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’)10.30895/1991-2919-2020-10-2-111-120vedomostiregmed-293Research ArticleОБЗОРЫREVIEWSСовременные подходы к планированию и проведению клинических исследований лекарственных препаратов для лечения болезни КронаCurrent Approaches to Planning and Conducting Clinical Trials of Medicinal Products for the Treatment of Crohn's Diseasehttps://orcid.org/0000-0002-8930-4689БогдановА. Н.BogdanovА. N.

Богданов  Александр Николаевич - доктор медицинских наук.

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

Aleksandr N. Bogdanov - Dr. Sci. (Med.).

8/2 Petrovsky Blvd, Moscow 127051

bogdanov@expmed.ruhttps://orcid.org/0000-0001-6433-9781ГорбуноваЕ. В.GorbunovaE. V.

Горбунова Екатерина Владимировна

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

Ekaterina V. Gorbunova

8/2 Petrovsky Blvd, Moscow 127051

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

Горячев Дмитрий Владимирович - доктор медицинских наук.

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

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

8/2 Petrovsky Blvd, Moscow 127051

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

Петранева Елена Вилорьевна - кандидит медицинских наук.

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

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

8/2 Petrovsky Blvd, Moscow 127051

petranevaev@expmed.ruФедеральное государственное бюджетное учреждение Научный центр экспертизы средств медицинского применения Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202020062020102111120Copyright © Богданов А.Н., Горбунова Е.В., Горячев Д.В., Петранева Е.В., 20202020Богданов А.Н., Горбунова Е.В., Горячев Д.В., Петранева Е.В.Bogdanov А.N., Gorbunova E.V., Goryachev D.V., Petraneva E.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/293

Развитие знаний о заболевании, появление биологических препаратов, предназначенных для патогенетического лечения болезни Крона, послужили основанием для разработки объективных методов оценки активности патологического процесса, что, в свою очередь, повлияло на изменение научных подходов к планированию клинических исследований в этой области. На сегодняшний день обновлены многие международные рекомендации, относящиеся к планированию, проведению и анализу результатов клинических исследований, накоплен значительный опыт клинических исследований лекарственных препаратов, предназначенных для лечения болезни Крона. Это диктует необходимость пересмотра методологического подхода к планированию программы клинических исследований. Цель работы — разработка требований к планированию и экспертной оценке клинических исследований, проводимых с целью регистрации лекарственных препаратов для лечения болезни Крона. В работе проведен анализ нормативных документов и рекомендаций, данных научной литературы по лечению болезни Крона и описана методология планирования клинических исследований. Описана эволюция подходов к планированию клинических исследований с момента появления биологических лекарственных препаратов. Обоснована необходимость единства концепции клинического исследования, включающей цели, оцениваемый терапевтический эффект, дизайн и выбор метода статистического анализа. Представлено научное обоснование необходимости применения комбинированной первичной конечной точки, включающей эндоскопическую ремиссию и результаты лечения, оцениваемые самим пациентом. Приведены критерии включения пациентов в клинические исследования лекарственных препаратов по показаниям «достижение и/или поддержание ремиссии заболевания». Рассмотрены основные интеркуррентные события, их влияние на терапевтический эффект, предложены подходы к планированию конечных точек, включающие оценку интеркуррентных событий. В работе подчеркивается необходимость соответствия принципов планирования и проведения клинических исследований III фазы научно обоснованным стратегиям снижения риска некорректной оценки эффективности и безопасности новых лекарственных препаратов для лечения болезни Крона и соответствия полученных результатов требованиям регуляторных органов на этапе регистрации препарата.

Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field. To date, many international recommendations related to planning, conduct of clinical trials, and analysis of their results, have been updated. Considerable experience has been gained with clinical trials of medicines intended for the treatment of Crohn’s disease. Therefore, the methodological approach to the planning of pivotal clinical studies needs to be reviewed. The aim of the study was to develop requirements for planning and expert evaluation of clinical trials conducted with the aim of obtaining marketing authorisation for medicinal products for the treatment of Crohn’s disease. The paper analyses regulations, recommendations, and scientific literature on the treatment of Crohn’s disease and describes the methodology for planning clinical trials. It describes the evolution of approaches to clinical research planning since biological medicines appeared. The authors substantiate the need for an integrated concept of clinical research, which covers goals, estimated therapeutic effect, design, and choice of the statistical analysis method. They also provide scientific arguments in favour of a combined primary endpoint including endoscopic remission and the assessment of treatment results by the patient. The paper lists patient eligibility criteria in terms of “inducing and/or maintaining remission of the disease”. The authors analyse the main intercurrent events, their influence on the therapeutic effect, and propose approaches to the planning of endpoints, including assessment of intercurrent events. The paper highlights the fact that the principles of planning and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation.

клиническое исследованиерегистрацияболезнь Кронадизайн клинических исследованийконечные точкипопуляцияремиссияинтеркуррентные событияclinical studymarketing authorisationCrohn’s diseaseclinical trial designendpointspopulationremissionintercurrent eventsРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00003-20-00 на проведение прикладных научных исследований (номер государственного учета НИР AAAA-A18-118021590049-0).The study reported in this publication was carried out as part of a publicly funded research project No. 056-00003-20-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. AAAA-A18-118021590049-0)ReferencesМаев ИВ, Андреев ДН. Новые подходы к диагностике и лечению болезни Крона. Терапевтический архив. 2014;86(8):4—12.Maev IV, Andreev DN. New approaches to the diagnosis and treatment of Crohn's disease. 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The authors declare that there are no conflicts of interest present.