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01-07-2020 | Research and Reporting Methods

Including Non-inferiority Trials in Contemporary Meta-analyses of Chronic Medical Conditions: a Meta-epidemiological Study

Authors: Zhen Wang, PhD, Tarek Nayfeh, MD, Nigar Sofiyeva, MD, MS, Oscar J. Ponte, MD, Rami Rajjoub, Konstantinos Malandris, MD, Mohamed Seisa, MD, Haitao Chu, PhD, MD, Mohammad Hassan Murad, MD, MPH

Published in: Journal of General Internal Medicine | Issue 7/2020

Excerpt

Randomized controlled trials (RCTs) have historically addressed whether one treatment is superior to another. Therefore, their null hypothesis was that no statistically significant difference exists between the two treatments. In recent years, another type of RCTs, non-inferiority trials (NITs), has become prevalent in the medical literature.^1‐4 Contrary to superiority trials, NITs try to answer whether a treatment is no worse than the control treatment by a predefined non-inferiority margin. The null hypothesis of NITs is that the treatment is worse than the control by more than the non-inferiority margin; rejecting the null hypothesis means the treatment is not inferior to the control (i.e., the treatment is at least as good as the control). …

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Bikdeli B, Welsh JW, Akram Y, Punnanithinont N, Lee I, Desai NR, et al. Noninferiority Designed Cardiovascular Trials in Highest-Impact Journals. Circulation. 2019;140(5):379-89. https://doi.org/10.1161/CIRCULATIONAHA.119.040214 CrossRefPubMed

Suda KJ, Hurley AM, McKibbin T, Motl Moroney SE. Publication of noninferiority clinical trials: changes over a 20-year interval. Pharmacotherapy. 2011;31(9):833-9. https://doi.org/10.1592/phco.31.9.833 CrossRefPubMed

Murthy VL, Desai NR, Vora A, Bhatt DL. Increasing proportion of clinical trials using noninferiority end points. Clin Cardiol. 2012;35(9):522-3. https://doi.org/10.1002/clc.22040 CrossRefPubMedPubMedCentral

Mauri L, D'Agostino RB, Sr. Challenges in the Design and Interpretation of Noninferiority Trials. N Engl J Med. 2017;377(14):1357-67. https://doi.org/10.1056/NEJMra1510063 CrossRefPubMed

Garattini S, Bertele V. Non-inferiority trials are unethical because they disregard patients' interests. Lancet. 2007;370(9602):1875-7. https://doi.org/10.1016/S0140-6736(07)61604-3 CrossRefPubMed

Head SJ, Kaul S, Bogers AJ, Kappetein AP. Non-inferiority study design: lessons to be learned from cardiovascular trials. Eur Heart J. 2012;33(11):1318-24. https://doi.org/10.1093/eurheartj/ehs099 CrossRefPubMed

Kaul S, Diamond GA, Weintraub WS. Trials and tribulations of non-inferiority: the ximelagatran experience. J Am Coll Cardiol. 2005;46(11):1986-95. https://doi.org/10.1016/j.jacc.2005.07.062 CrossRefPubMed

United States Government Accountability Office. New Drug Approval FDA’s Consideration of Evidence from Certain Clinical Trial. 2010.

Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med. 2006;145(1):62-9. https://doi.org/10.7326/0003-4819-145-1-200607040-00011 CrossRefPubMed

10.

James Hung HM, Wang SJ, Tsong Y, Lawrence J, O'Neil RT. Some fundamental issues with non-inferiority testing in active controlled trials. Stat Med. 2003;22(2):213-25. https://doi.org/10.1002/sim.1315 CrossRefPubMed

11.

Hung HM, Wang SJ, O'Neill R. A regulatory perspective on choice of margin and statistical inference issue in non-inferiority trials. Biom J. 2005;47(1):28-36; discussion 99-107.CrossRef

12.

D'Agostino RB, Sr., Massaro JM, Sullivan LM. Non-inferiority trials: design concepts and issues - the encounters of academic consultants in statistics. Stat Med. 2003;22(2):169-86. https://doi.org/10.1002/sim.1425 CrossRefPubMed

13.

Snapinn SM. Alternatives for discounting in the analysis of noninferiority trials. J Biopharm Stat. 2004;14(2):263-73. https://doi.org/10.1081/BIP-120037178 CrossRefPubMed

14.

Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to assess equivalence: the importance of rigorous methods. BMJ. 1996;313(7048):36-9. https://doi.org/10.1136/bmj.313.7048.36 CrossRefPubMedPubMedCentral

15.

Althunian TA, de Boer A, Klungel OH, Insani WN, Groenwold RH. Methods of defining the non-inferiority margin in randomized, double-blind controlled trials: a systematic review. Trials. 2017;18(1):107. https://doi.org/10.1186/s13063-017-1859-x CrossRefPubMedPubMedCentral

16.

Gotzsche PC. Lessons from and cautions about noninferiority and equivalence randomized trials. JAMA. 2006;295(10):1172-4. https://doi.org/10.1001/jama.295.10.1172 CrossRefPubMed

17.

Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG, Group C. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA. 2012;308(24):2594-604. https://doi.org/10.1001/jama.2012.87802 CrossRefPubMed

18.

Rehal S, Morris TP, Fielding K, Carpenter JR, Phillips PP. Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals. BMJ Open. 2016;6(10):e012594. https://doi.org/10.1136/bmjopen-2016-012594 CrossRefPubMedPubMedCentral

19.

Murad MH, Wang Z. Guidelines for reporting meta-epidemiological methodology research. Evid Based Med. 2017;22(4):139-42. https://doi.org/10.1136/ebmed-2017-110713 CrossRefPubMedPubMedCentral

20.

Alahdab F, Farah W, Almasri J, Barrionuevo P, Zaiem F, Benkhadra R, et al. Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study. Mayo Clin Proc. 2018;93(3):278-83. https://doi.org/10.1016/j.mayocp.2017.10.020 CrossRefPubMed

21.

Parekh AK, Goodman RA, Gordon C, Koh HK, Conditions HHSIWoMC. Managing multiple chronic conditions: a strategic framework for improving health outcomes and quality of life. Public Health Rep. 2011;126(4):460-71. https://doi.org/10.1177/003335491112600403 CrossRefPubMedPubMedCentral

22.

Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815-34. https://doi.org/10.1002/(sici)1097-0258(19981230)17:24<2815::aid-sim110>3.0.co;2-8 CrossRefPubMed

23.

Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. 2nd ed. Hoboken: J. Wiley; 2002.CrossRef

24.

Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326(7382):219. https://doi.org/10.1136/bmj.326.7382.219 CrossRefPubMedPubMedCentral

25.

Rover C, Knapp G, Friede T. Hartung-Knapp-Sidik-Jonkman approach and its modification for random-effects meta-analysis with few studies. BMC Med Res Methodol. 2015;15:99. https://doi.org/10.1186/s12874-015-0091-1 CrossRefPubMedPubMedCentral

26.

Veroniki AA, Jackson D, Bender R, Kuss O, Langan D, Higgins JPT, et al. Methods to calculate uncertainty in the estimated overall effect size from a random-effects meta-analysis. Res Synth Methods. 2019;10(1):23-43. https://doi.org/10.1002/jrsm.1319 CrossRefPubMed

27.

Zhang XL, Zhu L, Wei ZH, Zhu QQ, Qiao JZ, Dai Q, et al. Comparative Efficacy and Safety of Everolimus-Eluting Bioresorbable Scaffold Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis. Ann Intern Med. 2016;164(11):752-63. https://doi.org/10.7326/M16-0006 CrossRefPubMed

28.

Cassese S, Byrne RA, Ndrepepa G, Kufner S, Wiebe J, Repp J, et al. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387(10018):537-44. https://doi.org/10.1016/S0140-6736(15)00979-4 CrossRefPubMed

Title: Including Non-inferiority Trials in Contemporary Meta-analyses of Chronic Medical Conditions: a Meta-epidemiological Study
Authors: Zhen Wang, PhD
Tarek Nayfeh, MD
Nigar Sofiyeva, MD, MS
Oscar J. Ponte, MD
Rami Rajjoub
Konstantinos Malandris, MD
Mohamed Seisa, MD
Haitao Chu, PhD, MD
Mohammad Hassan Murad, MD, MPH
Publication date: 01-07-2020
Publisher: Springer International Publishing
Published in: Journal of General Internal Medicine / Issue 7/2020
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI: https://doi.org/10.1007/s11606-020-05821-2

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