Specifying the target difference in the primary outcome for a randomised controlled trial: guidance for researchers

Cook, Jonathan A; Hislop, Jenni; Altman, Douglas G; Fayers, Peter; Briggs, Andrew H; Ramsay, Craig R; Norrie, John D; Harvey, Ian M; Buckley, Brian; Fergusson, Dean; Ford, Ian; Vale, Luke D; for the DELTA group

doi:10.1186/s13063-014-0526-8

Cited by 66Statistical Methods in Clinical TrialsMeta-analysis and systematic reviewsStatistical Methods in Epidemiology

Specifying the target difference in the primary outcome for a randomised controlled trial: guidance for researchers

Open access

Cook, Jonathan A, Hislop, Jenni, Altman, Douglas G, Fayers, Peter, Briggs, Andrew H, Ramsay, Craig R, Norrie, John D, Harvey, Ian M +5 more·2015·Trials

DOI 10.1186/s13063-014-0526-8PMC PMC4302137

Open this paper in CoChat — free account Open PDF

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 Draft guidance was developed by the project steering and advisory groups utilising the results of the systematic review and surveys.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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1186/s13063-014-0526-8

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The sample size calculation is a key component in the design of a randomised trial.
“The sample size calculation is a key component in the design of a randomised trial.290 291”
From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [290]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
the CONSORT Group, Schulz, K. F., Altman, D. G., & Moher, D. (2010) · BMC Medicine · doi:10.1186/1741-7015-8-18 · Cited by 13,371 · see citing works
Self-citation
CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
Schulz, K. F., Altman, D. G., Moher, D., & for the CONSORT Group (2010) · BMJ · doi:10.1136/bmj.c332 · Cited by 9,329 · see citing works
Self-citation
SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials
Chan, A.-W., Tetzlaff, J. M., Altman, D. G., Laupacis, A., Gøtzsche, P. C., Krleža-Jerić, K., Hróbjartsson, A., Mann, H., Dickersin, K., Berlin, J. A., et al. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-3-201302050-00583 · Cited by 7,363 · see citing works
Self-citation
The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration
Altman, D. G., Schulz, K. F., Moher, D., Egger, M., Davidoff, F., Elbourne, D., Gøtzsche, P. C., Lang, T., & for the CONSORT Group (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-8-200104170-00012 · Cited by 3,835 · see citing works
Self-citation
Clinical Trials: A Practical Approach.
Hill, I. D., & Pocock, S. (1984) · Biometrics · doi:10.2307/2531186 · Cited by 2,918 · see citing works
Fundamentals of Clinical Trials
Friedman, L. M., Furberg, C. D., DeMets, D. L., Reboussin, D. M., & Granger, C. B. (2015) · doi:10.1007/978-3-319-18539-2 · Cited by 2,237 · see citing works
Understanding the minimum clinically important difference: A review of concepts and methods
Copay, A. G., Subach, B. R., Glassman, S. D., Polly, D. W., & Schuler, T. C. (2007) · The Spine Journal · doi:10.1016/j.spinee.2007.01.008 · Cited by 1,662 · see citing works
What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies
McDonald, A. M., Knight, R. C., Campbell, M. K., Entwistle, V. A., Grant, A. M., Cook, J. A., Elbourne, D. R., Francis, D., Garcia, J., Roberts, I., et al. (2006) · Trials · doi:10.1186/1745-6215-7-9 · Cited by 946 · see citing works
Self-citation
Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries
Taggart, D. P., D’Amico, R., & Altman, D. G. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06069-x · Cited by 733 · see citing works
Self-citation
Arbitrary metrics in psychology
Blanton, H., & Jaccard, J. (2006) · American Psychologist · doi:10.1037/0003-066x.61.1.27 · Cited by 681 · see citing works
Macular hole surgery with and without internal limiting membrane peeling
Brooks, H. L. (2000) · Ophthalmology · doi:10.1016/s0161-6420(00)00331-6 · Cited by 645 · see citing works
Many faces of the minimal clinically important difference (MCID): a literature review and directions for future research.
Beaton, D., Boers, M., & Wells, G. (2002) · Current Opinion in Rheumatology · doi:10.1097/00002281-200203000-00006 · Cited by 547 · see citing works
Fundamentals of Clinical Trials
Friedman, L. M., Furberg, C. D., & DeMets, D. L. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1586-3 · Cited by 532 · see citing works
The Concept of Clinically Meaningful Difference in Health-Related Quality of Life Research
Hays, R. D., & Woolley, J. M. (2000) · PharmacoEconomics · doi:10.2165/00019053-200018050-00001 · Cited by 491 · see citing works
Conservative management for postprostatectomy urinary incontinence
Anderson, C. A., Omar, M. I., Campbell, S. E., Hunter, K. F., Cody, J. D., & Glazener, C. M. A. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001843.pub5 · Cited by 473 · see citing works
Minimal clinically important differences: review of methods.
Wells, G. A., Beaton, D., Shea, B., Boers, M., Simon, L. S., Strand, V., Brooks, P., & Tugwell, P. (2001) · PubMed · Cited by 376 · see citing works
Reporting of sample size calculation in randomised controlled trials: review
Charles, P., Giraudeau, B., Dechartres, A., Baron, G., & Ravaud, P. (2009) · BMJ · doi:10.1136/bmj.b1732 · Cited by 274 · see citing works
Internal Limiting Membrane Peeling versus No Peeling for Idiopathic Full-Thickness Macular Hole: A Pragmatic Randomized Controlled Trial
Lois, N., Burr, J. M., Norrie, J. D., Vale, L. D., Cook, J. A., McDonald, A. M., Boachie, C., Ternent, L., & McPherson, G. C. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6287 · Cited by 256 · see citing works
Self-citation
The Rise and Fall of the Shah
Campbell, J. C., Saikal, A., Pahlavi, A., Hoveyda, F., & Forbis, W. H. (1980) · Foreign Affairs · doi:10.2307/20040636 · Cited by 253 · see citing works
Current sample size conventions: Flaws, harms, and alternatives
Bacchetti, P. (2010) · BMC Medicine · doi:10.1186/1741-7015-8-17 · Cited by 233 · see citing works
Sample Sizes for Clinical Trials
Julious, S. A. (2009) · Chapman & Hall/CRC eBooks · doi:10.1201/9781584887409 · Cited by 227 · see citing works
Effect of autologous platelet concentrate in surgery for idiopathic macular hole
Pâques, M., Chastang, C., Mathis, A., Sahel, J., Massin, P., Dosquet, C., Korobelnik, J., Gargasson, J. L., & Gaudric, A. (1999) · Ophthalmology · doi:10.1016/s0161-6420(99)00512-6 · Cited by 199 · see citing works
Assessing methods to specify the target difference for a randomised controlled trial: DELTA (Difference ELicitation in TriAls) review
Cook, J., Hislop, J., Adewuyi, T., Harrild, K., Altman, D., Ramsay, C., Fraser, C., Buckley, B., Fayers, P., Harvey, I., et al. (2014) · Health Technology Assessment · doi:10.3310/hta18280 · Cited by 194 · see citing works
Self-citation
Introduction to Randomized Controlled Clinical Trials
Matthews, J. N. S. (2006) · Chapman & Hall/CRC eBooks · doi:10.1201/9781420011302 · Cited by 178 · see citing works
Sufficiently Important Difference: Expanding the Framework of Clinical Significance
Barrett, B. P., Brown, D. P., Mundt, M. P., & Brown, R. (2005) · Medical Decision Making · doi:10.1177/0272989x05276863 · Cited by 173 · see citing works
Urinary incontinence in men after formal one-to-one pelvic-floor muscle training following radical prostatectomy or transurethral resection of the prostate (MAPS): two parallel randomised controlled trials
Glazener, C. M. A., Boachie, C., Buckley, B. S., Cochrane, C., Dorey, G., GRANT, A. M., Hagen, S., Kilonzo, M. M., McDonald, A. M., McPherson, G. C., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60751-4 · Cited by 129 · see citing works
Self-citation
[Macular hole surgery with and without internal limiting membrane peeling].
Castro Navarro, J., & González-Castaño, C. (2003) · PubMed · Cited by 119 · see citing works
Surgery with disc prosthesis versus rehabilitation in patients with low back pain and degenerative disc: two year follow-up of randomised study
Hellum, C., Johnsen, L. G., Storheim, K., Nygaard, O. P., Brox, J. I., Rossvoll, I., Ro, M., Sandvik, L., Grundnes, O., & and the Norwegian Spine Study Group (2011) · BMJ · doi:10.1136/bmj.d2786 · Cited by 116 · see citing works
Protocol for the Arterial Revascularisation Trial (ART). A randomised trial to compare survival following bilateral versus single internal mammary grafting in coronary revascularisation [ISRCTN46552265]
the ART Investigators, Taggart, D. P., Lees, B., Gray, A. M., Altman, D. G., Flather, M. D., & Channon, K. M. (2006) · Trials · doi:10.1186/1745-6215-7-7 · Cited by 115 · see citing works
Self-citation
Conservative management for postprostatectomy urinary incontinence
Hunter, K. F., Moore, K., & Glazener, C. M. A. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001843.pub3 · Cited by 100 · see citing works
Optimal clinical trial design using value of information methods with imperfect implementation
Willan, A. R., & Eckermann, S. D. (2009) · Health Economics · doi:10.1002/hec.1493 · Cited by 97 · see citing works
Conservative management for post prostatectomy urinary incontinence
Moore, K., Cody, D., & Glazener, C. (2001) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001843 · Cited by 86 · see citing works
Statistical Significance Versus Clinical Importance
van Tulder, M. W., Malmivaara, A. O. V., Hayden, J. A., & Koes, B. W. (2007) · Spine · doi:10.1097/brs.0b013e3180b9ef49 · Cited by 83 · see citing works
Sample size determinations in original research protocols for randomised clinical trials submitted to UK research ethics committees: review
Clark, T., Berger, U., & Mansmann, U. (2013) · BMJ · doi:10.1136/bmj.f1135 · Cited by 68 · see citing works
The rise and fall of the “minimum clinically important difference”
Carragee, E. J. (2010) · The Spine Journal · doi:10.1016/j.spinee.2010.02.013 · Cited by 58 · see citing works
Sample size calculation for clinical trials: the impact of clinician beliefs
Fayers, P. M., Cuschieri, A., Fielding, J. W. L., Craven, J., Uscinska, B., & Freedman, L. S. (2000) · British Journal of Cancer · doi:10.1054/bjoc.1999.0902 · Cited by 47 · see citing works
Self-citation
Sample Sizes for Clinical Trials
Julious, S. A. (2023) · Chapman & Hall/CRC eBooks · doi:10.1201/9780429503658 · Cited by 44 · see citing works
Methods for Specifying the Target Difference in a Randomised Controlled Trial: The Difference ELicitation in TriAls (DELTA) Systematic Review
Hislop, J., Adewuyi, T. E., Vale, L. D., Harrild, K., Fraser, C. M., Gurung, T., Altman, D. G., Briggs, A. H., Fayers, P. M., Ramsay, C. R., et al. (2014) · PLoS Medicine · doi:10.1371/journal.pmed.1001645 · Cited by 36 · see citing works
Self-citation
A Bayesian cost–benefit approach to the determination of sample size in clinical trials
Kikuchi, T., Pezeshk, H., & Gittins, J. C. (2007) · Statistics in Medicine · doi:10.1002/sim.2965 · Cited by 31 · see citing works
Clinical Trial Methodology
Peace, K. E., & Chen, D. (2010) · Chapman & Hall/CRC eBooks · doi:10.1201/ebk1584889175 · Cited by 26 · see citing works
Letter to the Editor: Minimum clinically important difference
Mattei, T. A., & Fassett, D. R. (2011) · Journal of Neurosurgery Spine · doi:10.3171/2011.7.spine11531 · Cited by 17 · see citing works

Flagged first, then by citations

Sorted by citations

DELTA2 guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial
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., et al. (2018) · Trials · doi:10.1186/s13063-018-2884-0 · Cited by 197 · see citing works
Self-citation
SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials
Hróbjartsson, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · BMJ · doi:10.1136/bmj-2024-081660 · Cited by 171 · see citing works
Self-citation
Living systematic reviews: 3. Statistical methods for updating meta-analyses
Simmonds, M. C., Salanti, G., McKenzie, J. E., Elliott, J., Agoritsas, T., Hilton, J., Perron, C., Akl, E. A., Hodder, R. K., Pestridge, C., et al. (2017) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2017.08.008 · Cited by 145 · see citing works
DELTA<sup>2</sup> guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial
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., et al. (2018) · BMJ · doi:10.1136/bmj.k3750 · Cited by 148 · see citing works
Self-citation
Preventive Treatments for Psychosis: Umbrella Review (Just the Evidence)
Fusar-Poli, P., Davies, C., Solmi, M., Brondino, N., De Micheli, A., Kotlicka-Antczak, M., Shin, J. I., & Radua, J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00764 · Cited by 108 · see citing works
Minimal important change values for the Oxford Knee Score and the Forgotten Joint Score at 1 year after total knee replacement
Ingelsrud, L. H., Roos, E. M., Terluin, B., Gromov, K., Husted, H., & Troelsen, A. (2018) · Acta Orthopaedica · doi:10.1080/17453674.2018.1480739 · Cited by 91 · see citing works
Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation—a cluster randomized trial with 64,273 participants
Nørskov, A. K., Wetterslev, J., Rosenstock, C. V., Afshari, A., Astrup, G., Jakobsen, J. C., Thomsen, J. L., Bøttger, M., Ellekvist, M., Schousboe, B. M. B., et al. (2016) · British Journal of Anaesthesia · doi:10.1093/bja/aew057 · Cited by 78 · see citing works
A study of target effect sizes in randomised controlled trials published in the Health Technology Assessment journal
Rothwell, J. C., Julious, S. A., & Cooper, C. L. (2018) · Trials · doi:10.1186/s13063-018-2886-y · Cited by 73 · see citing works
Preparing for what the reporting checklists will not tell you: the PREPARE Trial guide for planning clinical research to avoid research waste
Bandholm, T., Christensen, R., Thorborg, K., Treweek, S. P., & Henriksen, M. (2017) · British Journal of Sports Medicine · doi:10.1136/bjsports-2017-097527 · Cited by 65 · see citing works
Living Systematic Reviews
Simmonds, M. C., Elliott, J., Synnot, A., & Turner, T. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1566-9_7 · Cited by 70 · see citing works
Important differences and meaningful changes for the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog)
Bell, M. L., Dhillon, H. M., Bray, V., & Vardy, J. L. (2018) · Journal of Patient-Reported Outcomes · doi:10.1186/s41687-018-0071-4 · Cited by 66 · see citing works
Potential effectiveness of copper surfaces in reducing health care–associated infection rates in a pediatric intensive and intermediate care unit: A nonrandomized controlled trial
Bettina Von Dessauer, G., Navarrete, M. S., Dona Benadof, F., Benavente, C., & Schmidt, M. G. (2016) · American Journal of Infection Control · doi:10.1016/j.ajic.2016.03.053 · Cited by 57 · see citing works
An RCT study comparing the clinical and radiological outcomes with the use of PLIF or TLIF after instrumented reduction in adult isthmic spondylolisthesis
Yang, E., Xu, J., Liu, X.-K., Jin, G.-Y., Xiao, W., Zeng, B., & Lian, X. (2015) · European Spine Journal · doi:10.1007/s00586-015-4341-z · Cited by 56 · see citing works
How do you design randomised trials for smaller populations? A framework
Parmar, M., Sydes, M. R., & Morris, T. P. (2016) · BMC Medicine · doi:10.1186/s12916-016-0722-3 · Cited by 48 · see citing works
Essential statistical principles of clinical trials of pain treatments
Dworkin, R. H., Evans, S. R., Mbowe, O. B., & McDermott, M. (2020) · PAIN Reports · doi:10.1097/pr9.0000000000000863 · Cited by 46 · see citing works
How should minimally important change scores for the Patient-Oriented Eczema Measure be interpreted? A validation using varied methods
Howells, L., Ratib, S., Chalmers, J. R., Bradshaw, L. E., Thomas, K. S., & the CLOTHES trial team (2018) · British Journal of Dermatology · doi:10.1111/bjd.16367 · Cited by 41 · see citing works
Animal models of cardiac arrest: A systematic review of bias and reporting
Fabian-Jessing, B. K., Vallentin, M. F., Secher, N., Hansen, F. B., Dezfulian, C., Granfeldt, A., & Andersen, L. W. (2018) · Resuscitation · doi:10.1016/j.resuscitation.2018.01.047 · Cited by 39 · see citing works
Predictors, outcomes, and statistical solutions of missing cases in web-based psychotherapy: methodological replication and elaboration study
Karin, E., Crane, M. F., Dear, B. F., Nielssen, O., Heller, G. Z., Kayrouz, R., & Titov, N. (2021) · JMIR Mental Health · doi:10.2196/22700 · Cited by 36 · see citing works
Sample size calculations are poorly conducted and reported in many randomized trials of hip and knee osteoarthritis: results of a systematic review
Copsey, B. J., Thompson, J., Vadher, K., Ali, U. M., Dutton, S., Fitzpatrick, R. M., Lamb, S. E., & Cook, J. A. (2018) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2018.08.013 · Cited by 33 · see citing works
Self-citation
Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop
Cook, J. A., Julious, S. A., Sones, W. R., Hampson, L. V., Hewitt, C. E., Berlin, J. A., Ashby, D., Emsley, R., Fergusson, D. A., Walters, S. J., et al. (2019) · Health Technology Assessment · doi:10.3310/hta23600 · Cited by 33 · see citing works
Self-citation
Internet delivery of intensive speech and language therapy for children with cerebral palsy: a pilot randomised controlled trial
Pennington, L., Stamp, E., Smith, J., Kelly, H., Parker, N. K., Stockwell, K., Aluko, P., Othman, M., Brittain, K., & Vale, L. D. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-024233 · Cited by 32 · see citing works
Self-citation
Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors
Murdaca, G., Greco, M., Vassallo, C., & Gangemi, S. (2020) · Clinical and Molecular Allergy · doi:10.1186/s12948-020-00131-8 · Cited by 27 · see citing works
New guidance to improve sample size calculations for trials: eliciting the target difference
Bell, M. L. (2018) · Trials · doi:10.1186/s13063-018-2894-y · Cited by 26 · see citing works
Structure–Function Relationships in the Rodent Streptozotocin-Induced Model for Diabetic Retinopathy: A Systematic Review
Lelytė, I., Ahmed, Z., Kaja, S., & Kalesnykas, G. (2022) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2021.0128 · Cited by 27 · see citing works
Patient-reported outcomes and target effect sizes in pragmatic randomized trials in ClinicalTrials.gov: A cross-sectional analysis
Vanderhout, S. M., Fergusson, D. A., Cook, J. A., & Taljaard, M. (2022) · PLoS Medicine · doi:10.1371/journal.pmed.1003896 · Cited by 26 · see citing works
Self-citation
Effect of a combined brief narrative exposure therapy with case management versus treatment as usual in primary care for patients with traumatic stress sequelae following intensive care medicine: study protocol for a multicenter randomized controlled trial (PICTURE)
on behalf of the PICTURE Study Group, Gensichen, J. S., Schultz, S., Adrion, C., Schmidt, K. F. R., Schauer, M., Lindemann, D., Unruh, N., Kosilek, R. P., Schneider, A., et al. (2018) · Trials · doi:10.1186/s13063-018-2853-7 · Cited by 25 · see citing works
Improving Power and Sample Size Calculation in Rehabilitation Trial Reports: A Methodological Assessment
Castellini, G., Gianola, S., Bonovas, S., & Moja, L. (2016) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2016.02.013 · Cited by 23 · see citing works
Research methodology for orthopaedic surgeons, with a focus on outcome
Lübbeke, A. (2018) · EFORT Open Reviews · doi:10.1302/2058-5241.3.170064 · Cited by 20 · see citing works
A Multicentered Randomized Controlled Trial Comparing the Effectiveness of Pain Treatment Communication Tools in Emergency Department Patients With Back or Kidney Stone Pain
Meisel, Z. F., Shofer, F., Dolan, A., Goldberg, E. B., Rhodes, K. V., Hess, E. P., Bellamkonda, V. R., Perrone, J., Cannuscio, C. C., Becker, L., et al. (2022) · American Journal of Public Health · doi:10.2105/ajph.2021.306511 · Cited by 18 · see citing works
Considerations for Clinical Trials Targeting the Myocardial Interstitium
Lewis, G. A., Dodd, S. R., Naish, J. H., Selvanayagam, J. B., Dweck, M. R., & Miller, C. (2019) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2019.03.034 · Cited by 18 · see citing works
Minimal clinically important difference in means in vulnerable populations: challenges and solutions
Peacock, J. L., Lo, J., Rees, J. R., & Sauzet, O. (2021) · BMJ Open · doi:10.1136/bmjopen-2021-052338 · Cited by 15 · see citing works
Ethical implications of excessive cluster sizes in cluster randomised trials
Hemming, K., Taljaard, M., Forbes, G., Eldridge, S. M., & Weijer, C. (2018) · BMJ Quality & Safety · doi:10.1136/bmjqs-2017-007164 · Cited by 14 · see citing works
The effect of core stability training with ball and balloon exercise on respiratory variables in chronic non-specific low back pain: An experimental study
Mohan, V., Paungmali, A., Sitilertpisan, P., Joseph, L., Omar, F. A., & Azhar, F. Z. (2020) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2020.07.007 · Cited by 15 · see citing works
Choosing the target difference (‘effect size’) for a randomised controlled trial - DELTA2 guidance protocol
Cook, J. A., Julious, S. A., Sones, W. R., Rothwell, J. C., Ramsay, C. R., Hampson, L. V., Emsley, R., Walters, S. J., Hewitt, C. E., Bland, M., et al. (2017) · Trials · doi:10.1186/s13063-017-1969-5 · Cited by 14 · see citing works
Self-citation
Choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial – the development of the DELTA2 guidance
Sones, W. R., Julious, S. A., Rothwell, J. C., Ramsay, C. R., Hampson, L. V., Emsley, R., Walters, S. J., Hewitt, C. E., Bland, M., Fergusson, D. A., et al. (2018) · Trials · doi:10.1186/s13063-018-2887-x · Cited by 13 · see citing works
Self-citation
Using Time Trade-Off Methods to Elicit Short-Term Utilities Associated with Treatments for Bulbar Urethral Stricture
for the OPEN trial investigators, Shen, J., Breckons, M., Vale, L. D., & Pickard, R. S. (2019) · PharmacoEconomics - Open · doi:10.1007/s41669-019-0133-4 · Cited by 11 · see citing works
Self-citation
Invasive urodynamic testing prior to surgical treatment for stress urinary incontinence in women: cost-effectiveness and value of information analyses in the context of a mixed methods feasibility study
on behalf of the INVESTIGATE-I studies group, Homer, T. M., Shen, J., Vale, L. D., McColl, E., Tincello, D. G., & Hilton, P. (2018) · Pilot and Feasibility Studies · doi:10.1186/s40814-018-0255-y · Cited by 11 · see citing works
Self-citation
The split-plot design was useful for evaluating complex, multilevel interventions, but there is need for improvement in its design and report
Goulão, B., MacLennan, G., & Ramsay, C. R. (2017) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2017.10.019 · Cited by 10 · see citing works
Self-citation
Correct reporting and interpretation of clinical data
Marks, M., & Rodrigues, J. N. (2017) · Journal of Hand Surgery (European Volume) · doi:10.1177/1753193417733154 · Cited by 10 · see citing works
Blinded sample size recalculation in clinical trials with binary composite endpoints
Sander, A., Rauch, G., & Kieser, M. (2016) · Journal of Biopharmaceutical Statistics · doi:10.1080/10543406.2016.1198371 · Cited by 9 · see citing works
A systematic review investigating the use of microbiology outcome measures in randomized controlled trials evaluating antimicrobial stewardship interventions published between 2011 and 2021
Lau, M., Daniel, R., Hughes, K., Wootton, M., Hood, K., & Gillespie, D. (2022) · JAC-Antimicrobial Resistance · doi:10.1093/jacamr/dlac013 · Cited by 9 · see citing works
Reporting and communication of sample size calculations in adaptive clinical trials: a review of trial protocols and grant applications
Zhang, Q., Dimairo, M., Julious, S. A., Lewis, J., & Yu, Z. (2024) · BMC Medical Research Methodology · doi:10.1186/s12874-024-02339-7 · Cited by 8 · see citing works
Clinical significance in pediatric oncology randomized controlled treatment trials: a systematic review
Howard, A. F., Goddard, K., Rassekh, S. R., Samargandi, O. A., & Hasan, H. (2018) · Trials · doi:10.1186/s13063-018-2925-8 · Cited by 8 · see citing works
Mortality trends in sickle cell patients.
Cintrón-García, J. J., Ajebo, G. H., Kota, V. K., & Guddati, A. K. (2020) · PubMed Central · Cited by 7 · see citing works
Protocol for a randomised controlled feasibility study examining the efficacy of brief cognitive therapy for the treatment of panic disorder in adolescents (PANDA)
Waite, P. (2022) · Pilot and Feasibility Studies · doi:10.1186/s40814-022-01009-z · Cited by 6 · see citing works
Colchicine for the primary prevention of cardiovascular events
Martí-Carvajal, A. J., Gemmato-Valecillos, M. A., Martín, D. M., Sanctis, J. B. D., Martí-Amarista, C. E., Hidalgo, R., Alegría‐Barrero, E., Lizardo, R. J. R., & Correa-Pérez, A. (2025) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015003.pub2 · Cited by 5 · see citing works
Current practice in methodology and reporting of the sample size calculation in randomised trials of hip and knee osteoarthritis: a protocol for a systematic review
Copsey, B. J., Dutton, S., Fitzpatrick, R. M., Lamb, S. E., & Cook, J. A. (2017) · Trials · doi:10.1186/s13063-017-2209-8 · Cited by 5 · see citing works
Self-citation
50 Tips for Clinical Trialists
Harvey, L. A., Glinsky, J. V., & Herbert, R. (2017) · Brain Impairment · doi:10.1017/brimp.2017.30 · Cited by 4 · see citing works
Using the benefit-harm trade-off method to determine the smallest worthwhile effect of intensive motor training on strength for people with spinal cord injury
Tranter, K. E., Glinsky, J. V., Ben, M., Patterson, H., Blecher, L., Chu, J., & Harvey, L. A. (2024) · Spinal Cord · doi:10.1038/s41393-024-00979-6 · Cited by 3 · see citing works
Do Patient Characteristics Matter When Calculating Sample Size for Eczema Clinical Trials?
Howells, L., Gran, S., Chalmers, J. R., Stuart, B. L., Santer, M., Bradshaw, L. E., Gaunt, D., Ridd, M. J., Gerbens, L. A. A., Spuls, P. I., et al. (2021) · Skin Health and Disease · doi:10.1002/ski2.42 · Cited by 3 · see citing works
The combination of physical activity and late-time-restricted eating improves eating behavior, cognitive performance and cardiovascular parameters in women living with excess body weight
Miladi, S., Hammouda, O., Trabelsi, S., Miladi, S. C., Ameur, R., & Driss, T. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.115200 · Cited by 2 · see citing works
Contributions of a survey and retrospective cohort study to the planning of a randomised controlled trial of corticosteroids in the treatment of paediatric septic shock
Liu, A., & Menon, K. (2018) · Trials · doi:10.1186/s13063-018-2664-x · Cited by 2 · see citing works
Basic Design Considerations
Machin, D., Campbell, M. J., Tan, S. B., & Tan, S. H. (2018) · doi:10.1002/9781118874905.ch1 · Cited by 2 · see citing works
Effect of high-dose glucocorticoids on persistent opioid use 3 to 12 months after primary total hip or knee arthroplasty. Protocol for a target trial emulation using observational data from Danish registriesPreprint
Laigaard, J., Christensen, R., Varnum, C., Lindberg‐Larsen, M., Lunn, T. H., Mathiesen, O., & Overgaard, S. (2023) · medRxiv · doi:10.1101/2023.10.31.23297517 · Cited by 2 · see citing works
External Validation of the Minimal Clinically Important Difference of FeNO Using the Asthma Control Questionnaire
Noble, J., Bean, O., Sayers, R., Cullen, R., Beasley, R. W., & Weatherall, M. (2025) · Clinical & Experimental Allergy · doi:10.1111/cea.70131 · Cited by 1 · see citing works
Effectiveness of guided endodontic microsurgery using a trephine bur in critical anatomical regions: a randomized controlled clinical trial
Kaddoura, R., Lazkani, T., & Tolibah, Y. A. (2026) · BDJ Open · doi:10.1038/s41405-026-00461-w · Cited by 1 · see citing works
A protocol for the conduct of a multicentre, prospective, randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures
Franssen, M., Achten, J., Appelbe, D., Costa, M. L., Dutton, S., Mason, J. M., Gould, J., Gray, A. R., Rangan, A., Sheehan, W., et al. (2024) · Bone & Joint Open · doi:10.1302/2633-1462.54.bjo-2023-0151.r1 · Cited by 1 · see citing works
Beyond statistical power in designing clinical trials: Shiny/R apps to the rescue
Sandoval, P., Vilaprinyó, E., Alves, R., & Albert Sorribas, B. (2025) · Teaching Statistics · doi:10.1111/test.12403 · Cited by 1 · see citing works
High-dose glucocorticoids, pain, and adverse events. Protocol for an analysis of a natural experiment of patients undergoing hip and knee arthroplastyPreprint
Laigaard, J., Møller, M. Ø., Overgaard, S., Mathiesen, O., & Karlsen, A. P. H. (2025) · medRxiv · doi:10.1101/2025.11.11.25339982 · Cited by 1 · see citing works
Editorial. Choices in clinical trial design
Carter, B. S., & Barker, F. G. (2019) · Journal of neurosurgery · doi:10.3171/2019.7.jns183276
Choosing the Target Difference (“effect size”) for a Randomised Controlled Trial - DELTA2 GuidancePreprint
Cook, J. A., Julious, S. A., Sones, W. R., Hampson, L. V., Hewitt, C. E., Berlin, J. A., Ashby, D., Emsley, R., Fergusson, D. A., Walters, S. J., et al. (2018) · Preprints.org · doi:10.20944/preprints201808.0521.v1
Self-citation
Cumulative References
Machin, D., Campbell, M. J., Tan, S. B., & Tan, S. H. (2018) · Wiley eBooks · doi:10.1002/9781118874905.refs
Empirical and Translational Pilots
Reynolds, P. S. (2023) · Wiley eBooks · doi:10.1002/9781119800002.ch6
Deciding the Appropriate Sample Size for Clinical Trials: A complex interplay between power, effect size, and costPreprint
Sandoval, P., Vilaprinyó, E., Alves, R., & Albert Sorribas, B. (2024) · Research Square · doi:10.21203/rs.3.rs-4728662/v1 · Cited by 1 · see citing works
Additional file 1 of Reporting and communication of sample size calculations in adaptive clinical trials: a review of trial protocols and grant applications
Zhang, Q., Dimairo, M., Julious, S. A., Lewis, J., & Yu, Z. (2024) · Figshare · doi:10.6084/m9.figshare.27124117
Refined trial sequential analysis for meta-analyses with few studies
Wang, Y., & Lin, L. (2026) · Journal of the Royal Statistical Society Series C (Applied Statistics) · doi:10.1093/jrsssc/qlag050

Choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial – the development of the DELTA2 guidance
Sones, W. R., Julious, S. A., Rothwell, J. C., Ramsay, C. R., Hampson, L. V., Emsley, R., Walters, S. J., Hewitt, C. E., Bland, M., Fergusson, D. A., et al. (2018) · Trials · doi:10.1186/s13063-018-2887-x · Cited by 13 · see citing works
Self-citation
Choosing the target difference (‘effect size’) for a randomised controlled trial - DELTA2 guidance protocol
Cook, J. A., Julious, S. A., Sones, W. R., Rothwell, J. C., Ramsay, C. R., Hampson, L. V., Emsley, R., Walters, S. J., Hewitt, C. E., Bland, M., et al. (2017) · Trials · doi:10.1186/s13063-017-1969-5 · Cited by 14 · see citing works
Self-citation
DELTA2 guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial
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., et al. (2018) · Trials · doi:10.1186/s13063-018-2884-0 · Cited by 197 · see citing works
Self-citation
DELTA2 guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial Suzie Cro
Cook, J. A., Julious, S. A., Sones, W., Hampson, L., Hewitt, C., Berlin, J. A., Ashby, D., Emsley, R., Fergusson, D. A., Walters, S. J., et al. (2018) · Lancaster EPrints (Lancaster University)
Self-citation
Assessing methods to specify the target difference for a randomised controlled trial: DELTA (Difference ELicitation in TriAls) review
Cook, J., Hislop, J., Adewuyi, T., Harrild, K., Altman, D., Ramsay, C., Fraser, C., Buckley, B., Fayers, P., Harvey, I., et al. (2014) · Health Technology Assessment · doi:10.3310/hta18280 · Cited by 194 · see citing works
Self-citation

Authors: Cook, J. A., Hislop, J., Altman, D. G., Fayers, P., Briggs, A. H., Ramsay, C. R., Norrie, J. D., Harvey, I. M., Buckley, B., Fergusson, D., Ford, I., Vale, L. D., & for the DELTA group
Affiliations: University of Aberdeen (GB)
Newcastle University (GB)
Nuffield Orthopaedic Centre (GB)
University of Glasgow (GB)
University of East Anglia (GB)
National University of Ireland (IE)
Ottawa Hospital Research Institute (CA)
Corresponding author: Cook, Jonathan A
ORCID: Cook, Jonathan A
Altman, Douglas G
Fayers, Peter
Briggs, Andrew H
Ramsay, Craig R
Norrie, John D
Buckley, Brian
Fergusson, Dean
Ford, Ian
Vale, Luke D
Venue: Trials
Publisher: Springer Science and Business Media LLC
Published: 2015-01-15
Volume: 16
Issue: 1
Pages: 12-12
ISSN: 1745-6215 (ISSN-L)
DOI: 10.1186/s13063-014-0526-8
PMC: PMC4302137
OpenAlex: W2136396870
Cited by: 66
References: 41
Citations by year: 2026: 2 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 19 · 2017: 7 · 2016: 5 · 2015: 1
FWCI: 9.49
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Trials (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
Aberdeen University Research Archive (Aberdeen University) (submittedVersion, cc-by)
uO Research (University of Ottawa) (submittedVersion, public-domain)
Arrow@dit (Dublin Institute of Technology) (submittedVersion)
ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders: Scottish Government
Cancer Research UK (16895)
National Institute for Health and Care Research (NF-SI-0513-10131)
University of Aberdeen (G1002292)
Chief Scientist Office, Scottish Government Health and Social Care Directorate
Medical Research Council (G0601938, MR/K02325X/1, G1002292)
NIHR Evaluation Trials and Studies Coordinating Centre
Topics: Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords: sample size determination, primary outcomes, randomized controlled trial design, statistical power, superiority trials, trial protocol reporting, DELTA project
MeSH terms: Data Interpretation, Statistical, Humans, Randomized Controlled Trials as Topic, Treatment Outcome, Practice Guidelines as Topic, Sample Size, Endpoint Determination

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Specifying the target difference in the primary outcome for a randomised controlled trial: guidance for researchers

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks