The University of Southampton
University of Southampton Institutional Repository

Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop

Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop
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 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.
sample size, rct, trial, guidance
1366-5278
1-118
Cook, Jonathan
eb29ac3d-490b-4845-8756-dd600d97468c
Julious, Stephen
1d8d19d8-8c3b-4c60-b8c7-05784eda06cf
Sones, William
4fe7834b-79c9-4cc3-b1e4-92da2f138151
Hampson, Lisa
b23e1d2d-67f5-4571-8597-fa5143a0af51
Hewitt, C.
84327f37-15f5-4b58-b8bd-60c8fe9610ed
Berlin, Jesse
1a6e7264-125e-409e-9696-b96ed195bfd0
Ashby, Deborah
12a12757-6283-4323-a4b8-7f32b475847b
Emsley, Richard
befe7b94-728c-47aa-84db-4f066d5f4836
Fergusson, Dean
cacbc47a-9748-47f3-8ecd-583bed22925e
Walters, Stephen J.
aed7a87c-2c83-4a28-a68f-54bfecb3fa53
Wilson, Edward
771a89ab-d773-4ead-b220-c529a5163ad1
MacLennan, Graeme
209593f8-0b7c-44fd-9abc-c1ea575b6c61
Stallard, Nigel
d9b9b07e-f2a5-4cfe-bc8b-d6e614cdea1c
Rothwell, J
61063934-2080-464a-a09f-c117a19478e7
Bland, J.Martin
ed98b825-f235-4fab-8b9a-19b66a1d9a46
Brown, Louise
f991f4f7-ccfb-4b7c-8944-5f4f5c8ee186
Ramsay, Craig
2f8071ed-9d54-4d8a-9473-d8fa15d5e6d5
Cook, Andrew
ab9c7bb3-974a-4db9-b3c2-9942988005d5
Armstrong, David
9deb1102-2dfc-4f28-aaba-fc51ca224122
Altman, Douglas
7f18f3b2-09d7-4a8c-8ec0-659e9d560e9c
Vale, Luke
d0be6b50-51db-4d59-9094-17dcb5582bd8
Cook, Jonathan
eb29ac3d-490b-4845-8756-dd600d97468c
Julious, Stephen
1d8d19d8-8c3b-4c60-b8c7-05784eda06cf
Sones, William
4fe7834b-79c9-4cc3-b1e4-92da2f138151
Hampson, Lisa
b23e1d2d-67f5-4571-8597-fa5143a0af51
Hewitt, C.
84327f37-15f5-4b58-b8bd-60c8fe9610ed
Berlin, Jesse
1a6e7264-125e-409e-9696-b96ed195bfd0
Ashby, Deborah
12a12757-6283-4323-a4b8-7f32b475847b
Emsley, Richard
befe7b94-728c-47aa-84db-4f066d5f4836
Fergusson, Dean
cacbc47a-9748-47f3-8ecd-583bed22925e
Walters, Stephen J.
aed7a87c-2c83-4a28-a68f-54bfecb3fa53
Wilson, Edward
771a89ab-d773-4ead-b220-c529a5163ad1
MacLennan, Graeme
209593f8-0b7c-44fd-9abc-c1ea575b6c61
Stallard, Nigel
d9b9b07e-f2a5-4cfe-bc8b-d6e614cdea1c
Rothwell, J
61063934-2080-464a-a09f-c117a19478e7
Bland, J.Martin
ed98b825-f235-4fab-8b9a-19b66a1d9a46
Brown, Louise
f991f4f7-ccfb-4b7c-8944-5f4f5c8ee186
Ramsay, Craig
2f8071ed-9d54-4d8a-9473-d8fa15d5e6d5
Cook, Andrew
ab9c7bb3-974a-4db9-b3c2-9942988005d5
Armstrong, David
9deb1102-2dfc-4f28-aaba-fc51ca224122
Altman, Douglas
7f18f3b2-09d7-4a8c-8ec0-659e9d560e9c
Vale, Luke
d0be6b50-51db-4d59-9094-17dcb5582bd8

Cook, Jonathan, Julious, Stephen, Sones, William, Hampson, Lisa, Hewitt, C., Berlin, Jesse, Ashby, Deborah, Emsley, Richard, Fergusson, Dean, Walters, Stephen J., Wilson, Edward, MacLennan, Graeme, Stallard, Nigel, Rothwell, J, Bland, J.Martin, Brown, Louise, Ramsay, Craig, Cook, Andrew, Armstrong, David, Altman, Douglas and Vale, Luke (2019) Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop. Health Technology Assessment, 23 (60), 1-118. (doi:10.3310/hta23600).

Record type: Article

Abstract

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.

Text
3030850 - Version of Record
Available under License Other.
Download (1MB)

More information

Published date: October 2019
Keywords: sample size, rct, trial, guidance

Identifiers

Local EPrints ID: 435426
URI: http://eprints.soton.ac.uk/id/eprint/435426
ISSN: 1366-5278
PURE UUID: 88e63f78-fc93-4514-a1fa-32a3da1c699f
ORCID for Andrew Cook: ORCID iD orcid.org/0000-0002-6680-439X

Catalogue record

Date deposited: 06 Nov 2019 17:30
Last modified: 11 May 2024 01:41

Export record

Altmetrics

Contributors

Author: Jonathan Cook
Author: Stephen Julious
Author: William Sones
Author: Lisa Hampson
Author: C. Hewitt
Author: Jesse Berlin
Author: Deborah Ashby
Author: Richard Emsley
Author: Dean Fergusson
Author: Stephen J. Walters
Author: Edward Wilson
Author: Graeme MacLennan
Author: Nigel Stallard
Author: J Rothwell
Author: J.Martin Bland
Author: Louise Brown
Author: Craig Ramsay
Author: Andrew Cook ORCID iD
Author: David Armstrong
Author: Douglas Altman
Author: Luke Vale

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×