Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop
Background: The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated...
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NIHR Journals Library
2019-10-01
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Series: | Health Technology Assessment |
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Online Access: | https://doi.org/10.3310/hta23600 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 CF Wilson Graeme MacLennan Nigel Stallard Joanne C Rothwell Martin Bland Louise Brown Craig R Ramsay Andrew Cook David Armstrong Douglas Altman Luke D Vale |
spellingShingle |
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 CF Wilson Graeme MacLennan Nigel Stallard Joanne C Rothwell Martin Bland Louise Brown Craig R Ramsay Andrew Cook David Armstrong Douglas Altman Luke D Vale Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop Health Technology Assessment sample size research design minimal clinically important difference randomised controlled trials peer review |
author_facet |
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 CF Wilson Graeme MacLennan Nigel Stallard Joanne C Rothwell Martin Bland Louise Brown Craig R Ramsay Andrew Cook David Armstrong Douglas Altman Luke D Vale |
author_sort |
Jonathan A Cook |
title |
Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop |
title_short |
Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop |
title_full |
Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop |
title_fullStr |
Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop |
title_full_unstemmed |
Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop |
title_sort |
practical help for specifying the target difference in sample size calculations for rcts: the delta2 five-stage study, including a workshop |
publisher |
NIHR Journals Library |
series |
Health Technology Assessment |
issn |
1366-5278 2046-4924 |
publishDate |
2019-10-01 |
description |
Background: The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the ‘target difference’ and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups. Objective: The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives. Methods: The Difference ELicitation in TriAls2 (DELTA2) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document. Results: Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered. Conclusions: Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items. Funding: Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC–National Institute for Health Research Methodology Research programme. |
topic |
sample size research design minimal clinically important difference randomised controlled trials peer review |
url |
https://doi.org/10.3310/hta23600 |
work_keys_str_mv |
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doaj-cba0e59595b74186aa0898150edfed892020-11-25T00:49:58ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242019-10-01236010.3310/hta23600NIHR127268Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshopJonathan A Cook0Steven A Julious1William Sones2Lisa V Hampson3Catherine Hewitt4Jesse A Berlin5Deborah Ashby6Richard Emsley7Dean A Fergusson8Stephen J Walters9Edward CF Wilson10Graeme MacLennan11Nigel Stallard12Joanne C Rothwell13Martin Bland14Louise Brown15Craig R Ramsay16Andrew Cook17David Armstrong18Douglas Altman19Luke D Vale20Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UKMedical Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UKCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UKStatistical Methodology and Consulting, Novartis Pharma AG, Basel, SwitzerlandYork Trials Unit, Department of Health Sciences, University of York, York, UKJohnson & Johnson, Titusville, NJ, USAImperial Clinical Trials Unit, Imperial College London, London, UKDepartment of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UKClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, CanadaMedical Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UKCambridge Centre for Health Services Research, Cambridge Clinical Trials Unit University of Cambridge, Cambridge, UKCentre for Healthcare Randomised Trials, University of Aberdeen, Aberdeen, UKWarwick Medical School, Statistics and Epidemiology, University of Warwick, Coventry, UKMedical Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UKDepartment of Health Sciences, University of York, York, UKMRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKWessex Institute, University of Southampton, Southampton, UKSchool of Population Health and Environmental Sciences, King’s College London, London, UKCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UKHealth Economics Group, Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UKBackground: The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the ‘target difference’ and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups. Objective: The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives. Methods: The Difference ELicitation in TriAls2 (DELTA2) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document. Results: Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered. Conclusions: Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items. Funding: Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC–National Institute for Health Research Methodology Research programme.https://doi.org/10.3310/hta23600sample sizeresearch designminimal clinically important differencerandomised controlled trialspeer review |