The Choice of Priorities in Contemporary Comparative Trials: Superiority vs non Inferiority. Causes and Effects
https://doi.org/10.18087/cardio.2020.10.n1288
Abstract
The article compares two statistical approaches, which are commonly used in current comparative studies, a hypothesis that a drug is superior over another one (superiority) and a hypothesis that a drug is not inferior to another one in the efficacy and safety (non-inferiority). Using the example of specific studies, the difference between the methods and the tasks, for the solution of which one or another method should be applied, are shown. In order to prove the superiority in efficacy and safety of a new drug over an existing one, only a statistical approach that uses the “superiority” hypothesis is applicable. Studies using the “non-inferiority” hypothesis are generally used for comparing drugs, which are not considerably different in their efficacy, but the study drug has other advantages in the administration, storage, tolerability etc. The choice of statistical method is determined exclusively by the task of the study.
Keywords
"Superiority" statistical hypothesis,
"non-inferiority" statistical hypothesis,
apixaban,
rivaroxaban,
dabigatran
Supporting agencies: The publication was supported by the company Pfizer. The article expresses the authors’ position, which may be different from the position of the company Pfizer.
About the Authors
F. T. Ageev
Institute of Clinical Cardiology. A.L. Myasnikova "National Medical Research Center of Cardiology of the Ministry of Health of Russia, Moscow
Russian Federation
Professor, Doctor of Medical Sciences, Chief Researcher of the Department of Outpatient Treatment and Diagnostic Technologies of the National Medical Research Center of Cardiology
Russian Federation
Professor, Doctor of Medical Sciences, Chief Researcher of the Department of Outpatient Treatment and Diagnostic Technologies of the National Medical Research Center of Cardiology
E. B. Yarovaya
Moscow State University M.V. Lomonosov, Moscow
Consultative and diagnostic department, MD, PhD
Consultative and diagnostic department, MD, PhD
References
1. Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial – the Losartan Heart Failure Survival Study ELITE II. Lancet (London, England). 2000;355(9215):1582–7. PMID: 10821361
2. Schumi J, Wittes JT. Through the looking glass: understanding non-inferiority. Trials. 2011;12(1):106. DOI: 10.1186/1745-6215-12-106
3. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al. Dabigatran versus warfarin in patients with atrial fibrillation. New England Journal of Medicine. 2009;361(12):1139–51. DOI: 10.1056/NEJMoa0905561
4. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New England Journal of Medicine. 2011;365(10):883–91. DOI: 10.1056/NEJMoa1009638
5. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M et al. Apixaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine. 2011;365(11):981–92. DOI: 10.1056/NEJMoa1107039
6. Graham DJ, Baro E, Zhang R, Liao J, Wernecke M, Reichman ME et al. Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation. The American Journal of Medicine. 2019;132(5):596-604. e11. DOI: 10.1016/j.amjmed.2018.12.023
7. Martinez BK, Bunz TJ, Eriksson D, Meinecke A-K, Sood NA, Coleman CI. Effectiveness and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and heart failure. ESC Heart Failure. 2019;6(1):10–5. DOI: 10.1002/ehf2.12365
8. Diener H-C, Aisenberg J, Ansell J, Atar D, Breithardt G, Eikelboom J et al. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. European Heart Journal. 2016;38(12):860–8. DOI: 10.1093/eurheartj/ehw069
9. Pazan F, Collins R, Gil VM, Hanon O, Hardt R, Hoffmeister M et al. A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019). Drugs & Aging. 2020;37(7):539–48. DOI: 10.1007/s40266-020-00771-0
10. Culebras A, Messe SR, Chaturvedi S, Kase CS, Gronseth G. Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(8):716–24. DOI: 10.1212/WNL.0000000000000145
11. Abraham NS, Noseworthy PA, Yao X, Sangaralingham LR, Shah ND. Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study. Gastroenterology. 2017;152(5):1014-1022.e1. DOI: 10.1053/j.gastro.2016.12.018
12. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. New England Journal of Medicine. 2020;382(17):1599–607. DOI: 10.1056/NEJMoa1915103
Review
For citations:
Ageev F.T., Yarovaya E.B. The Choice of Priorities in Contemporary Comparative Trials: Superiority vs non Inferiority. Causes and Effects. Kardiologiia. 2020;60(10):107-112. (In Russ.) https://doi.org/10.18087/cardio.2020.10.n1288
Views:
10262
Email this article 
Post a Comment 
