Kelly Van Lancker, Ghent University.

• Title: Potential estimands and estimators for clinical trials impacted by COVID-19

• Abstract: The COVID-19 pandemic continues to affect the conduct of clinical trials of medical products globally. Complications may arise from pandemic-related operational challenges such as site closure, travel limitations and interruptions to the supply chain for the investigational product, or from health-related challenges such as COVID-19 infected trial participants. Some of these complications lead to unforeseen intercurrent events in the sense that they affect either the interpretation or the existence of the measurements associated with the clinical question of interest. The ICH E9(R1) Addendum on estimands provides a rigorous basis to discuss potential pandemic-related trial disruptions and embed them in the context of study objectives and design elements. In this talk, we focus on the use of the hypothetical strategy and to a lesser extent the treatment-policy strategy to frame clinical questions in the presence of the unforeseen intercurrent events due to the COVID-19 pandemic. It should be noted that different hypothetical strategies could be considered and care has to be taken that the envisaged scenario, in which the intercurrent event would not occur, is precisely described. For their estimation, we will consider different causal inference and missing data methods such as multiple imputation and (augmented) inverse probability weighting. To clarify, we describe the features of a stylized trial in neuroscience, and how it may have been impacted by the pandemic. This stylized trial will then be re-visited by discussing the changes to the estimand and the estimator to account for pandemic disruptions.