vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2024-14-5-590-600vedomostiregmed-715Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESОпыт экспертизы клинических исследований биоэквивалентности лекарственных препаратов местного действия, проведенных по процедурам Евразийского экономического союзаExperience in the Examination of Bioequivalence Clinical Trials of Locally Applied and Locally Acting Medicinal Products in Accordance with the Eurasian Economic Union Procedureshttps://orcid.org/0000-0003-1698-2670ИвановаО. Ю.IvanovaO. Yu.

Иванова Ольга Юрьевна.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Olga Yu. Ivanova.

8/2 Petrovsky Blvd, Moscow 127051

ivanovaou@expmed.ruhttps://orcid.org/0009-0004-3985-1985ШиховцоваО. Л.ShikhovtsovaO. L.

Шиховцова Ольга Леонидовна.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Olga L. Shikhovtsova.

8/2 Petrovsky Blvd, Moscow 127051

Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202403112024145590600Copyright © Иванова О.Ю., Шиховцова О.Л., 20242024Иванова О.Ю., Шиховцова О.Л.Ivanova O.Y., Shikhovtsova O.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/715ВВЕДЕНИЕ

ВВЕДЕНИЕ. В процессе экспертизы протоколов клинических исследований лекарственных препаратов местного действия (ЛПМД) выявляются затруднения, возникающие у разработчиков препаратов при выборе дизайна исследований, конечных точек, популяции, групп сравнения и размера выборки. Анализ типичных ошибок в протоколах клинических исследований позволит сократить количество замечаний при экспертизе и ускорит вывод новых препаратов на фармацевтический рынок.

ЦЕЛЬ

ЦЕЛЬ. Проанализировать результаты экспертизы клинических исследований ЛПДМ, проведенных с учетом дополнений к Правилам проведения исследований биоэквивалентности лекарственных препаратов в рамках Евразийского экономического союза (ЕАЭС), оценить основные преимущества введения дополнительных требований и сохраняющиеся трудности в разработке протоколов, представить рекомендации, позволяющие наиболее эффективно применять существующие нормативные правовые требования.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. С момента вступления в силу Приложений № 11, 12 и 13 к Правилам проведения исследований биоэквивалентности лекарственных препаратов в рамках ЕАЭС в августе 2023 г. накоплен достаточный опыт проведения экспертиз протоколов клинических исследований ЛПМД. При анализе протоколов клинических исследований выявлены наиболее часто встречающиеся замечания и предложены рекомендации по их устранению. Отмечено, что затруднения при разработке протоколов исследований ЛПМД чаще всего вызывают выбор и обоснование первичных и вторичных конечных точек, определение популяции исследования, обоснование численности. Показано, что возможная причина данных затруднений, вероятно, связана с отсутствием подробного описания характеристик исследования в нормативных правовых актах ЕАЭС. При этом отмечено, что наименьшее количество трудностей вызывает разработка протоколов исследования кортикостероидных лекарственных препаратов для местного применения, описанная наиболее полно в законодательстве ЕАЭС и научной литературе.

ВЫВОДЫ

ВЫВОДЫ. Проведенный анализ протоколов клинических исследований ЛПМД и соответствующих требований ЕАЭС и международных руководств позволил определить основные проблемы, связанные с выбором первичных и вторичных конечных точек исследования, характеристикой популяции и обоснованием ее численности. Представленные рекомендации помогут заявителям в планировании клинических исследований с целью ускорения вывода лекарственных препаратов на фармацевтический рынок.

INTRODUCTION

INTRODUCTION. The examination of protocols for clinical trials of locally applied and locally acting medicinal products highlights challenges that developers face when selecting the design, endpoints, population, comparison groups, and sample size. An analysis of the most common errors in clinical trial protocols will help minimise the number of comments from protocol reviewers and accelerate the process of bringing novel medicinal products to the pharmaceutical market.

AIM

AIM. This study aimed to analyse the results of evaluating clinical trials of locally applied and locally acting medicinal products conducted with due consideration of the recent additions to the Rules for Conducting Bioequivalence Studies of Medicinal Products within the Eurasian Economic Union (EAEU); assess the main advantages of the added requirements and the challenges remaining in protocol development; and make recommendations for the most effective application of existing laws and regulations.

DISCUSSION

DISCUSSION. The Rules for Conducting Bioequivalence Studies of Medicinal Products within the EAEU were supplemented with Appendices 11, 12, and 13 in August 2023. Since then, protocol reviewers have accumulated sufficient experience in the examination of clinical trial protocols for locally applied and locally acting medicinal products. This article presents the most frequent comments made during the examination of clinical trial protocols and provides recommendations for corrective actions. The most challenging aspects of drafting a protocol for a clinical trial of a locally applied and locally acting medicinal product include the selection and justification of primary/secondary endpoints and the calculation and justification of the population size. The difficulty is probably due to the lack of a detailed description of study characteristics in EAEU laws and regulations. Locally applied and locally acting corticosteroids are the least challenging medicinal products in terms of protocol drafting because EAEU legislation and scientific publications provide the most detailed guidance for them.

CONCLUSIONS

CONCLUSIONS. The analysis of protocols for clinical trials of locally applied and locally acting medicinal products, relevant EAEU requirements, and applicable international guidelines identified several major challenges, including the selection of primary/secondary endpoints, the characterisation of the trial population, and the justification of the sample size. The recommendations presented in this article will help applicants in planning clinical trials aimed at accelerating the launch of medicinal products into the pharmaceutical market.

клинические исследованияпротокол клинического исследованияисследования биоэквивалентностиэкспертиза клинических исследованийлекарственные препараты местного действиякремымазигеликортикостероидыclinical trialsclinical trial protocolbioequivalence studiesclinical research evaluationlocally applied and locally acting medicinal productscreamsointmentsgelscorticosteroidsРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00026-24-01 на проведение прикладных научных исследований (номер государственного учета НИР 124022300127-0).This study was conducted by the Scientific Centre for Expert Evaluation of Medicinal Products as part of the applied research funded under State Assignment No. 056-00026-24-01 (R&D Registry No. 124022300127-0).ReferencesНиязов РР, Рождественский ДА, Васильев АН, Гавришина ЕВ, Драницына МА, Куличев ДА. Регуляторные аспекты регистрации воспроизведенных и гибридных лекарственных препаратов в Евразийском экономическом союзе. 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The authors declare that there are no conflicts of interest present.