Specifying the target difference in the primary outcome for a randomised controlled trial: guidance for researchers.
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 Draft guidance was developed by the project steering and advisory groups utilising the results of the systematic review and surveys.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.
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Oxford, OX3 7LD, UK. jonathan.cook@ndorms.ox.ac.uk.|Health Services Research Unit, University of Aberdeen, Health Sciences Building, Foresthill, Aberdeen, AB25 2ZD, UK. jonathan.cook@ndorms.ox.ac.uk.
Jonathan A
JA
Cook
Institute of Health and Society, Newcastle University, The Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK. jenni.hislop@newcastle.ac.uk.
Jenni
J
Hislop
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Oxford, OX3 7LD, UK. doug.altman@csm.ox.ac.uk.
Douglas G
DG
Altman
Population Health, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK. p.fayers@abdn.ac.uk.|Department of Cancer Research and Molecular, Norwegian University of Science and Technology, Mailbox 8905, Trondheim, N-7491, Norway. p.fayers@abdn.ac.uk.
Peter
P
Fayers
Health Economics and Health Technology Assessment, University of Glasgow, 1 Lilybank Gardens, Glasgow, G12 8RZ, UK. Andrew.briggs@glasgow.ac.uk.
Andrew H
AH
Briggs
Health Services Research Unit, University of Aberdeen, Health Sciences Building, Foresthill, Aberdeen, AB25 2ZD, UK. c.r.ramsay@abdn.ac.uk.
Craig R
CR
Ramsay
Centre for Healthcare Randomised Trials (CHaRT), University of Aberdeen, Health Sciences Building, Aberdeen, AB25 2ZD, UK. j.norrie@abdn.ac.uk.
John D
JD
Norrie
Faculty of Medicine and Health Sciences, University of East Anglia, Elizabeth Fry Building, Norwich Research Park, Norwich, NR4 7TJ, UK. Ian.harvey@uea.ac.uk.
Ian M
IM
Harvey
National University of Ireland, University Road, Galway, Ireland. briansbuckley@gmail.com.
Brian
B
Buckley
Clinical Epidemiology Program, Ottawa Hospital Research Institute, 725 Parkdale Avenue, Ottawa, ON, K1Y 4E9, Canada. dafergusson@ohri.ca.
Dean
D
Fergusson
Robertson Centre for Biostatistics, University of Glasgow, Boyd Orr Building, University Avenue, Glasgow, G12 8QQ, UK. ian.ford@glasgow.ac.uk.
Ian
I
Ford
Institute of Health and Society, Newcastle University, The Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK. luke.vale@newcastle.ac.uk.
Luke D
LD
Vale
D003627:Data Interpretation, Statistical; D023381:Endpoint Determination / Q000592:standards* / Q000706:statistics & numerical data; D006801:Humans; D017410:Practice Guidelines as Topic / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D018401:Sample Size; D016896:Treatment Outcome