Skip to main content
Top
Published in: Journal of General Internal Medicine 2/2011

01-02-2011 | Reviews

Understanding Equivalence and Noninferiority Testing

Authors: Esteban Walker, PhD, Amy S. Nowacki, PhD

Published in: Journal of General Internal Medicine | Issue 2/2011

Login to get access

Abstract

Increasingly, the goal of many studies is to determine if new therapies have equivalent or noninferior efficacies to the ones currently in use. These studies are called equivalence/noninferiority studies, and the statistical methods for their analysis require only simple modifications to the traditional hypotheses testing framework. Nevertheless, important and subtle issues arise with the application of such methods. This article describes the concepts and statistical methods involved in testing equivalence/noninferiority. The aim is to enable the clinician to understand and critically assess the growing number of articles utilizing such methods.
Literature
1.
go back to reference Staszewski S, Keisser P, Montaner J, et al. Abacavir-Lamivudine-Zidobudine vs Indinavir-Lamivudine-Zidobudine in antiretroviral-naïve HIV-infected adults. JAMA. 2001;285:1155–1163.CrossRefPubMed Staszewski S, Keisser P, Montaner J, et al. Abacavir-Lamivudine-Zidobudine vs Indinavir-Lamivudine-Zidobudine in antiretroviral-naïve HIV-infected adults. JAMA. 2001;285:1155–1163.CrossRefPubMed
2.
go back to reference Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing equivalence of average bioavailability. J Pharmacokin Biopharm. 1987;15:657–680.CrossRef Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing equivalence of average bioavailability. J Pharmacokin Biopharm. 1987;15:657–680.CrossRef
3.
go back to reference Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators (OASIS-5). Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354:1464–76.CrossRef Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators (OASIS-5). Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354:1464–76.CrossRef
4.
go back to reference Wellek S. Testing Statistical Hypotheses of Equivalence. Boca Raton, FL: Chapman & Hall; 2003. Wellek S. Testing Statistical Hypotheses of Equivalence. Boca Raton, FL: Chapman & Hall; 2003.
5.
go back to reference Garret AD. Therapeutic equivalence: fallacies and falsification. Statist Med. 2003;22:741–762.CrossRef Garret AD. Therapeutic equivalence: fallacies and falsification. Statist Med. 2003;22:741–762.CrossRef
6.
go back to reference Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med. 2006;145:62–69.PubMed Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med. 2006;145:62–69.PubMed
7.
go back to reference Barker LE, Luman ET, McCauley MM, Chu SY. assessing equivalence: an alternative to the use of difference tests for measuring disparities in vaccination coverage. Am J Epidemiol. 2002;156:1056–1061.CrossRefPubMed Barker LE, Luman ET, McCauley MM, Chu SY. assessing equivalence: an alternative to the use of difference tests for measuring disparities in vaccination coverage. Am J Epidemiol. 2002;156:1056–1061.CrossRefPubMed
9.
go back to reference Wiens BL, Zhao W. The role of intention to treat in analysis of noninferiority studies. Clinical Trials. 2007;4:286–291.CrossRefPubMed Wiens BL, Zhao W. The role of intention to treat in analysis of noninferiority studies. Clinical Trials. 2007;4:286–291.CrossRefPubMed
10.
go back to reference Ebbutt AF, Frith L. Practical issues in equivalence trials. Statist Med. 1998;17:1691–1701.CrossRef Ebbutt AF, Frith L. Practical issues in equivalence trials. Statist Med. 1998;17:1691–1701.CrossRef
12.
go back to reference Ellenberg SS, Temple R. Placebo-controlled trials and active-control trials in the evaluation of new treatments: part 2: practical issues and specific cases. Ann Intern Med. 2000;133:464–470.PubMed Ellenberg SS, Temple R. Placebo-controlled trials and active-control trials in the evaluation of new treatments: part 2: practical issues and specific cases. Ann Intern Med. 2000;133:464–470.PubMed
13.
go back to reference Temple R, Ellenberg SS. Placebo-controlled trials and active-control trials in the evaluation of new treatments: part 1: ethical and scientific issues. Ann Intern Med. 2000;133:455–453.PubMed Temple R, Ellenberg SS. Placebo-controlled trials and active-control trials in the evaluation of new treatments: part 1: ethical and scientific issues. Ann Intern Med. 2000;133:455–453.PubMed
14.
go back to reference Le Henanff A, Girardeau B, Baron G, et al. Quality of reporting of noninferiority and equivalence randomized trials. JAMA. 2006;295:1147–1151.CrossRefPubMed Le Henanff A, Girardeau B, Baron G, et al. Quality of reporting of noninferiority and equivalence randomized trials. JAMA. 2006;295:1147–1151.CrossRefPubMed
15.
go back to reference Gotzsche PC. Lessons from and cautions about noninferiority and equivalence random trials. JAMA. 2006;295:1172–74.CrossRefPubMed Gotzsche PC. Lessons from and cautions about noninferiority and equivalence random trials. JAMA. 2006;295:1172–74.CrossRefPubMed
16.
go back to reference Piaggio G, Elbourne DR, Altman DG, et al. Reporting of noninferiority and equivalence randomized trials. An extension of the CONSORT statement. JAMA. 2006;295:1152–1160.CrossRefPubMed Piaggio G, Elbourne DR, Altman DG, et al. Reporting of noninferiority and equivalence randomized trials. An extension of the CONSORT statement. JAMA. 2006;295:1152–1160.CrossRefPubMed
Metadata
Title
Understanding Equivalence and Noninferiority Testing
Authors
Esteban Walker, PhD
Amy S. Nowacki, PhD
Publication date
01-02-2011
Publisher
Springer-Verlag
Published in
Journal of General Internal Medicine / Issue 2/2011
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-010-1513-8

Other articles of this Issue 2/2011

Journal of General Internal Medicine 2/2011 Go to the issue

Clinical Practice: Clinical Images

Concurrent Sweet’s Syndrome and Erythema Nodosum

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.