DELTA 2 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

doi:10.1136/bmj.k3750

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 AltmanLuke D. Vale

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Randomised controlled trials are considered to be the best method to assess comparative clinical efficacy and effectiveness, and can be a key source of data for estimating cost effectiveness. Central to the design of a randomised controlled trial is an a priori sample size calculation, which ensures that the study has a high probability of achieving its prespecified main objective. Beyond pure statistical or scientific concerns, it is ethically imperative that an appropriate number of study participants be recruited, to avoid imposing the burdens of a clinical trial on more patients than necessary. The scientific concern is satisfied and the ethical imperative is further addressed by the specification of a target difference between treatments that is considered realistic or important by one or more key stakeholder groups. The sample size calculation ensures that the trial will have the required statistical power to identify whether a difference of a particular magnitude exists. In this article, the key messages from the DELTA 2 guidance on determining the target difference and sample size calculation for a randomised controlled trial are presented. Recommendations for the subsequent reporting of the sample size calculation are also provided.

Original language	English
Article number	k3750
Journal	BMJ
Volume	363
DOIs	https://doi.org/10.1136/bmj.k3750
Publication status	Published - 5 Nov 2018

Bibliographical note

Funding: Funding for this work was received from the MRC-NIHR UK Methodology Research Programme in response to an open commissioned call for an effect size methodology state-of-the-art workshop. The Health Services Research Unit, Institute of Applied Health Sciences (University of Aberdeen), is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The funders had no involvement in study design, collection, analysis, and interpretation of data; reporting; or the decision to publish.

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DELTA2 guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.
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Cook, J. A., Julious, S. A., Sones, W., Hampson, L. V., Hewitt, C., Berlin, J. A., Ashby, D., Emsley, R., Fergusson, D. A., Walters, S. J., Wilson, E. C. F., MacLennan, G., Stallard, N., Rothwell, J. C., Bland, M., Brown, L., Ramsay, C. R., Cook, A., Armstrong, D., ... Vale, L. D. (2018). DELTA² guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial. BMJ, 363, Article k3750. https://doi.org/10.1136/bmj.k3750

Cook, JA, Julious, SA, Sones, W, Hampson, LV, Hewitt, C, Berlin, JA, Ashby, D, Emsley, R, Fergusson, DA, Walters, SJ, Wilson, ECF, MacLennan, G, Stallard, N, Rothwell, JC, Bland, M, Brown, L, Ramsay, CR, Cook, A, Armstrong, D, Altman, D & Vale, LD 2018, 'DELTA² guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial', BMJ, vol. 363, k3750. https://doi.org/10.1136/bmj.k3750

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abstract = "Randomised controlled trials are considered to be the best method to assess comparative clinical efficacy and effectiveness, and can be a key source of data for estimating cost effectiveness. Central to the design of a randomised controlled trial is an a priori sample size calculation, which ensures that the study has a high probability of achieving its prespecified main objective. Beyond pure statistical or scientific concerns, it is ethically imperative that an appropriate number of study participants be recruited, to avoid imposing the burdens of a clinical trial on more patients than necessary. The scientific concern is satisfied and the ethical imperative is further addressed by the specification of a target difference between treatments that is considered realistic or important by one or more key stakeholder groups. The sample size calculation ensures that the trial will have the required statistical power to identify whether a difference of a particular magnitude exists. In this article, the key messages from the DELTA 2 guidance on determining the target difference and sample size calculation for a randomised controlled trial are presented. Recommendations for the subsequent reporting of the sample size calculation are also provided.",

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DELTA² guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial

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