O Regulamento (UE) N° 536/2014 relativo aos ensaios clínicos de medicamentos para uso humano: oportunidades de inovação e desafios éticos

Autores

DOI:

https://doi.org/10.17566/ciads.v10i3.775

Palavras-chave:

Harmonização, Transparência, Competitividade, Inovação, Ética

Resumo

Objetivo: identificar os principais aspetos inovadores do Regulamento relativo aos ensaios clínicos de medicamentos para uso humano, em termos de oportunidades para a investigação e desenvolvimento e refletir sobre os desafios éticos deste novo quadro legal. Metodologia: estudo documental, descritivo, comparativo, do Regulamento face à Diretiva 2001/20/CE, e leitura de bibliografia publicada no PubMed, usando termos de pesquisa combinados ou simples como clinical, trials, European, Regulation, Directive, opportunities, challenges e innovation. Resultados: os principais aspetos inovadores identificados foram o Portal da União Europeia para submissão do dossiê do ensaio clínico e avaliação conjunta entre os Estados-Membros envolvidos num ensaio clínico; disponibilização pública de informação, resultados dos ensaios e um sumário de resultados para leigos; foram criadas a figura do copromotor, categorias de ensaios em função do risco; estabelecidos novos procedimentos para obtenção de consentimento informado e requisitos para uma maior proteção para os indivíduos mais vulneráveis; e definido o quadro normativo para a realização de ensaios clínicos em situação de emergência. Discussão: estão previstos procedimentos que visam contrariar a perda de competitividade da Europa, promovendo a inovação, alguns dos quais não estão isentos de questionamento ético. Conclusão: a simplificação, harmonização e maior transparência em todo o processo de submissão e condução dos ensaios clínicos tem o potencial de promover a investigação, mas traz alguns aspetos inquietantes em matéria de proteção dos participantes nos ensaios clínicos.

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Biografia do Autor

  • Maria Alexandra Ribeiro, Universidade Nova de Lisboa

    Doutora em Biologia, Fisiologia e Bioquímica, Faculdade de Ciências,  Universidade de Lisboa, Lisboa, Portugal; professora auxiliar convidada, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; presidente, Comissão de Ética para a Investigação Clínica (CEIC), Lisboa, Portugal. https://orcid.org/0000-0003-1947-0523. E-mail: maribeiro@nms.unl.pt

Referências

Parlamento Europeu e Conselho Europeu. Regulamento (UE) No 536/2014 do Parlamento Europeu e do Conselho de 16 de abril de 2014 relativo aos ensaios clínicos de medicamentos para uso humano e que revoga a Diretiva 2001/20/CE. J Of da União Eur. 2014; L 158:1–76.

Parlamento Europeu e Conselho Europeu. Diretiva 2001/20/CE do Parlamento Europeu e do Conselho de 4 de abril de 2001 relativa à aproximação das disposições legislativas, regulamentares e administrativas dos Estados-Membros respeitantes à aplicação de boas práticas clínicas na condução dos ensaios clínicos de medicamentos para uso humano. J Of da União Eur. 2001;121:34–44.

Gluud C, Kubiak C, Whitfield K, Byrne J, Huemer K, Thirstrup S, et al. Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network ( ECRIN ) countries. Trials. 2012;13:27.

Hernandez R, Cooney M, Dualé C, Gálvez M, Gaynor S, Kardos G, et al. Harmonisation of ethics committees’ practice in 10 European countries. J Med Ethics. 2009;35(11):696–700.

European Clinical Research Infrastructures Network - Transnational Working Groups (ECRIN-TWG). Deliverable 5. Meetings on the legislative and regulatory frameworks for clinical research in Europe. 2008.

Hartmann M. Impact assessment of the European Clinical Trials Directive: A longitudinal, prospective, observational study analyzing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries. Trials. 2012;13:53.

Boer AD, Schipper I. New EU regulation on clinical trials: the impact on ethics and safeguards for participants. Indian J Med Ethics. 2013;10(2):106–9

Califf RM. Clinical trials bureaucracy: Unintended consequences of well-intentioned policy. Clin Trials. 2006;3(6):496–502.

Petrini C. Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use: an overview. Ann Ist Super Sanità. 2014;50(4):317–321.

European Clinical Research Infrastructures Network - Transnational Working Groups (ECRIN-TWG). Deliverable 4. Clinical research in Europe: national differences in legislative and regulatory frameworks. 2008.

European Commission. Commission Staff Working Document. Impact assessment report on the revision of the “Clinical Trials Directive” 2001/20/EC accompanying the document Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. 2012.

Liddell K, Chamberlain D, Menon DK, Bion J, Kompanje EJO, Lemaire F, et al. The European Clinical Trials Directive revisited: The VISEAR recommendations. Resuscitation. 2006;69(1):9–14.

Hartmann M, Hartmann-Vareilles F. The Clinical Trials Directive: How Is It Affecting Europe’s Noncommercial Research. PLoS Clin Trials. 2006;1(2):e13.

Kenter MJH, Cohen AF. Re-engineering the European Union Clinical Trials Directive. Lancet. 2012;379:1765–7.

Abou-El-Enein M, Schneider CK. Deciphering the EU clinical trials regulation. 2016;34(3):231–3

Scavone C, Mauro G, Pietropaolo M, Alfano R, Berrino L, Rossi F, et al. The European Clinical Trials Regulation (No 536/2014): changes and challenges. Expert Rev Clin Pharmacol. 2019;12(11):1027–1032.

Gøtzsche PC. Deficiencies in proposed new EU regulation of clinical trials. BMJ. 2013;346(7890):9–12.

Frewer LJ, Coles D, Lans IA van der, Schroeder D, Champion K, Apperley JF. Impact of the European Clinical Trials Directive on prospective academic clinical trials associated with BMT. Bone Marrow Transplant. 2011;46:443–447.

Jeong S, Sohn M, Kim JH, Ko M, Seo HW, Song YK, et al. Current globalization of drug interventional clinical trials: Characteristics and associated factors, 2011-2013. Trials. 2017;18:288.

Walker E, Hankins MC, White SM. The effect of the European Clinical Trials Directive on published drug research in anaesthesia. 2009;64:984–989.

Giannuzzi V, Altavilla A. Clinical Trial Application in Europe: What Will Change with the New Regulation ? Sci Eng Ethics. 2016;22(2):451–66.

Cave E. EU clinical trials regulation 2014: Fetter or facilitator? Med Law Int. 2018;18(2–3):179–194.

Flear ML. The EU Clinical Trials Regulation: Key Priorities, Purposes and Aims and the Implications for Public Health. J Med Ethics. 2016;42(3):192–8.

European Medicines Agency (EMA). Clinical Trials Information System (CTIS) Training - Information update on progress. Vol. 31. 2021.

Barnes A, Patrick S. Lay Summaries of Clinical Study Results: An Overview. Pharmaceut Med. 2019;33(4):261–268.

Djurisic S, Rath A, Gaber S, Garattini S, Bertele V, Ngwabyt SN, et al. Barriers to the conduct of randomised clinical trials within all disease areas. Trials. 2017;18:360.

Toussaint B. EU Clinical Trials Regulation. Lancet. 2013;381(9879):1719–20.

Lemaire F, Matei M, Juvin P. New European Regulation for Clinical Trials of Medicinal Products. Am J Respir Crit Care Med 2015;191(1):16–18.

Madeira C, Santos F, Kubiak C, Demotes J. Transparency and accuracy in funding investigator-initiated clinical trials: a systematic search in clinical trials databases. BMJ Open. 2019;9:e023394.

European Commission. Council conclusions on personalised medicine for patients (2015/C 421/03). Of J Eur Union. 2015. C 421:1-5.

Gefenas E, Cekanauskaite A, Lekstutiene J, Lukaseviciene V. Application challenges of the new EU Clinical Trials Regulation. Eur J Clin Pharmacol. 2017;73(7):795–798.

Kim D, Hasford J. Redundant trials can be prevented if the EU clinical trial regulation is applied duly. BMC Med Ethics. 2020;21:107.

Lukaseviciene V, Hasford J, Lanzerath D, Gefenas E. Implementation of the EU clinical trial regulation transforms the ethics committee systems and endangers ethical standards. J Med Ethics. 2020;1–6.

Shaw D, Townend D. Division and discord in the clinical trials regulation. J Med Ethics. 2016;42(11):729–32.

Heringa J, Dute J. The proposed EU-regulation on clinical trials on medicinal products: An unethical proposal? Eur J Health Law. 2013;20(4):347–62.

Petrini C. What is the role of ethics committees after Regulation (EU) 536/2014? J Med Ethics. 2016;42(3):186–8.

World Medical Association. Declaration of Helsinki, Ethical Principles for Scientific Requirements and Research Protocols. Bull World Health Organ. 2013;79(4):373.

Unesco. Universal Declaration on Bioethics and Human Rights: UNESCO United Nations Educational, Scientific and Cultural Organization Universal Declaration on Bioethics and Human Rights: UNESCO; 2005.

International Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. Geneva. Council for International Organizations of Medical Sciences (CIOMS); 2016.

Council of Europe. Guide for Research Ethics Committee Members. Steering Committee on Bioethics. 2012.

European Commission. Regulation (EU) No 536/2014 Questions & Answers. Draft February 2021. 2021 [citado em 24.fev.2021]. Disponivel em: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/regulation5362014_qa_en.pdf

Dal-Ré R, Carné X. ¿Es tiempo de plantear ensayos clínicos de bajo nivel de intervención sin el consentimiento informado de los participantes? Is it time to discuss on low-intervention clinical trials without participants’ informed consent? Med Clin (Barc). 2018;150(9):345–7.

Westra AE. Ambiguous articles in new EU Regulation may lead to exploitation of vulnerable research subjects. J Med Ethics. 2016;42(3):189–91.

Gamble C, Woolfall K, Williamson P, Appleton R, Young B. New European Union regulation of clinical trials is conflicting on deferred consent in emergency situations. BMJ. 2013;346:f667.

Ostuzzi G, Gastaldon C, Barbui C. Poor implementation of the EU clinical trial regulation is a major threat for pragmatic trials in European countries. Epidemiol Psychiatr Sci. 2020;29(e126):1–3.

Tenti E, Simonetti G, Bochicchio MT, Martinelli G. Main changes in European Clinical Trials Regulation (No 536/2014). Contemp Clin Trials Commun. 2018;11(536):99–101.

Olimid AP, Olmid DA. Ethical review of patient safety and public health in EU clinical trials legislation: impact of COVID-19 pandemic. Rom J Morphol Embryol. 2020;61(1):277-281.

Glasa J, Glasová H. Ensuring an Appropriate Ethics Oversight under the New EU Clinical Trial Regulation: Challenges and Practicalities. Clin Ther. 2017;39(8):e97.

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Publicado

16-09-2021

Edição

Seção

JURISPRUDÊNCIA E LEGISLAÇÃO SANITÁRIA COMENTADAS

Como Citar

1.
O Regulamento (UE) N° 536/2014 relativo aos ensaios clínicos de medicamentos para uso humano: oportunidades de inovação e desafios éticos. Cad. Ibero Am. Direito Sanit. [Internet]. 16º de setembro de 2021 [citado 28º de março de 2024];10(3):211-24. Disponível em: https://www.cadernos.prodisa.fiocruz.br/index.php/cadernos/article/view/775