Наблюдательные исследования как инструмент внедрения в клиническую практику инновационных подходов в онкологии

Хатьков И.Е., Андреяшкина И.И., Аничкина К.А., Пастернак А.В., Прокофьева Е.С., Зайцев Р.Д., Троценко И.Д. Наблюдательные исследования как инструмент внедрения в клиническую практику инновационных подходов в онкологии. Consilium Medicum. 2023;25(6):388–394. DOI: 10.26442/20751753.2023.6.202351

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

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Khatkov IE, Andreyashkina II, Anichkina KA, Pasternak AV, Prokofieva ES, Zaitsev RD, Trotsenko ID. Observational studies as a tool for introducing innovative oncology approaches into clinical practice: A review. Consilium Medicum. 2023;25(6):388–394. DOI: 10.26442/20751753.2023.6.202351

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Аннотация

Рандомизированные клинические исследования (РКИ) сегодня остаются «золотым стандартом» доказательной медицины. С другой стороны, не менее очевидно, что реальная практика предъявляет много новых и важных вопросов, на которые в рамках РКИ ответить сложно: насколько портрет реального пациента соответствует критериям включения в исследование; каковы эффективность и безопасность препарата у коморбидных и пожилых пациентов; как отклонения от режима приема влияют на безопасность и др. Внедрение инновационных подходов в онкологии происходит несоизмеримо более быстрыми темпами по сравнению с другими дисциплинами. Именно поэтому здесь важен взвешенный анализ эффектов инноваций в реальной практике. Регуляторные органы, понимая это, демонстрируют готовность рассматривать и активно поддерживать исследования реальной клинической практики (real-world evidence, real world data) в рамках заявок на регистрацию препаратов, что является мощным стимулом к развитию данного направления. Целью статьи является анализ регуляторных подходов США и Европы к исследованиям реальной клинической практики при рассмотрении регистрационных заявок лекарственных препаратов, а также обсуждение опыта организации наблюдательного исследования эффективности отдельных лекарственных препаратов для лечения онкологических заболеваний в Москве как уникального для России примера взаимодействия регуляторных органов и экспертного сообщества онкологов.

Ключевые слова: real-world evidence, real world data, клинические исследования, наблюдательное исследование, реальная клиническая практика, московское онкологическое общество

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Randomized clinical trials (RCTs) are the “gold standard” of evidence-based medicine. However, it is no less evident that real practice presents many new and important questions that are difficult to answer in the RCT. To what extent does the real patient meet the criteria for inclusion in the study? What are the efficacy and safety of the drug in comorbid and elderly patients? How deviations from the treatment regimen affect safety, etc. The introduction of innovative oncology approaches is disproportionately faster than in other fields. That is why a balanced analysis of the effects of innovation in real-world practice is relevant. Regulatory authorities are aware of this and demonstrate a willingness to consider and actively support real-world evidence research as part of drug applications, which is a powerful incentive for developing this area. The purpose of the article is to analyze the regulatory approaches in the United States and Europe to real-world studies when considering drug applications and to discuss the experience of organizing an observational study of the effectiveness of individual drugs for the treatment of oncological diseases in Moscow as a unique example of interaction between regulatory authorities and the expert community of oncologists.

Keywords: real-world evidence, real world data, clinical studies, observational study, real clinical practice, Moscow Cancer Society

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1. Subbiah V. The next generation of evidence-based medicine. Nat Med. 2023;29:49-58.
2. Dickson D, Johnson J, Bergan R, et al. The master observational trial: a new class of master protocol to advance precision medicine. Cell. 2020;180:9-14.
3. Park JJH, Siden E, Zoratti MJ, et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20:572.
4. Allen A, Siefkas A, Pellegrini E, et al. A Digital Twins Machine Learning Model for Forecasting Disease Progression in Stroke Patients. Appl Sci. 2021;11:5576.
5. Walsh JR, Smith AM, Pouliot V, et al. Generating Digital Twins with Multiple Sclerosis Using Probabilistic Neural Networks. for the Multiple Sclerosis Outcome Assessments Consortium. bioRxiv. 2020.
6. Concato J, Corrigan-Curay J. Real-world evidence – where are we now? N Engl J Med. 2022;386:1680-2.
7. Sherman RE, Davies KM, Robb MA, et al. Accelerating development of scientific evidence for medical products within the existing US regulatory framework. Nat Rev Drug Discov. 2017;16:297-8.
8. Постановление Правительства России от 02.05.2012 №413. Режим доступа http://government.ru/docs/all/82122. Ссылка активна на 12.03.2023
9. Routledge P. 150 years of pharmacovigilance. Lancet. 1998;351:1200-1.
10. Commission on Anaesthetics. Lancet. 1893:629-38.
11. Available at: https://www.who.int/teams/regulation-prequalification/regulation-and-safety/pharmacovigilance/networ... Accessed: 10.05.2023
12. Dang A. Real-World Evidence: A Primer. Pharmaceutical Medicine. 2023;37:25-36.
13. Hemkens LG, Contopoulos-Ioannidis DG, Ioannidis JPA. Routinely collected data and comparative effectiveness evidence: promises and limitations. Can Med Assoc J. 2016;188:E158-64.
14. Administration Food and Drug Evaluating Inclusion and Exclusion Criteria in Clinical Trials; Workshop Report. 2018. Docket number: FDA-2018-N-0129.
15. Van Spall HG, Toren A, Kiss A, Fowler R. Eligibility Criteria of Randomized Controlled Trials Published in High-Impact General Medical Journals. JAMA. 2007;11(297):1233-40.
16. Inclusion Across the Lifespan, Marie Bernard, National Institute on Aging, National Institute of Health. Available at: https://healthpolicy.duke.edu/events/evaluating-inclusion-and-exclusion-criteria-clinical-trials. Accessed: 16.04.2018.
17. Review of Eligibility Criteria From a Sample of Approved Drugs and Biologics, Kaveeta Vasisht, Food and Drug Administration. Available at: https://healthpolicy.duke.edu/events/evaluating-inclusion-and-exclusion-criteria-clinical-trials. Accessed: 16.04.2018.
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19. Cochrane AL. Effectiveness and efficiency: random reflection on health services. Public Health. 1973;4(87):149.
20. Haynes B. Can it work? Does it work? Is it worth it? The testing of healthcare interventions is evolving. BMJ. 1999;7211(319):652-3.
21. High Level Pharmaceutical Forum 2005–2008. Final Conclusions and Recommendations of the Pharmaceutical Forum. Available at: http://www.bgpharma.bg/bulletin/read/edition/8/file/final_conclusions_en.pdf. Accessed: 11.07.2023.
22. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-90.
23. Marrero JA, Kudo M, Venook AP, et al. Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: the GIDEON study. J Hepatol. 2016;65:1140-7.
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29. Feinberg BA, Gajra A, Zettler ME, et al. Use of Real-World Evidence to Support FDA Approval of Oncology Drugs. Value Health. 2020;23(10):1358-65.
30. Purpura CA, Garry EM, Honig N, et al. The Role of Real- World Evidence in FDA- Approved New Drug and Biologics License Applications. Clin Pharmacol Ther. 2022;1(111):135-44.
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Авторы

И.Е. Хатьков¹, И.И. Андреяшкина¹, К.А. Аничкина¹, А.В. Пастернак¹, Е.С. Прокофьева², Р.Д. Зайцев², И.Д. Троценко*³

¹ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия;
²АНО «Московский центр инновационных технологий в здравоохранении», Москва, Россия;
³ФГАОУ ВО «Российский университет дружбы народов», Москва, Россия
*ivan.trotsenko@mosoncolog.ru

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Igor E. Khatkov¹, Irina I. Andreyashkina¹, Kristina A. Anichkina¹, Alina V. Pasternak¹, Elizaveta S. Prokofieva², Roman D. Zaitsev², Ivan D. Trotsenko*³

¹Loginov Moscow Clinical Scientific Center, Moscow, Russia;
²Moscow Center for Innovative Technologies in Healthcare, Moscow, Russia;
³People’s Friendship University of Russia (RUDN University), Moscow, Russia
*ivan.trotsenko@mosoncolog.ru

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