CRT-Estimands Framework: consensus based extension of the ICH E9(R1) addendum for cluster randomised trials
Year: 2026
Type: article
Abstract: 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.
Source: BMJ
Authors: 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
Institutions: MRC Clinical Trials Unit at UCL, University College London, Novartis (Switzerland), Medical University of Vienna, University of Pennsylvania, University of Birmingham, University of Aberdeen, University of North Carolina at Chapel Hill, BMJ Group (United Kingdom), Monash University, Western University, University of Washington, University of Oxford, National Institutes of Health, Yale University, University of Ottawa, Ottawa Hospital Research Institute, University of Exeter, NIHR Applied Research Collaboration South West Peninsula
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Funders: Swiss Data Science Center, Ford Foundation, American Cancer Society, Bill and Melinda Gates Foundation, Robert Wood Johnson Foundation, California Institute for Regenerative Medicine, University of Pennsylvania, Villanova University, Arizona Department of Health Services, Lawson Health Research Institute, Karlsruhe Institute of Technology, Prince Sattam bin Abdulaziz University, Wellcome Trust, Comunidad de Madrid, Imperial Health Charity, Health Commission of Hebei Province, Margareta af Ugglas Foundation, Cancer Research UK, National Institute for Health and Care Research, Leverhulme Trust, European Commission, University of Edinburgh, University of Birmingham, Australian Cancer Research Foundation, Cancer Institute NSW, Council of Scientific and Industrial Research, India, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, University of New South Wales, National Natural Science Foundation of China, Österreichischen Akademie der Wissenschaften, Academy of Finland, Austrian Science Fund, Eidgenössische Technische Hochschule Zürich, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Natural Science Foundation of Fujian Province, Ministry of Agriculture, Food and Rural Affairs, Korea Health Industry Development Institute, National Research Foundation of Korea, King Abdulaziz University, Vetenskapsrådet, Universiti Malaya, Narodowym Centrum Nauki, National Research Council of Thailand, Universidad de Antioquia, Norges Forskningsråd, Bureau de Recherches Géologiques et Minières, Medicinska Forskningsrådet, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Agence Nationale pour la Gestion des Déchets Radioactifs, Vontobel-Stiftung, Novo Nordisk Fonden, University of Phayao, Indian Institute of Science Education and Research Mohali, Versus Arthritis, Olga Mayenfisch Stiftung, Ministry of SMEs and Startups, Ministry of Science and ICT, South Korea, Fundación Palarq, Uniscientia Foundation, Kinghorn Foundation, Arizona Biomedical Research Commission, National Institutes of Health, Canadian Institutes of Health Research, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, Australian Research Council, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, Schulich School of Medicine and Dentistry, NIHR Imperial Biomedical Research Centre, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Disability, Independent Living, and Rehabilitation Research, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Economic Research Institute for ASEAN and East Asia, Saint-Brieuc Armor Agglomération
OpenAlex ID: W7161945331