The CRT-Estimands Framework
The CRT-Estimands Framework is a consensus-based extension of the ICH E9(R1) estimands framework developed specifically for cluster randomised trials. It identifies five attributes that must be described when defining an estimand in a cluster randomised trial, and was developed through a structured consensus process involving a scoping review, an international Delphi study, and a meeting of international experts.
Introduction and motivation
The International Conference on Harmonisation (ICH) released the ICH E9(R1) Addendum On Estimands and Sensitivity Analyses in Clinical Trials in 2020 which set out a framework for defining estimands – a precise description of the treatment effect to be estimated in a trial.[1] However, the ICH E9(R1) addendum was primarily developed with individually randomised trials in mind, and since its publication there has been emerging evidence that cluster randomised trials (CRTs) have additional challenges for defining estimands.
In response to this, the CRT-Estimands Framework was developed.[2] It is a consensus-based extension of the ICH E9(R1) framework for cluster randomised trials. It lists 5 attributes that need to be described when defining estimands for cluster randomised trials.
Development process
The framework was developed using standard consensus methods, including: (i) a scoping review;[3] (ii) an international Delphi study;[4] (iii) and a consensus meeting of international experts.[2]
The CRT-estimands framework
The CRT-Estimands Framework provides 5 attributes that should be described when defining estimands in cluster randomised trials:
- Population of individuals and clusters
- Treatment conditions
- Endpoint/outcome variable
- Strategies to handle individual and cluster level intercurrent events
- Population-level summary measure, including how individuals and clusters are weighted (e.g. individual-average), and whether summaries are marginal or cluster-specific, if applicable
References
- ↑ "ICH E9(R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials" (PDF). International Council for Harmonisation.
- 1 2 Kahan, BC; Bretz, F; Copas, A; et al. (2026). "CRT-Estimands Framework: consensus based extension of the ICH E9(R1) addendum for cluster randomised trials". BMJ. 393 e089050. doi:10.1136/bmj-2025-089050.
- ↑ Bi, Dongquan; Copas, Andrew; Kahan, Brennan. "A scoping review identified additional considerations for defining estimands in cluster randomised trials". Journal of Clinical Epidemiology.
- ↑ Kahan, Brennan C; Bahti, Melanie; Bi, Dongquan; Bretz, Frank; Collins, Gary S; Copas, Andrew; Harhay, Michael O; Fan, Li; Catherine, Auriemma. "Development of a consensus extension of the estimands framework for cluster randomised trials (CRT-estimands): results from an international Delphi study". Trials. 10 (1): 70.