Abstract
Background: Central to the design of a randomised controlled trial is the calculation of the number of participants needed. This is typically achieved by specifying a target difference and calculating the corresponding sample size, which provides reassurance that the trial will have the required statistical power (at the planned statistical significance level) to identify whether a difference of a particular magnitude exists. Beyond pure statistical or scientific concerns, it is ethically imperative that an appropriate number of participants should be recruited. Despite the critical role of the target difference for the primary outcome in the design of randomised controlled trials, its determination has received surprisingly little attention. This article provides guidance on the specification of the target difference for the primary outcome in a sample size calculation for a two parallel group randomised controlled trial with a superiority question.
Methods: This work was part of the DELTA (Difference ELicitation in TriAls) project. Draft guidance was developed by the project steering and advisory groups utilising the results of the systematic review and surveys. Findings were circulated and presented to members of the combined group at a face-to-face meeting, along with a proposed outline of the guidance document structure, containing recommendations and reporting items for a trial protocol and report. The guidance and was subsequently drafted and circulated for further comment before finalisation.
Results: Guidance on specification of a target difference in the primary outcome for a two group parallel randomised controlled trial was produced. Additionally, a list of reporting items for protocols and trial reports was generated.
Conclusions: Specification of the target difference for the primary outcome is a key component of a randomized controlled trial sample size calculation. There is a need for better justification of the target difference and reporting of its specification.
| Original language | English |
|---|---|
| Article number | 12 |
| Number of pages | 7 |
| Journal | Trials |
| Volume | 16 |
| DOIs | |
| Publication status | Published - 15 Jan 2015 |
Bibliographical note
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Acknowledgements
The authors would like to acknowledge the other members of the DELTA group (Kirsten Harrild, Temitope E Adewuyi and Cynthia Fraser) and the advisory group who were involved in the wider project (Adrian Grant and Marion Campbell). Funding was received from the MRC/NIHR Methodology Research Panel which is jointly funded by the MRC (reference number: G0902147) and Health Technology Assessment (HTA) (project number: 06/98/01). Jonathan Cook held MRC training (reference number: G0601938) and methodology (reference number: G1002292) fellowships while this research was undertaken. 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.
Keywords
- target difference
- clinically important difference
- sample size
- randomised controlled trial
- guidance
- sample-size calculation
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