The DOI matches its Crossref record; 28 of the 29 references it cites were found in a registry or an index.
Methodology of superiority vs. equivalence trials and non-inferiority trials
Abstract
The randomized clinical trial (RCT) is generally accepted as the best method of comparing effects of therapies. Most often the aim of an RCT is to show that a new therapy is superior to an established therapy or placebo, i.e. they are planned and performed as superiority trials. Sometimes the aim of an RCT is just to show that a new therapy is not superior but equivalent to or not inferior to an established therapy, i.e. they are planned and performed as equivalence trials or non-inferiority trials. Since the types of trials have different aims, they differ significantly in various methodological aspects. The awareness of the methodological differences is generally quite limited. This paper reviews the methodology of these types of trials with special reference to differences in respect to planning, performance, analysis and reporting of the trial. In this context the relevant basal statistical concepts are reviewed. Some of the important points are illustrated by examples.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“All but one of the trials were powered to test superiority, not equivalence or non-inferiority41, so it would be premature to construe our findings as proof of equivalent effects.”
From The effectiveness of virtual reality based interventions for symptoms of anxiety and depression: A meta-analysis (2018) · cites this paper as [41]
Citations
Cites
Moher, D., Schulz, K. F., & Altman, D. G. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04337-3 · Cited by 5,373
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
Assessing the quality of controlled clinical trials
Jüni, P., Altman, D. G., & Egger, M. (2001) · BMJ · doi:10.1136/bmj.323.7303.42 · Cited by 3,309 · cited 1×
“To ensure the best possible quality of the analysis it is important to collect complete follow-up data on all randomized patients as per protocol, irrespective of whether they are subsequently found to have failed entry criteria, withdraw from trial medication prematurely, or violate the protocol in some other way [20…”
BackgroundImproving the Quality of Reporting of Randomized Controlled Trials: The CONSORT Statement
Begg, C. (1996) · JAMA · doi:10.1001/jama.1996.03540080059030 · Cited by 3,127
Clinical Trials: A Practical Approach.
Hill, I. D., & Pocock, S. (1984) · Biometrics · doi:10.2307/2531186 · Cited by 2,918
Moher, D., Schulz, K. F., & Altman, D. G. (2001) · BMC Medical Research Methodology · doi:10.1186/1471-2288-1-2 · Cited by 2,755
Piaggio, G., Elbourne, D. R., Pocock, S. J., Evans, S. J. W., Altman, D. G., & CONSORT Group, F. T. (2012) · JAMA · doi:10.1001/jama.2012.87802 · Cited by 2,428
Chan, A.-W., Hróbjartsson, A., Haahr, M. T., Gøtzsche, P. C., & Altman, D. G. (2004) · JAMA · doi:10.1001/jama.291.20.2457 · Cited by 1,845
Reporting of Noninferiority and Equivalence Randomized Trials: An Extension of the CONSORT Statement
Piaggio, G., Elbourne, D. R., Altman, D. G., Pocock, S. J., Evans, S. J. W., & CONSORT Group, F. T. (2006) · JAMA · doi:10.1001/jama.295.10.1152 · Cited by 1,153
Trials to assess equivalence: the importance of rigorous methods: Fig 1
Jones, B., Jarvis, P., Lewis, J. A., & Ebbutt, A. F. (1996) · BMJ · doi:10.1136/bmj.313.7048.36 · Cited by 1,032
“Proving the null hypothesis” in clinical trials
Blackwelder, W. C. (1982) · Controlled Clinical Trials · doi:10.1016/0197-2456(82)90024-1 · Cited by 890
Statistical Power, Sample Size, and Their Reporting in Randomized Controlled Trials
Moher, D. (1994) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1994.03520020048013 · Cited by 608
Quality of Reporting of Noninferiority and Equivalence Randomized Trials
Le Henanff, A., Giraudeau, B., Baron, G., & Ravaud, P. (2006) · JAMA · doi:10.1001/jama.295.10.1147 · Cited by 263
Statistical Methods in Medical Research.
Armitage, P., & Berry, G. (1997) · Biometrics · doi:10.2307/2533132 · Cited by 260
Bartko, J. J. (1991) · American Psychologist · doi:10.1037/0003-066x.46.10.1089.a · Cited by 250
Sample size requirements for evaluating a conservative therapy.
Makuch, R., & Simon, R. M. (1978) · PubMed · Cited by 231
Detsky, A. S. (1985) · Archives of Internal Medicine · doi:10.1001/archinte.145.4.709 · Cited by 228
Claims of Equivalence in Medical Research: Are They Supported by the Evidence?
Greene, W. L., Concato, J., & Feinstein, A. R. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-9-200005020-00006 · Cited by 180
Faller, H. (2004) · Die Rehabilitation · doi:10.1055/s-2004-818553 · Cited by 167
Choosing an equivalence limit for noninferiority or equivalence studies
Wiens, B. L. (2002) · Controlled Clinical Trials · doi:10.1016/s0197-2456(01)00196-9 · Cited by 164
Lange, S., & Freitag, G. (2005) · Biometrical Journal · doi:10.1002/bimj.200410085 · Cited by 111
Negative Results of Randomized Clinical Trials Published in the Surgical Literature
Dimick, J. B., Diener‐West, M., & Lipsett, P. A. (2001) · Archives of Surgery · doi:10.1001/archsurg.136.7.796 · Cited by 96
Planning and Monitoring of Equivalence Studies
Durrleman, S., & Simon, R. (1990) · Biometrics · doi:10.2307/2531438 · Cited by 96
Therapeutic equivalence: fallacies and falsification
Garrett, A. D. (2003) · Statistics in Medicine · doi:10.1002/sim.1360 · Cited by 88
Scientific and Ethical Issues in Equivalence Trials
Djulbegović, B. (2001) · JAMA · doi:10.1001/jama.285.9.1206 · Cited by 79
General design issues in efficacy, equivalency and superiority trials
Fleiss, J. L. (1992) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.1992.tb01684.x · Cited by 49
Negative results in cancer clinical trials—equivalence or poor accrual?
Costa, L. J., Xavier, A. C., & del Giglio, A. (2004) · Controlled Clinical Trials · doi:10.1016/j.cct.2004.08.001 · Cited by 21
Research works printed but not linked: 1
- Lange, 2005, Choice of delta: requirements and reality – results of a systematic review, Biomed J, 47, 12
Cited by
Sorted by citations
Machine learning for medical imaging: methodological failures and recommendations for the future
Varoquaux, G. P., & Cheplygina, V. (2022) · npj Digital Medicine · doi:10.1038/s41746-022-00592-y · Cited by 815
Sample size calculations: basic principles and common pitfalls
Noordzij, M., Tripepi, G. L., Dekker, F. W., Zoccali, C., Tanck, M. W. T., & Jager, K. J. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp732 · Cited by 440
Fodor, L. A., Coteț, C. D., Cuijpers, P., Szamoskozi, Ș., David, D., & Cristea, I. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-28113-6 · Cited by 284
Samano, N., Geijer, H., Lidén, M., Fremes, S. E., Bodin, L., & Souza, D. S. R. (2015) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2015.07.027 · Cited by 299
Intention to treat and per protocol analysis in clinical trials
Tripepi, G., Chesnaye, N. C., Dekker, F. W., Zoccali, C., & Jager, K. J. (2020) · Nephrology · doi:10.1111/nep.13709 · Cited by 284
Metadata
- Authors
- Christensen, E.
- Affiliations
- Bispebjerg Hospital (DK)
- Corresponding author
- Christensen, Erik
- ORCID
- Christensen, Erik
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 46
- Issue
- 5
- Pages
- 947-954
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2018758420
- Cited by
- 205
- References
- 29
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 16 · 2023: 19 · 2022: 12 · 2021: 6 · 2020: 14 · 2019: 13 · 2018: 14 · 2017: 15 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 11 · 2012: 5
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- superiority trials, equivalence trials, randomized controlled trials, trial design, statistical analysis, trial reporting, statistical concepts, treatment comparison
- MeSH terms
- Animals, Clinical Protocols, Clinical Trials as Topic, Data Interpretation, Statistical, Humans, Patient Compliance, Research Design, Therapeutic Equivalency, Confidence Intervals, Randomized Controlled Trials as Topic, Sample Size, Risk Assessment
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
