DELTA2 guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial
Jonathan A. Cook,
Steven A. Julious,
William Sones,
Lisa V. Hampson,
Catherine Hewitt,
Jesse A. Berlin,
Deborah Ashby,
Richard Emsley,
Dean A. Fergusson,
Stephen J. Walters,
Edward C. F. Wilson,
Graeme Maclennan,
Nigel Stallard,
Joanne C. Rothwell,
Martin Bland,
Louise Brown,
Craig R. Ramsay,
Andrew Cook,
David Armstrong,
Doug Altman,
Luke D. Vale
Affiliations
Jonathan A. Cook
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre
Steven A. Julious
Medical Statistics Group, ScHARR, The University of Sheffield
William Sones
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre
Lisa V. Hampson
Statistical Methodology and Consulting, Novartis
Catherine Hewitt
Department of Health Sciences, Seebohm Rowntree Building, University of York
Jesse A. Berlin
Johnson & Johnson
Deborah Ashby
Imperial Clinical Trials Unit, School of Public Health, Imperial College London
Richard Emsley
Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
Dean A. Fergusson
Clinical Epidemiology Program, Ottawa Hospital Research Institute
Stephen J. Walters
Medical Statistics Group, ScHARR, The University of Sheffield
Edward C. F. Wilson
Cambridge Centre for Health Services Research & Cambridge Clinical Trials Unit, University of Cambridge, Institute of Public Health
Graeme Maclennan
The Centre for Healthcare Randomised Trials (CHaRT), Health Sciences Building, University of Aberdeen
Nigel Stallard
Warwick Medical School - Statistics and Epidemiology, University of Warwick
Joanne C. Rothwell
Medical Statistics Group, ScHARR, The University of Sheffield
Martin Bland
Department of Health Sciences, Seebohm Rowntree Building, University of York
Louise Brown
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology
Craig R. Ramsay
Health Services Research Unit, University of Aberdeen
Andrew Cook
Public Health Medicine and Fellow in Health Technology Assessment, Wessex Institute, University of Southampton
David Armstrong
School of Population Health & Environmental Sciences, Faculty of Life Sciences and Medicine, Kings College London
Doug Altman
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre
Luke D. Vale
Health Economics Group, Institute of Health & Society, Newcastle University
Abstract Background A key step in the design of a RCT is the estimation of the number of participants needed in the study. The most common approach is to specify a target difference between the treatments for the primary outcome and then calculate the required sample size. The sample size is chosen to ensure that the trial will have a high probability (adequate statistical power) of detecting a target difference between the treatments should one exist. The sample size has many implications for the conduct and interpretation of the study. Despite the critical role that the target difference has in the design of a RCT, the way in which it is determined has received little attention. In this article, we summarise the key considerations and messages from new guidance for researchers and funders on specifying the target difference, and undertaking and reporting a RCT sample size calculation. This article on choosing the target difference for a randomised controlled trial (RCT) and undertaking and reporting the sample size calculation has been dual published in the BMJ and BMC Trials journals Methods The DELTA2 (Difference ELicitation in TriAls) project comprised five major components: systematic literature reviews of recent methodological developments (stage 1) and existing funder guidance (stage 2); a Delphi study (stage 3); a two-day consensus meeting bringing together researchers, funders and patient representatives (stage 4); and the preparation and dissemination of a guidance document (stage 5). Results and Discussion The key messages from the DELTA2 guidance on determining the target difference and sample size calculation for a randomised caontrolled trial are presented. Recommendations for the subsequent reporting of the sample size calculation are also provided.
