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’)10.30895/1991-2919-2021-11-2-94-103vedomostiregmed-340Research ArticleОБЗОРЫREVIEWSРекомендации по программе клинических исследований лекарственных препаратов для профилактики и лечения сахарного диабетаRecommendations on the Clinical Trial Programme for Diabetes Medicineshttps://orcid.org/0000-0003-0934-5067ПроскуринаИ. А.ProskurinaI. A.

Проскурина Ирина Анатольевна, кандидат медицинских наук

Петровский бульвар, д. 8, стр. 2, Москва, 127051

Irina A. Proskurina, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

Proskurina@expmed.ruhttps://orcid.org/0000-0002-7400-8289ПетраневаЕ. В.PetranevaE. A.

Петранева Елена Вилорьевна, кандидат медицинских наук

Петровский бульвар, д. 8, стр. 2, Москва, 127051

Elena V. Petraneva, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

petranevaev@expmed.ruhttps://orcid.org/0000-0001-8583-2372ГорячевД. В.GoryachevD. V.

Горячев Дмитрий Владимирович, доктор медицинских наук

Петровский бульвар, д. 8, стр. 2, Москва, 127051

Dmitry V. Goryachev, Dr. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

Gorachev@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation20212203202111294103Copyright © Проскурина И.А., Петранева Е.В., Горячев Д.В., 20212021Проскурина И.А., Петранева Е.В., Горячев Д.В.Proskurina I.A., Petraneva E.A., Goryachev D.V.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/340

Сахарный диабет представляет собой значимую проблему общественного здравоохранения, является одним из основных хронических неинфекционных заболеваний. Длительность лечения, поэтапность и необходимость индивидуального подхода при проведении терапии сахарного диабета ставят серьезные задачи перед разработчиками новых препаратов. На территории Европейского союза с 2005 г. действует централизованная процедура регистрации новых гипогликемических препаратов, что обеспечивает единство подходов к оценке их эффективности и безопасности. Цель работы – анализ актуальных требований к планированию клинических исследований гипогликемических препаратов, содержащих новые действующие вещества (исключая препараты инсулина). Рекомендации Консенсуса Европейской ассоциации по изучению сахарного диабета (EASD) и Американской диабетической ассоциации (ADA) по диагностике и лечению сахарного диабета 2 типа 2019 г. предлагают пошаговый подход к интенсификации терапии для достижения гликемической цели, который учитывает наличие у пациента сердечно-сосудистых и других заболеваний, функциональных особенностей организма. На основании проведенного анализа документов EASD/ADA и научной литературы предложены рекомендации по основным принципам планирования и проведения клинических исследований на завершающих этапах разработки гипогликемических лекарственных препаратов. Описаны новые подходы к проведению клинических исследований, позволяющие наиболее достоверно оценить эффективность терапии. Стратегия оценки терапевтического эффекта препарата должна быть тщательно спланирована, обоснована, отражена в переменных интереса, дизайне клинического исследования и статистическом анализе его результатов. Основным критерием эффективности в подтверждающих клинических исследованиях гипогликемических лекарственных препаратов должна быть демонстрация преимуществ в отношении улучшения контроля гликемии. В качестве вторичной конечной точки может рассматриваться влияние препарата на массу тела. Обязательным требованием является подтверждение сердечно-сосудистой безопасности препарата и возможные дополнительные преимущества в отношении уменьшения риска развития сердечно-сосудистых заболеваний. В протоколе клинического исследования требуется представить определение интеркуррентных событий и гипогликемии. Всестороннее изучение безопасности нового гипогликемического препарата должно включать выявление предполагаемых или известных эффектов соответствующего класса лекарственных препаратов. Представленные рекомендации могут использоваться разработчиками лекарственных препаратов, а также экспертами, осуществляющими оценку программы клинической разработки гипогликемических препаратов и экспертизу с целью регистрации. 

Diabetes is a serious public health problem and one of the major chronic noncommunicable diseases. A lengthy stepwise treatment, and the need for an individualised approach to antidiabetic therapy, pose serious challenges for medicine developers. For all new hypoglycaemic medicines, there has been a centralised authorisation procedure in the European Union (EU) since 2005, which ensures a unified approach to efficacy and safety assessment. The aim of the study was to analyse current requirements for planning clinical trials of hypoglycaemic medicines containing new active substances (except for insulin products). The recommendations for diagnosis and treatment of type 2 diabetes, prepared by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) in 2019, suggest a step-by-step approach to intensification of treatment to maintain glycaemic targets, which takes account of concomitant cardiovascular or other diseases, and clinical characteristics of patients. The analysis of EASD/ADA documents and scientific literature helped to develop recommendations on the basic principles of planning and conducting clinical trials at the final stages of hypoglycaemic medicine development. The paper describes new approaches to clinical trials, which allow for a more reliable assessment of the treatment effectiveness. The strategy for the assessment of therapeutic effect should be carefully planned, justified, and reflected in variables of interest, clinical trial design, and statistical analysis of the trial results. The main efficacy criterion in confirmatory clinical trials of hypoglycaemic medicines should be the demonstration of benefits in improving glycaemic control. The medicine’s effect on the body weight may be considered as a secondary endpoint. An essential requirement is confirmation of the medicines’ cardiovascular safety, while potential additional benefits are reduction or prevention of risks of cardiovascular disease development. The clinical trial protocol should provide definitions for intercurrent events and hypoglycaemia. A comprehensive safety study of a new hypoglycaemic medicine should involve identification of anticipated or known side effects characteristic of a particular pharmacological class. The provided recommendations may be helpful for medicine developers, and for experts who perform assessment of clinical trial programmes and regulatory submissions for hypoglycaemic medicines.           

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The authors declare that there are no conflicts of interest present.