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The Principle of the Primacy of the Human Subject and Minimal Risk in Non-Beneficial Paediatric Research

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Abstract

Non-beneficial paediatric research is vital to improving paediatric healthcare. Nevertheless, it is also ethically controversial. By definition, subjects of such studies are unable to give consent and they are exposed to risks only for the benefit of others, without obtaining any clinical benefits which could compensate those risks. This raises ethical concern that children participating in non-beneficial research are treated instrumentally; that they are reduced to mere instruments for the benefit of science and society. But this would make the research incompatible with the widely endorsed principle of the primacy of the human subject (henceforth PP), which stipulates that the interests of the participating individual should prevail over the interests of science and society. This paper deals with this conflict. It analyses solutions to this problem developed in the literature, and shows that they are unsuccessful. Finally, it offers a new idea of how to reconcile the conduct of non-beneficial paediatric research with the PP. The paper argues for a new formula of the PP, and shows that it implies a specific non-comparative definition of the minimal risk threshold.

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Notes

  1. I omit here the insightful question of whether developing dispositions for helping others or being altruistic towards others constitutes a developmental benefit for the child herself at all or whether it is instead a benefit for a society (Wendler 2010).

  2. Feinberg describes these interests in the following way: “In this category are the interests in the continuance for a foreseeable interval of one’s life, and the interests in one’s own physical health and vigor, the integrity and normal functioning of one’s body, the absence of absorbing pain and suffering or grotesque disfigurement, minimal intellectual acuity, emotional stability, the absence of groundless anxieties and resentments, the capacity to engage normally in social intercourse and to enjoy and maintain friendships, at least minimal income and financial security, a tolerable social and physical environment, and a certain amount of freedom from interference and coercion ... they are the very most important interests a person has, and cry out for protection, for without their fulfillment, a person is lost. But in another way, they are relatively trivial goods, necessary but grossly insufficient for a good life” (1984, 37).

References

  • Ackerman, T.F. 1979. Fooling ourselves with child autonomy and assent in nontherapeutic clinical research. Clinical Research 27(5): 345–348.

  • Ackerman, T.F. 1980. Moral duties of parents and nontherapeutic clinical research procedures involving children. Bioethics Quarterly 2(2): 94–111.

  • Andorno, R. 2009. Human dignity and human rights as a common ground for a global bioethics. Journal of Medicine and Philosophy 34(3): 223–240.

  • ––––– 2013. The dual role of human dignity in bioethics. Medicine, Health Care and Philosophy 16(4): 967–973.

  • Bartholome, W.G. 1976. Parents, children, and the moral benefits of research. The Hastings Center Report 6(6): 44–45.

  • Bartholome, W.G. 1977. The ethics of non-therapeutic clinical research on children. In The research involving children: Appendix to Report and Recommendations. 3.1-3.22. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Washington D.C.

  • Binik, A. 2014. On the minimal risk threshold in research with children. The American Journal of Bioethics 14(9): 3–12.

  • ––––– 2017. A defense of the-risks-of-daily-life. Kennedy Institute of Ethics Journal 27(3): 413.

  • ––––– 2018. Does benefit justify research with children? Bioethics 32(1): 27–35.

  • Binik, A., and C. Weijer. 2014. Why the debate over minimal risk needs to be reconsidered. Journal of Medicine and Philosophy 39(4): 387–405.

  • Broström, L., and M. Johansson. 2014. Involving children in non-therapeutic research: On the development argument. Medicine, Health Care and Philosophy 17(1): 53–60.

  • Council for International Organizations of Medical Sciences (CIOMS) 2016. International ethical guidelines for health-related research involving humans. Geneva. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf. .

  • Council of Europe. 1997a. Convention for the protection of human rights and dignity of the human beings with regard to the application on biology and medicine. Convention on human rights and biomedicine. CETS 164. Oviedo, Spain. https://rm.coe.int/168007cf98. Accessed December 18, 2020.

  • ––––– 1997b. Explanatory report to the Convention for the protection of human rights and dignity of the human beings with regard to the application on biology and medicine. Convention on human rights and biomedicine. https://rm.coe.int/16800ccde5. Accessed December 18, 2020.

  • ––––– 2005a. Additional Protocol to the Convention on human rights and biomedicine concerning biomedical research. CETS 195. Strasbourg, France. https://rm.coe.int/168008371a. Accessed December 18, 2020.

  • ––––– 2005b Explanatory report to Additional Protocol to the Convention on human rights and biomedicine concerning biomedical research. Strasbourg, France. https://rm.coe.int/16800d3810. Accessed December 18, 2020.

  • DeGrazia, D., M. Groman, and L. M. Lee. 2017. Defining the boundaries of a right to adequate protection: A new lens on pediatric research ethics. Journal of Medicine and Philosophy 42(2): 132–153.

  • Diekema, D.S. 2011. Revisiting the best interest standard: Uses and misuses. The Journal of Clinical Ethics 22(2): 128–133

  • Elliston, S. 2007. The best interests of the child in healthcare. Routledge.

  • Emanuel, E.J., D. Wendler, and C. Grady. 2000. What makes clinical research ethical?. JAMA 283(20): 2701–2711.

  • Emanuel, E.J. 2013. Reconsidering the Declaration of Helsinki. The Lancet 381(9877): 1532–1533.

  • European Union. 2001. 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. OJ L 121, 1.5.2001, p. 34–44 with further amendments.https://eur-lex.europa.eu/eli/dir/2001/20/2009-08-07. Accessed December 18, 2020.

  • ––––– 2008. Ethical considerations for clinical trials on medicinal products conducted with the paediatric population. Recommendations of the ad hoc group for the development of implementing guidelines for Directive 2001/20/EC relating to good clinical practice in the conduct of clinical trials on medicinal products for human use. https://ec.europa.eu/health//sites/health/files/files/eudralex/vol-10/ethical_considerations_en.pdf. Accessed December 18, 2020.

  • ––––– 2014. Regulations (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. OJ L 158, 27.5.2014, p. 1–76.https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32014R0536. Accessed December 18, 2020.

  • ––––– 2017. Ethical considerations for clinical trials on medicinal products conducted with minors Recommendations of the expert group on clinical trials for the implementation of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use. https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-10/2017_09_18_ethical_consid_ct_with_minors.pdf. Accessed July 18, 2021.

  • Feinberg J. 1984. The moral limits of the criminal law. Vol. I: Harm to others. New York/Oxford: Oxford University Press 1984.

  • Fisher, C.B., S.Z. Kornetsky, and E.D. Prentice. 2007. Determining risk in pediatric research with no prospect of direct benefit: Time for a national consensus on the interpretation of federal regulations. The American Journal of Bioethics 7(3): 510.

  • FitzPatrick, W. 2021. Morality and evolutionary biology. The Stanford encyclopedia of philosophy (Spring 2021 Edition), ed. E. N. Zalta. https://plato.stanford.edu/archives/spr2021/entries/morality-biology. Accessed January 12, 2021.

  • Fletcher, G. 2016a. The philosophy of well-being: An introduction. London: Routledge.

  • Fletcher, G. (ed). 2016b. The Routledge handbook of the philosophy of well-being. London: Routledge.

  • Freedman, B., A. Fuks, and C. Weijer. 1993. In loco parentis: Minimal risk as an ethical threshold for research upon children. Hastings Center Report 23(2): 13–19.

  • Gaylin, W. 1982.The competence of children: No longer all or none. The Hastings Centre Report 12(2): 33–38.

  • Helgesson, G., and S. Eriksson. 2008. Against the principle that the individual shall have priority over science. Journal of Medical Ethics 34(1): 54–56.

  • Helgesson, G.. 2011. The moral primacy of the human being: A reply to Parker. Journal of Medical Ethics 37(1): 56–57.

  • Human, D. and S.S. Fluss. 2001. The World Medical Association’s Declaration of Helsinki: Historical and contemporary perspectives. Geneva: World Medical Association.

  • International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2016. ICH Harmonised Guideline Integrated Addendum To ICH E6(R1): Guideline For Good Clinical Practice E6(R2). https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf. Accessed December 18, 2020.

  • Kopelman, L.M. 1997a. Children and bioethics: Uses and abuses of the best-interests standard. The Journal of Medicine and Philosophy 22(3): 213-217.

  • ––––– 1997b. The best-interests standard as threshold, ideal, and standard of reasonableness. The Journal of Medicine and Philosophy 22(3): 271–289.

  • ––––– 2004a. Minimal risk as an international standard in research. Journal of Medicine and Philosophy 29(3): 351–738.

  • ––––– 2004b. What conditions justify risky nontherapeutic or “no benefit” pediatric studies: A sliding scale analysis. Journal of Law, Medicine & Ethics 32(4): 749–758.

  • ––––– 2007. The best interests standard for incompetent or incapacitated persons of all ages. The Journal of Law, Medicine & Ethics 35(1): 187–196.

  • ––––– 2012. On justifying pediatric research without the prospect of clinical benefit. The American Journal of Bioethics 12(1): 32–34.

  • Levine, R.J. 1988. Ethics and regulation of clinical research, 2nd ed. New Haven: Yale University Press.

  • ––––– 2008. The nature, scope, and justification of clinical research: What is research? Who is a subject? In The Oxford textbook of clinical research ethics, edited by E.J. Emanuel, C.C. Grady, R.A. Crouch, R.K. Lie, F.G. Miller, and D.D. Wendler, 211-221. New York: Oxford University Press.

  • London, A. 2006. Reasonable risks in clinical research: A critique and a proposal for the Integrative Approach. Statistics in Medicine 25(17): 2869–2885.

  • Luchtenberg, M., E. Maeckelberghe, L. Locock, L. Powell, and A.E. Verhagen. 2015. Young people’s experiences of participation in clinical trials: Reasons for taking part. The American Journal of Bioethics 15(11): 3–13.

  • Millum, J., D. Wendler, and E.J. Emanuel. 2013. The 50th anniversary of the Declaration of Helsinki: Progress but many remaining challenges. JAMA 310(20): 2143–2144.

  • Morris, K. 2013. Revising the Declaration of Helsinki. The Lancet 381: 1889–1890.

  • National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1977. Research involving children. Besheda, MA. https://repository.library.georgetown.edu/bitstream/handle/10822/559373/Research_involving_children.pdf#page=1. Accessed December 18, 2020.

  • Nelson, R.M., and L.F. Ross. 2005. In defense of a single standard of research risk for all children. The Journal of Pediatrics 147(5): 565–566.

  • Parker, C. 2010. The moral primacy of the human being. Journal of Medical Ethics 36(9): 563–566.

  • Pattinson, S.D. 2012. Emergency research and the interests of participants. Medical Law International 12(2): 121–141.

  • Piasecki, J., M. Waligora, and V. Dranseika. 2015. Non-beneficial pediatric research: Individual and social interests. Medicine, Health Care and Philosophy 18(1): 103–112.

  • Rawls, J. 1999. A theory of justice, revised ed. Cambridge, MA: Belknap Press.

  • Resnik, D. 2005. Eliminating the daily life risks standard from the definitione of minimal risk. Journal of Medical Ethics 31(1): 35–38.

  • Redmon, R.B. 1986. How minors can be respected as ends yet still be used as subjects in non-therapeutic research. Journal of Medical Ethics 12(2): 77–82.

  • Rid, A. 2012. Risk and risk-benefit evaluations in biomedical research. In Handbook of risk theory. Epistemology, decision theory, ethics, and social implications of risk, edited by S. Roeser, R. Hillerbrand, P. Sandin, and M. Peterson, 179-211. Springer Science+Business Media B.V.

  • ––––– 2014. Setting risk thresholds in biomedical research: Lessons from the debate about minimal risk. Monash Bioethics Review 32(1-2): 63–85.

  • Rossi, J. and R.M. Nelson. 2017. Minimal risk in pediatric research: a philosophical review and reconsideration. Accountability in Research 24(7): 407–432.

  • Różyńska, J. 2021. Taking the principle of the primacy of the human being seriously. Medicine, Health Care and Philosophy 24(4): 547–562.

  • Salter, E.K. 2012. Deciding for a child: A comprehensive analysis of the best interest standard. Theoretical Medicine and Bioethics 33(3): 179–198.

  • Shah, S. 2013. Does research with children violate the best interests standard? An empirical and conceptual analysis. Northwestern Journal of Law and Social Policy 8: 121–173.

  • Singer, P. 2011. When is research on children ethical? The Lancet 377(9760): 115–116.

  • Snyder, J., C. Miller, and G. Gray. 2011. Relative versus absolute standards for everyday risk in adolescent HIV prevention trials: Expanding the debate. The American Journal of Bioethics 11(6): 5–13.

  • Spriggs, M. 2012. Justifying pediatric research not expected to benefit child subjects. The American Journal of Bioethics 12(1): 42–44.

  • Staphorst, M., and S. van de Vathorst. 2015. Empirical data on benefits children experience in clinical research. The American Journal of Bioethics 15(1): 20–21.

    Article  Google Scholar 

  • Staphorst, M.S., J.A. Hunfeld, and S. van de Vathorst. 2017. Are positive experiences of children in non-therapeutic research justifiable research benefits? Journal of Medical Ethics 43(8): 530–534.

  • Sumner, L.W. 1996.Welfare, happiness, and ethics. Oxford University Press.

  • United Nations Educational, Scientific and Cultural Organization (UNESCO). 2005. Universal Declaration on bioethics and human rights. http://portal.unesco.org/en/ev.php-URL_ID=31058%26URL_DO=DO_TOPIC%26URL_SECTION=201.html. .

  • U.S. Code of Federal Regulations. 2018. U.S. 45 Code of Federal Regulations §46.102(j) (Subpart A: Basic HHS Policy for Protection of Human Research Subjects); §46.401–409 (Subpart D (Additional policy for children involved as subjects in research). https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=83cd09e1c0f5c6937cd9d7513160fc3f&pitd=20180719&n=pt45.1.46&r=PART&ty=HTML#se45.1.46_1102. Accessed December 18, 2020.

  • Wachbroit, R. 2012. On Wendler’s new justification for pediatric research. The American Journal of Bioethics 12(1): 40–42.

  • Waligora, M., K. Strzebonska, and M.T. Wasylewski. 2018. Neither the harm principle nor the best interest standard should be applied to pediatric research. The American Journal of Bioethics 18(8): 72-74.

  • Weijer, C. 2000. The ethical analysis of risk. The Journal of Law, Medicine & Ethics 28(4): 344–361.

  • Wendler, D. 2005. Protecting subjects who cannot give consent: Toward a better standard for minimal risk. Hastings Center Report 35(5): 37–43.

  • ––––– 2010. The ethics of pediatric research. New York: Oxford University Press.

  • ––––– 2012. A new justification for pediatric research without the potential for clinical benefit. The American Journal of Bioethics 12(1): 23–31.

  • Wendler, D. and L. Glantz. 2007. A standard for assessing the risks of pediatric research: Pro and con. The Journal of Pediatrics 150(6): 579–582.

  • Wendler, D., E. Abdoler, L. Wiener, and C. Grady. 2012. Views of adolescents and parents on pediatric research without the potential for clinical benefit. Pediatrics 130(4): 692–699.

  • Westra, A.E., J.M. Wit, R.N. Sukhai, and I.D. de Beaufort. 2011). How best to define the concept of minimal risk. The Journal of Pediatrics 159(3): 496–500.

  • Williams, G. 2012. Children as means and ends in large-scale medical research. Bioethics 26(8): 422–430.

  • World Health Organization (WHO). 1995. Guidelines for good clinical practice (GCP) for trials on pharmaceutical products. Geneva.

  • World Medical Association (WMA). 1975. Declaration of Helsinki. Recommendations guiding medical doctors in biomedical research involving human subjects. Tokyo, Japan. https://www.wma.net/wp-content/uploads/2018/07/DoH-Oct1975.pdf. Accessed December 18, 2020.

  • ––––– 2013. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Fortaleza, Brazil. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed December 18, 2020.

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This analysis was supported by a grant of the National Science Centre, Poland, no. 2014/15/B/HS1/03829.

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  1. Center for Bioethics and Biolaw, Faculty of Philosophy, University of Warsaw, Krakowskie Przedmiescie 3, 00-047, Warsaw, Poland

    Joanna Różyńska

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Różyńska, J. The Principle of the Primacy of the Human Subject and Minimal Risk in Non-Beneficial Paediatric Research. Bioethical Inquiry 19, 273–286 (2022). https://doi.org/10.1007/s11673-022-10179-7

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