Methods for specifying the target difference in a randomised controlled trial: the Difference ELicitation in TriAls (DELTA) systematic review.
BACKGROUND
Randomised controlled trials (RCTs) are widely accepted as the preferred study design for evaluating healthcare interventions. When the sample size is determined, a (target) difference is typically specified that the RCT is designed to detect. This provides reassurance that the study will be informative, i.e., should such a difference exist, it is likely to be detected with the required statistical precision. The aim of this review was to identify potential methods for specifying the target difference in an RCT sample size calculation.


RESULTS
A comprehensive systematic review of medical and non-medical literature was carried out for methods that could be used to specify the target difference for an RCT sample size calculation. The databases searched were MEDLINE, MEDLINE In-Process, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, the Education Resources Information Center (ERIC), and Scopus (for in-press publications); the search period was from 1966 or the earliest date covered, to between November 2010 and January 2011. Additionally, textbooks addressing the methodology of clinical trials and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) tripartite guidelines for clinical trials were also consulted. A narrative synthesis of methods was produced. Studies that described a method that could be used for specifying an important and/or realistic difference were included. The search identified 11,485 potentially relevant articles from the databases searched. Of these, 1,434 were selected for full-text assessment, and a further nine were identified from other sources. Fifteen clinical trial textbooks and the ICH tripartite guidelines were also reviewed. In total, 777 studies were included, and within them, seven methods were identified-anchor, distribution, health economic, opinion-seeking, pilot study, review of the evidence base, and standardised effect size.


CONCLUSIONS
A variety of methods are available that researchers can use for specifying the target difference in an RCT sample size calculation. Appropriate methods may vary depending on the aim (e.g., specifying an important difference versus a realistic difference), context (e.g., research question and availability of data), and underlying framework adopted (e.g., Bayesian versus conventional statistical approach). Guidance on the use of each method is given. No single method provides a perfect solution for all contexts.
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
Jenni
J
Hislop
Academic Urology Unit, University of Aberdeen, Aberdeen, United Kingdom.
Temitope E
TE
Adewuyi
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
Luke D
LD
Vale
Population Health, University of Aberdeen, Aberdeen, United Kingdom.
Kirsten
K
Harrild
Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom.
Cynthia
C
Fraser
Warwick Evidence, University of Warwick, Coventry, United Kingdom.
Tara
T
Gurung
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
Douglas G
DG
Altman
Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom.
Andrew H
AH
Briggs
Population Health, University of Aberdeen, Aberdeen, United Kingdom; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Peter
P
Fayers
Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom.
Craig R
CR
Ramsay
Centre for Healthcare Randomised Trials, University of Aberdeen, Aberdeen, United Kingdom.
John D
JD
Norrie
Faculty of Health, University of East Anglia, Norwich, United Kingdom.
Ian M
IM
Harvey
National University of Ireland, Galway, Ireland.
Brian
B
Buckley
Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom; Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
Jonathan A
JA
Cook
D019317:Evidence-Based Medicine; D005104:Expert Testimony; D006801:Humans; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012015:Reference Standards