Defining estimands in clinical trials: A unified procedure

The ICH E9 (R1) addendum proposes five strategies to define estimands by addressing intercurrent events. However, mathematical forms of these targeted quantities are lacking, which might lead to discordance between statisticians who estimate these quantities and clinicians, drug sponsors, and regula...

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Bibliographic Details
Published in:Statistics in medicine 2023-05, Vol.42 (12), p.1869-1887
Main Authors: Han, Shasha, Zhou, Xiao‐Hua
Format: Article
Language:English
Subjects:
causal inference
clinical trials
Data Collection
Data Interpretation, Statistical
estimands
Humans
intercurrent events
Models, Statistical
post‐treatment variables
Research Design
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Summary:The ICH E9 (R1) addendum proposes five strategies to define estimands by addressing intercurrent events. However, mathematical forms of these targeted quantities are lacking, which might lead to discordance between statisticians who estimate these quantities and clinicians, drug sponsors, and regulators who interpret them. To improve the concordance, we provide a unified four‐step procedure for constructing the mathematical estimands. We apply the procedure for each strategy to derive the mathematical estimands and compare the five strategies in practical interpretations, data collection, and analytical methods. Finally, we show that the procedure can help ease tasks of defining estimands in settings with multiple types of intercurrent events using two real clinical trials.
ISSN:0277-6715
1097-0258
DOI:10.1002/sim.9702