Abstract
Experimentation is essential in scientific research for the advancement of knowledge. The objective of experimentation is in itself good, insofar as it aims at improving the conditions of human’s health and wellbeing, but it should be adequately justified in relation to the protection of the interests and fundamental rights of the subject being experimented on. The chapter analysis the main ethical requirements of experimentation on human beings in general, focusing on particularly vulnerable categories (minors, women, people in developing Countries). A special focus is dedicated to innovative treatments, early access, unexperimented or not yet experimented drugs and the so called ‘compassionate use’.
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Notes
- 1.
Starting from the Nuremberg Code (1947), through the Declaration of Helsinki (1964 and successive revisions) and the drawing up of the guidelines for clinical practice (Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects, adopted in 1993 with successive revisions; Good Clinical Practice approved by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use in 2002), up to the documents of international and community importance, with different levels of bindingness. In particular the following deserve mention: UNESCO (2005); Council of Europe (1997, 2004); Regulation of the European Union No. 536/2014 of 16 April 2014 on clinical trials of drugs for human use, which repeals directive 2001/20/EC. In this context see also: European Medicines Agency (EMA) (2016); World Health Organization (WHO) (2002, 2011).
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See documents on the topics on an European level: European Medicines Agency (EMA) (2008, 2012); European Commission (2013); European Commission ad hoc group (2008). The main Opinions on the topics in Europe: Nuffield Council on Bioethics (2015); U.K. Medical Research Council (2004); Italian Committee for Bioethics (2012); Working Party of Research Ethics Committees in Germany (2010). On an international level: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2000); International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2016). In USA: American Academy of Paediatrics – Committee on Bioethics (2016); U.S. National Academy of Sciences (Committee on Clinical Research Involving Children) (2004); U.S. National Academy of Sciences (Committee on Paediatric Studies-Institute of Medicine) (2012); U.S. National Institutes of Health (2016); U.S. Presidential Commission for the Study of Bioethical Issues (2013).
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Wendler (2006), pp. 229–234.
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Miller and Nelson (2006), pp. S25–S30.
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The regulation on international level: UN Convention of the Rights of the Child, 1989; Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine, 1997; Additional Protocol to the Convention on Human Rights and Biomedicine concerning Biomedical Research, 2005. Regulation on European level: Charter of Fundamental Rights of European Union, 2000 (2000/C 364/01); Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data; Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use; Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 (Text with EEA relevance); Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (Text with EEA relevance); Regulation (EU) 679/2016 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation); European Parliament Resolution of 15 December 2016 on the regulation on paediatric medicines (2016/2902(RSP)).
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While in 1977 the Food and Drug Administration (FDA) in its General Considerations for the Clinical Evaluation of Drugs and in 1982 the World Health Organisation in its Proposed International Guidelines recommended the exclusion of women from experimentations, it is in 1988 that the FDA in its Guideline for the Format and Content of the Clinical and Statistical Sections of New Drug Application recommends the analysis of data differentiated according to sex in clinical trials. In 1993 once again the Food and Drug Administration issues the Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs, expressing the hope for the inclusion of women in the experimentation protocols so as to guarantee an equal representation. Along the same line are the International Ethical Guidelines for Biomedical Research Involving Human Subjects (1993, revised in 2002), which recommend researchers, sponsors and ethics committees to not exclude women of child bearing age from experimentation, not considering the potential of pregnancy a sufficient reason to limit their participation and recognising women the capacity to take a “rational decision” in taking part in research.
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Franconi et al. (2007), pp. 81–97.
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On the topics see the Opinion of the National Ethics Council in Europe: Austrian Bioethics Commission at the Federal Chancellery (2009); Belgian Advisory Committee on Bioethics (2004, 2015); European Medicines Agency (EMA) (2005, 2005); Italian National Bioethics Committee (2008). In USA: Columbia University Institutional Review Board (2012); John Hopkins University Center for Communication Programs (2003); The American College of Obstetricians and Gynecologists (2015); The Society for Women’s Health Research – United States Food and Drugs Administration Office of Women’s Health (2011); U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Office of Research on Women’s Health (2011); U.S. Government Accountability Office (1992); U.S. Government Accountability Office (2001); U.S. Food and Drug Administration (1993); U.S. National Institute of Health (2001). In other countries and on international level: Health Canada (2013); International Conference on Harmonisation (ICH) (2004); World Health Organization (WHO) (1995, 1998, 2010).
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CIOMS 2016, Commentary on Guideline 19.
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On the topics see: French National Consultative Ethics Committee for Health and Life Sciences (2003); Italian Committee for Bioethics (2011, 2017); European Group on Ethics in Science and New Technologies (EGE) (2003); Nuffield Council on Bioethics (2005); U.S. Food and Drug Administration (2013, 2016); U.S. National Bioethics Advisory Commission (2001); U.S. National Institute of Health (2001); Marshall (2007); Neves (2009).
- 15.
In the context of international guidelines the ethical criteria of experimentation with particular reference to developing Countries have been elaborated in International Ethical Guidelines for Biomedical Research Involving Human Subjects 2002, which updated the 1993 guidelines of the Council for International Organizations of Medical Sciences in collaboration with the World Health Organization; Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, in its most recently developed form by the World Medical Association (adopted in 1964, revised in 1975, 1983, 1989, 1996, 2000 and 2008), Working Party for the Elaboration of Guides for Research Ethics Committee Members (CDBI, 2010, Rev. 1. 2).
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See art. 37 of the Declaration of Helsinki (updated in October 2013) that provides for the possibility of “unproven interventions in clinical practice”. It allows the use, under the responsibility of the doctor and with the consent of the patient or his legal representative, of “an unproven intervention”, when there are no proven treatments or other known interventions have proved ineffective, and after seeking expert opinion on the subject. The doctor must be convinced that this drug could “constitute a hope to save the life, restore the physical integrity or alleviate the suffering of the patient”. The article adds that “this intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information should be recorded and made publicly available when appropriate”. In one of the many drafts of the Universal Declaration on Bioethics and Human Rights of UNESCO, art. 16 of Scientific and Rational Method, after pointing out that every decision and practice should be based on the best scientific information available, stressed that (v) “be considered individually, allowing for the possibility of exceptions to general rules and practices”. The article was then removed from the final version, but it is the sign of a debate within the international community itself.
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‘Expanded access’ refers to treatment offered to patients in the absence of other effective treatment, emergency for individual and public health. Nevertheless, the spread of contagion cannot be sufficient to allow compassionate treatment only in these circumstances and thus result as being an advantage for these patients. If one considers the point of view of the person affected by a rare disease, with high mortality but not contagious, the lack of danger of its spread would paradoxically deprive these patients of an opportunity that others instead have in trying a treatment.
- 19.
The expression “compassionate use” can be traced in art. 83 of EC Regulation no. 726/2004, that authorizes individual states to derogate from the Community rules for the marketing of drugs in the event that a group of patients with a chronic, seriously debilitating or life-threatening illness, cannot be treated satisfactorily with an authorized medicinal product. EC Regulation no. 726/2004 was amended by Regulation no. 1394/2007. The latter introduces for the first time the definition of “advanced therapies”, including not only gene therapy and somatic cell therapy, as well as tissue engineered products. The main innovations introduced by the Regulation include: the establishment of an expert committee (Committee for Advanced Therapies), within the European Medicines Agency (EMA); the adoption of new requirements for quality, safety and traceability of the donation, procurement and control; the adoption of new regulatory procedures for classification and certification; support for small and medium businesses with incentives to promote entrepreneurship. In addition, Regulation stipulates that each Member State should standardize the production and use of advanced therapies for individual patients, treated in national public facilities, and therefore not aimed at placing on the market and commercialization.
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Palazzani, L. (2019). Scientific Research and Experimenting on Human Beings. In: Innovation in Scientific Research and Emerging Technologies. Springer, Cham. https://doi.org/10.1007/978-3-030-16733-2_1
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