{
  "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.",
  "authors": [
    {
      "affiliations": [
        "MRC Clinical Trials Unit at University College London, London, UK"
      ],
      "name": "Brennan C Kahan"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland",
        "Institute of Medical Statistics, Centre for Medical Data Science, Medical University of Vienna, Vienna, Austria"
      ],
      "name": "Frank Bretz"
    },
    {
      "affiliations": [
        "MRC Clinical Trials Unit at University College London, London, UK"
      ],
      "name": "Andrew Copas"
    },
    {
      "affiliations": [
        "MRC Clinical Trials Unit at University College London, London, UK",
        "Center for Clinical Trials Innovation, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
      ],
      "name": "Michael O Harhay"
    },
    {
      "affiliations": [
        "Department of Applied Health Sciences, School of Health Sciences, College and Medicine and Health, University of Birmingham, Birmingham, UK"
      ],
      "name": "Gary S Collins"
    },
    {
      "affiliations": [
        "Palliative and Advanced Illness Research Center, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
      ],
      "name": "Melanie Bahti"
    },
    {
      "affiliations": [
        "MRC Clinical Trials Unit at University College London, London, UK"
      ],
      "name": "Dongquan Bi"
    },
    {
      "affiliations": [
        "Aberdeen Centre for Evaluation, University of Aberdeen, Aberdeen, UK"
      ],
      "name": "Marion K Campbell"
    },
    {
      "affiliations": [
        "Center for Clinical Trials Innovation, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA",
        "Palliative and Advanced Illness Research Center, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
      ],
      "name": "Katherine R Courtright"
    },
    {
      "affiliations": [
        "Gillings School of Global Public Health, UNC Chapel Hill, Chapel Hill, NC, USA",
        "The BMJ, London, UK"
      ],
      "name": "Timothy Feeney"
    },
    {
      "affiliations": [
        "School of Public Health and Preventive Medicine, Monash University"
      ],
      "name": "Andrew B Forbes"
    },
    {
      "affiliations": [
        "Departments of Medicine, Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"
      ],
      "name": "Amit X Garg"
    },
    {
      "affiliations": [
        "Center for Clinical Trials Innovation, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA",
        "Palliative and Advanced Illness Research Center, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
      ],
      "name": "Scott D Halpern"
    },
    {
      "affiliations": [
        "Department of Biostatistics, University of Washington, Seattle, WA, USA"
      ],
      "name": "Patrick J Heagerty"
    },
    {
      "affiliations": [
        "Applied Health Research, School of Health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK"
      ],
      "name": "Karla Hemming"
    },
    {
      "affiliations": [
        "Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK"
      ],
      "name": "Sally Hopewell"
    },
    {
      "affiliations": [
        "Department of Biostatistics, University of Washington, Seattle, WA, USA"
      ],
      "name": "James P Hughes"
    },
    {
      "affiliations": [
        "National Institutes of Health, Bethesda, MD, USA"
      ],
      "name": "David M Murray"
    },
    {
      "affiliations": [
        "Section of General Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, USA",
        "Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA"
      ],
      "name": "Joseph S Ross"
    },
    {
      "affiliations": [
        "Patient author, UCL MRC Clinical Trials Unit-Methodological Patient Advisory Group, London, UK"
      ],
      "name": "Derek Stewart"
    },
    {
      "affiliations": [
        "Methodological and Implementation Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada",
        "School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada"
      ],
      "name": "Monica Taljaard"
    },
    {
      "affiliations": [
        "NIHR Applied Research Collaboration South West Peninsula, University of Exeter, Exeter, UK"
      ],
      "name": "Obioha C Ukoumunne"
    },
    {
      "affiliations": [
        "Palliative and Advanced Illness Research Center, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
      ],
      "name": "Catherine L Auriemma"
    },
    {
      "affiliations": [
        "Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA"
      ],
      "name": "Fan Li"
    }
  ],
  "title": "CRT-Estimands Framework: consensus based extension of the ICH E9(R1) addendum for cluster randomised trials",
  "uid": "7eeb560e-c7cf-515f-8307-ed20676965ad"
}