CRT-Estimands Framework: Consensus based extension of the ICH E9(R1) addendum for cluster randomised trials

In order to assess the relevance of trial results or the appropriate trials methods, interest holders (eg, clinicians, patients, and policy makers) need a clear description of the trial’s research question. To improve clarity and consistency in clinical trials, the International Conference on Harmonisation (ICH) released the ICH E9(R1) addendum, which set out a framework for defining estimands—a precise description of the treatment effect to be estimated. While the ICH E9(R1) addendum has been widely adopted, it primarily focused on individually randomised trials. In contrast, cluster randomised trials, where groups of individuals are randomised, present additional challenges for defining estimands. Therefore, the CRT-Estimands Framework was developed as a consensus based extension of the ICH E9(R1) addendum for cluster randomised trials. This framework provides a set of attributes that should be described when defining estimands in cluster randomised trials, with the objective of improving the clarity of the estimands, and consequently, the research questions, in these trials. This article presents the CRT-Estimands Framework with explanations and examples of how it can be implemented. Adopting the framework will improve the clarity of estimands in cluster randomised trials and facilitate interest holders to make informed decisions from these trials.

Brennan C Kahan, Frank Bretz, Andrew Copas, Michael O Harhay, Gary S Collins, Melanie Bahti, Dongquan Bi, Marion K Campbell, Katherine R Courtright, Timothy Feeney, Andrew B Forbes, Amit X Garg, Scott D Halpern, Patrick J Heagerty, Karla Hemming, Sally Hopewell, James P Hughes, David M Murray, Joseph S Ross, Derek Stewart, Monica Taljaard, Obioha C Ukoumunne, Catherine L Auriemma, Fan Li