, wording such as 'if the patient does not take additional medication' might lead to confusion as to whether the patient hypothetically does not take additional medication because it is not available or because the particular patient is supposed not to require it. The E9 Addendum acknowledges that a wide variety of hypothetical scenarios can be envisaged, but it also clarifies that some scenarios are likely to be of more clinical or regulatory interest than others. While the Addendum gives several example scenarios, the debate on the role of hypothetical estimand strategies in clinical trials continues. In this presentation we share our experiences and try to provide a scientific rationale to differentiate between 'good' and 'bad' hypotheticals.
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