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Aligning Estimators With Estimands in Clinical Trials: Putting the ICH E9(R1) Guidelines Into Practice

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The draft ICH E9(R1) addendum stipulates that an estimator should align with its associated estimand and yield an estimate that facilitates reliable interpretations. The addendum further stipulates that assumptions should be justifiable and plausible, and that the extent of assumptions is an important consideration for whether an estimate will be robust because assumptions are often unverifiable. The draft addendum specifies 5 strategies for dealing with intercurrent events. The intent of this paper is to provide conceptual considerations and technical details for various estimators that align with these strategies. We include focus on how the nature and extent of assumptions influences the potential robustness of the various estimators. The content reflects the knowledge, experience, and opinions of the Drug Information Association’s Scientific Working Group on Missing Data. This group includes experienced statisticians from across industry and academia, primarily in the US and European Union.

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Correspondence to M. O’Kelly PhD.

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Mallinckrodt, C.H., Bell, J., Liu, G. et al. Aligning Estimators With Estimands in Clinical Trials: Putting the ICH E9(R1) Guidelines Into Practice. Ther Innov Regul Sci 54, 353–364 (2020).

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