REMEDIUMREMEDIUM1561-59362658-3534Joint-Stock Company Chicot105410.21518/1561-5936-2019-3-40-47Original ArticleProperties of the two one-sided tests procedure for the bioequivalence assessment of medicinal productsDranitsynaM. A.noemail@neicon.ruZakharovaT. V.noemail@neicon.ruNiyazovR. R.noemail@neicon.ruCenter for Scientific Advice LLCFederal State Budgetary Educational Institution of Higher Education Lomonosov Moscow State UniversityInstitute of Informatics Problems of the Russian Academy of SciencesFederal Research Center Informatics and Management of the Russian Academy of SciencesKorean Institute of Medical Industry Development031220193404718032022Copyright © 2019,2019In this paper, an overview of the decision-making rules and two one-sided tests procedure when assessing bioequivalence is provided. This includes a discussion of how the type I error is controlled, i.e. the way how the patient risks arising from the inherent uncertainty of statistical inferences are handled. Additionally, certain weaknesses of the current approach for the bioequivalence assessment are discussed.bioequivalencetype I errorstatistical testбиоэквивалентностьошибка I родастатистический критерий[CFR320.23 https://www.accessdata.fda.gov/scripts/cdrh/ cfdocs/cfcfr/CFRSearch.cfm?fr=320.23.][Информационный справочник понятий, применяемых в рамках Евразийского экономического союза в сфере обращения лекарственных средств http://eec.eaeunion.org/ru/act/texnreg/ deptexreg/LS1/Pages/pharm_glossary.aspx, доступ 01.11.2018.][EMA Guideline on the investigation of bioequivalence, 2010.][Shein-Chung Chow, Jen-pei Liu, Design and Analysis of Bioavailability and Bioequivalence Studies, Third Edition, by Taylor & Francis Group, LLC, 2009.][Schuirmann D.J. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval. Biometrics. 1981;37:617.][Schuirmann D.J. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceutics, 1987, 15, 657-680.][Davit B.M., Nwakama P.E., Buehler G.J., Conner D.P., Haidar S.H., Patel D.T., et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother. 2009;43(10):1583-97. Epub 2009/09/25. doi: 10.1345/aph.1M141.][Ивченко Г.И., Медведев Ю.И. Математическая статистика, Учеб. пособие для втузов. М.: Высш. шк., 1984. 248 стр.][Ennis J.M. & Ennis D.M. Equivalence hypothesis testing. Food Quality and Preference. 2010;21:253-256.][Berger R.L. & Hsu J.C. Rejoinder. Statistical Science. 1996b;11(4):315-319.][Kendall M.G. and Stuart A. The Advance Theory of Statistics. Vol. II, Griffen, London, UK, 1979.][Hsu J.C., Hwang J.T.G., Liu H.K. and Ruberg S.J. Confidence intervals associated with tests for bioequivalence. Biometrika. 1994;81:103-114.][Lehmann E.L. and Romano J.P. Testing Statistical Hypotheses. Springer, New York, 2005.][Hauschke D., Steinijans V.W. and Diletti E. A distribution-free procedure for the statistical analyses of bioequivalence studies. International Journal of Clinical Pharmacology, Therapy and Toxicology. 1990;28:72-78.][Labes D., Schutz H. Inflation of Type I Error in the Evaluation of Scaled Average Bioequivalence, and a Method for its Control. Pharm Res. 2017;33(11):2805-14.][Ромодановский Д.П., Горячев Д.В., Хохлов А.Л., Мирошников А.Е., Шитова А.М., Еременко Н.Н. «Patients risk» при проведении исследований биоэквивалентности высоковариабельных лекарственных препаратов. Медицинская этика. 2018;6(1):26-32.][Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, 38th ed. U. S. Food and Drug Administration 2018. URL: https://www.fda.gov/downloads/Drugs/ DevelopmentApprovalProcess/UCM071436.pdf.][Bate R., Mathur A., Lever H.M., Thakur D., Graedon J., Cooperman T., Mason P., Fox E.R. Generics Substitution, Bioequivalence Standards, and International Oversight: Complex Issues Facing the FDA. Trends Pharmacol Sci. 2016;37(3):184-191. doi:10.1016/j.tips.2015.11.005.][Corinne Seng Yue, Deniz Ozdin, Susannah Selber-Hnatiw, Murray Ducharme, Opportunities and Challenges Related to the Implementation of Model-Based Bioequivalence Criteria, https://doi. org/10.1002/cpt.1270.][Zakharova T.V., Slivkina A.V., Dranitsyna MA The application of the ICA method and window dispersion in the study of bioequivalence pf drugs, XXXV International Seminar on Stability Problems for Stochastic Models, Book of Abstracts, 2018:93-95.][FDA Update: Budeprion XL 300 mg Not Therapeutically Equivalent to Wellbutrin XL 300 mg: https://www.fda.gov/Drugs/DrugSafety/Post marketDrugSafetyInformationforPatientsandProviders/ucm322161.htm.][FDA Approval Package for Bupropion HCl extended-release (XL) 300 mg Tablets https://www.accessdata.fda.gov/drugsatfda_docs/ nda/2006/077415.pdf.]