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Human Subjects Protections in Biomedical Enhancement Research: Assessing Risk and Benefit and Obtaining Informed Consent

Published online by Cambridge University Press:  01 January 2021

Maxwell J. Mehlman  and
Jessica W. Berg
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Extract

There are two critical steps in determining whether a medical experiment involving human subjects can be conducted in an ethical manner: assessing risks and potential benefits and obtaining potential subjects’ informed consent. Although an extensive literature on both of these aspects exists, virtually nothing has been written about human experimentation for which the objective is not to prevent, cure, or mitigate a disease or condition, but to enhance human capabilities. One exception is a 2004 article by Rebecca Dresser on preimplantation genetic modification — one of the most controversial enhancement technologies — in which she states, “Under existing research ethics principles, it would be unethical for investigators to perform modifications exposing embryos expected to develop into healthy children to significant risk in exchange for a possible physical or mental enhancement.” But Dresser does not explain why such an experiment would be unethical under existing principles, and her conclusion is not self-evident.

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Independent
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Journal of Law, Medicine & Ethics , Volume 36 , Issue 3 , Fall 2008 , pp. 546 - 559
Copyright
Copyright © American Society of Law, Medicine and Ethics 2008

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References

Dresser, R., “Designing Babies: Human Research Issues,” IRB 26, no. 5 (2004): 1–8.CrossRefGoogle Scholar
Moreno, J. D., Mind Wars: Brain Research and National Defense (Washington, D.C.: Dana Press, 2006).Google Scholar
Personal communication from Olivier Rabin, Director of Sciences, World Anti-Doping Agency, May 25, 2007.Google Scholar
Savulescu, J., “Justice, Fairness, and Enhancement,” Annals of the New York Academy of Sciences 1093, no. 1 (2006): 321–328, at 324CrossRefGoogle Scholar
Johnson, T., “What Is 20/20 Vision?” available at <http://www.uihealthcare.com/topics/medicaldepartments/ophthalmology/2020vision/index.html> (last visited June 12, 2008).+(last+visited+June+12,+2008).>Google Scholar
Olshansky, J. S., Hayflick, L., and Carnes, B. A., “Position Statement on Human Aging,” Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57, no. 8 (2002): B292–B297.CrossRefGoogle Scholar
Apud, J. A., Mattay, V., Chen, J., Kolachana, B. S., Callicott, J. H., and Rasetti, R. et al., “Tolcapone Improves Cognition and Cortical Information Processing in Normal Human Subjects,” Neuropsychopharmacology 32, no. 5 (May 2007): 1011–1020.CrossRefGoogle Scholar
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, April 18, 1979, available at <http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm> (last visited June 12, 2008); 46 CFR 46.111(a)(2); 21 CFR 312.42 (b)(i); 45 CFR 46.120(a).+(last+visited+June+12,+2008);+46+CFR+46.111(a)(2);+21+CFR+312.42+(b)(i);+45+CFR+46.120(a).>Google Scholar
Emanuel, E. J., Wendler, D., and Grady, C., “What Makes Clinical Research Ethical?” JAMA 283, no. 20 (2000): 2701–2711.CrossRefGoogle Scholar
Weijer, C. and Miller, P. B., “When Are Research Risks Reasonable in Relation to Anticipated Benefits?” Nature Medicine 10, no. 6 (2004): 570–573.CrossRefGoogle Scholar
Freedman, B., “Equipoise and the Ethics of Clinical Research,” New England Journal of Medicine 317, no. 3 (1987): 141–145; Miller, F. G. and Rosenstein, D. L., “The Therapeutic Orientation to Clinical Trials,” New England Journal of Medicine 348, no. 14 (2003): 1383–1386.CrossRefGoogle Scholar
See Belmont Report, supra note 8.Google Scholar
Wendler, D. and Miller, F. G., “Assessing Research Risks Systematically: The Net Risks Test,” Journal of Medical Ethics 33, no. 8 (2007): 481–486.CrossRefGoogle Scholar
Morreim, H., “The Clinical Investigator as Fiduciary: Discarding a Misguided Idea,” Journal of Law Medicine & Ethics 33, no. 3 (2005): 586–595.CrossRefGoogle Scholar
Weijer, C., Shapiro, S. H., and Cranley Glass, K., “For and against: Clincal Equipoise and Not the Uncertainty Principle Is the Moral Underpinning of the Randomized Controlled Trial,” BMJ 321, no. 7263 (2000): 756–758.CrossRefGoogle Scholar
Points to Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA Molecules into One or More Human Research Participants (Points to Consider), Appendix M-II-B-4, available at <http://www4.od.nih.gov/oba/rac/guidelines_02/Appendix_M.htm> (last visited June 12, 2008).+(last+visited+June+12,+2008).>Google Scholar
Id.Google Scholar
45 CFR §46.111(a)(3).Google Scholar
Id.Google Scholar
See Emanual, et al., supra note 9.Google Scholar
Ceci, S. J., Peters, D., and Plotkin, J., “Human Subjects Review, Personal Values, and the Regulation of Social Science Research,” American Psychologist 40, no. 9 (1985): 994–1002.CrossRefGoogle Scholar
45 CFR §46.111(a)(2).Google Scholar
Personal Communication from Bradford Grey, March 19, 2007.Google Scholar
Most, S. P., Alsarraf, R., and Larrabee, W. F. Jr., “Outcomes of Facial Cosmetic Procedures,” Facial Plastic Surgery 18, no. 2 (2002): 119–124.CrossRefGoogle Scholar
Meningaud, J. P., Benadiba, L., and Servant, J. M. et al., “Depression, Anxiety and Quality of Life: Outcome 9 Months after Facial Cosmetic Surgery,” Journal of Cranio-Maxillofacial Surgery 31, no. 1 (2003): 46–50.CrossRefGoogle Scholar
Bolton, M. A., Pruzinsky, T., and Cash, T. F. et al., “Measuring Outcomes in Plastic Surgery: Body Image and Quality of Life in Abdominoplasty Patients,” Plastic and Reconstructive Surgery 112, no. 2 (2003): 626–627; Ching, S., Thoma, A., and McCabe, R. E. et al., “Measuring Outcomes in Aesthetic Surgery: A Comprehensive Review of the Literature,” Plastic and Reconstructive Surgery 111, no. 1 (2003): 481–482.CrossRefGoogle Scholar
Levine, R. J., Ethics and Regulation of Clinical Research, 2nd ed. (New Haven: Yale University Press, 1998): At 42–51.Google Scholar
Furrow, B. R., Greaney, T. L., and Johnson, S. H. et al., Bioethics: Health Care Law and Ethics, 5th ed. (St. Paul, MN: Thomson/West, 2004): at 446.Google Scholar
Id.Google Scholar
Rawls, J., A Theory of Justice (Cambridge: The Belknap Press of Harvard University Press, 1971).Google Scholar
Daniels, N., Just Health Care: Studies in Philosophy and Health Policy (Cambridge: Cambridge University Press, 1985).CrossRefGoogle Scholar
Brock, D. W. and Daniels, N., “Ethical Foundations of the Clinton Administration's Proposed Health Care System,” JAMA 271, no. 15 (1994): 1189–1196.CrossRefGoogle Scholar
Barrett, B., Brown, R., and Mundt, M. et al., “Using Benefit Harm Tradeoffs to Establish Sufficiently Important Difference: The Case of the Common Cold,” Medical Decision Making 25, no. 1 (2005): 47–55, at 53.CrossRefGoogle Scholar
Agar, N., Liberal Eugenics: In Defence of Human Enhancement (Malden, MA: Blackwell, 2004): At 167–168.CrossRefGoogle Scholar
Gretchen, C., “Sharper Image, Better Performance,” Wired, available at <http://www.wired.com/science/discoveries/news/2006/02/70154> (last visited June 16, 2008).+(last+visited+June+16,+2008).>Google Scholar
See Belmont Report, supra note 8.Google Scholar
Chatterjee, A, “Cosmetic neurology - The Controversy over Enhancing Movement, Mentation and Mood,” Neurology 63, no. 6 (2004): 968–974.CrossRefGoogle Scholar
President's Council on Bioethics, Beyond Therapy: Biotechonolgy and the Pursuit of Happiness, Washington, D.C., 2003, at 306.Google Scholar
Macer, D. R., Akiyama, S., and Alora, A. T. et al., “International Perceptions and Approval of Gene Therapy,” Human Gene Therapy 6, no. 6 (1995): 791–803.CrossRefGoogle Scholar
Farah, M. J. and Wolpe, P. R., “Monitoring and Manipulating Brain Function: New Neuroscience Technologies and Their Ethical Implications,” The Hastings Center Report 34, no. 3 (2004): 35–45, at 43.CrossRefGoogle Scholar
Parens, E., “Authenticity and Ambivalence: Toward Understanding the Enhancement Debate,” The Hastings Center Report 35, no. 3 (2006): 34–41.Google Scholar
Parens, E., “Is Better Always Good? The Enhancement Project,” The Hastings Center Report 28, no. 1 (1998): S1–S17.CrossRefGoogle Scholar
Engelhardt, H. T., “Human Nature Technologically Revisited,” Social Philosophy and Policy 8, no. 1 (1990): 180–191.CrossRefGoogle Scholar
Martin, L. G., Schoeni, R. F., and Freedman, V. A. et al., “Feeling Better? Trends in General Health Status,” Journal of Gerontology Series B, Psychological Sciences and Social Sciences 62, no. 1 (2007): S11–S21.CrossRefGoogle Scholar
Breggin, P. R. and Breggin, G. R., Talking Back to Prozac: What Doctors Aren’t Telling You about Today's Most Controversial Drug (New York: St. Martin's Press, 1995).Google Scholar
Mehlman, M. J., Banger, E., and Wright, M., “Doping in Sports and the Use of State Power,” St. Louis University Law Review 50 (2006): 15–73.Google Scholar
Yesavage, J. A., Mumenthaler, M. S., and Taylor, J. L. et al., “Donepezil and Flight Simulator Performance: Effects on Retention of Complex Skills,” Neurology 59, no. 1 (2002): 123–125.CrossRefGoogle Scholar
Berg, J. et al., Informed Consent: Legal Theory and Clinical Practice (Oxford and New York: Oxford University Press, 2001).Google Scholar
Id. Informed consent may also have beneficial effects such as making participants more compliant with research since they will be fully informed of the requirements before agreeing to participate.Google Scholar
45 C.F.R. 46.Google Scholar
21 C.F.R. 50.Google Scholar
There are few exceptions to the documentation requirement; 46 C.F.R. 117.Google Scholar
45 C.F.R. 46.116(a).Google Scholar
Subpart B of the HHS guidelines.Google Scholar
Subpart C of the HHS guidelines.Google Scholar
Subpart D of the HHS guidelines and 21 C.F.R. 50.50.Google Scholar
45 C.F.R. 46.111(b).Google Scholar
Juengst, E., “Annotating the Moral Map of Enhancement: Gene Doping, the Limits of Medicine and the Spirit of Sport,” in Murray, T., ed., Ethics, Genetics and the Future of Sport: Implications of Genetic Modification Selection (Washington, D.C.: Georgetown University Press, in press). Expertise does not refer to the ability of a specific physician to do a specific kind of procedure, but instead to whether the intervention is part of the practice of medicine. Thus, we would not expect or require a traditional informed consent discussion in a situation where a physician happens to be offering haircut services to his patients. Physicians can claim no special expertise in offering haircuts (although perhaps the physician in question is also trained as a barber). The point is that when we imagine the paradigm situation in which informed consent operates, the assumption is that the intervention is one for which a physician has special expertise, and thus a physician has an ethical and legal obligation to provide information to the patient/subject about the intervention in question — this is one of the primary reasons for placing a disclosure obligation on the physician.Google Scholar
Simon, C., Elder, M., Kodish, E., and Siminoff, L., “Altruistic Discourse in the Informed Consent Process for Childhood Cancer Clinical Trials,” American Journal of Bioethics 6, no. 5 (2006): 40–47.CrossRefGoogle Scholar
In some sense, this is what is being argued in the debate about access to experimental drugs before FDA approval. Who should make the determination about whether the risks and potential benefits are worthwhile? See, e.g., Abigail Alliance for Better Access to Experimental Drugs v. von Eschenbach, 128 S. Ct. 1069 (2008).Google Scholar
See Berg, et al., supra note 47, at 58–60.Google Scholar
See, e.g., “FDA Breast Implant Consumer Handbook − 2004,” available at <http://www.fda.gov/cdrh/breastimplants/handbook2004/localcomplications.html> (last visited June 13, 2008).+(last+visited+June+13,+2008).>Google Scholar
For example, the INAMED breast implant brochure includes the following in the list of benefits: “may result in a more flattering, better proportioned figure, more clothing options, and may enhance your confidence and self-esteem.”Google Scholar
There is a broader question about how to weight individual versus societal risks and benefits. This is addressed in greater detail elsewhere. Juengst, E., and Rubin, D., Taking the Long View: Should Downstream Social Risks Influence the Review of Biomedical Research with Enhancement Applications? (in preparation).Google Scholar
But see supra note 9; Emanuel's argument that nothing is really coercive.Google Scholar
Malick, F., Howard, J., and Koo, J., “Understanding the psychology of the cosmetic patients,” Dermatologic Therapy 21, no. 1 (2008): 47–53.CrossRefGoogle Scholar
Jenkins, C., “Players Admit Steroids Changed Baseball,” USA Today, March 15, 2005, available at <http://www.usatoday.com/sports/baseball/2005-03-15-steroids-mlb-cover_x.htm> (last visited June 19, 2008)+(last+visited+June+19,+2008)>Google Scholar
45 CFR 46.111(2).Google Scholar
Consent requirement may also be altered under 45 C.F.R. 46.116(c), which refers to research studying public benefit programs. However, neither the exceptions in (c) nor (d) apply to research involving “nonviable neonates.” 45 CFR 46.205(c)(5).Google Scholar
For a more complete discussion of deception research, see Levine, R., Ethics and Regulation of Clinical Research (Baltimore: Urban and Schwarzenberg, 1986): 221–228.Google Scholar
In one study, Mondafinil was given to alleviate “excessive sleepiness” associated with SWSD.Google Scholar
45 CFR 46.408(a)Google Scholar
There are other situations in which individual are “vulnerable,” but medical care is certainly one of the most significant.Google Scholar
National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants, 2001, at 85–92.Google Scholar
Id.Google Scholar
See Berg, et al., supra note 47, at 288–290.Google Scholar
Current proposed guidelines expected.Google Scholar
45 CFR 46.111(a)(2).Google Scholar
For a discussion of some of the ethics issues raised by deep brain stimulation, including the role of famly decision makers see, e.g., Ford, Paul and Kubu, Cynthia, “Stimulating Debate: Ethics in a Multidisciplinary Functional Neurosurgery Committee,” Journal of Medical Ethics 32, no. 2 (2006): 106–109.CrossRefGoogle Scholar
See, e.g., Ditto, et al., “Advance Directives as Acts of Communication: A Randomized Controlled Trial,” Archives of Internal Medicine 161, no. 3 (2001): 421–430.CrossRefGoogle Scholar
For example, a woman's spouse or boyfriend is usually closely involved in making breast augmentation decisions. See, e.g., Bracaglia, R., Fortunato, R., and Gentileschi, S., “A Simple Way to Choose the Right Implant Volume in Breast Augmentation,” Aesthetic Plastic Surgery 29, no. 5 (2005): 407–408; Tebbetts, J. and Tebbetts, T., “An Approach that Integrates Patient Education and Informed Consent in Breast Augmentation,” Plastic and Reconstructive Surgery 110, no. 3 (2002): 971–978.CrossRefGoogle Scholar
See Simon, et al., supra note 58.Google Scholar
See National Bioethics Advisory Commission, supra note 74. Whether we have sufficient protections for economic vulnerability in the traditional research context is a question beyond the scope of this paper.Google Scholar
Singh Gurm, H. and Litaker, D. G., “Framing Procedural Risks to Patients: Is 99% Safe the Same as a Risk of 1 in 100?” Academic Medicine 75, no. 8 (2000): 840–842.CrossRefGoogle Scholar
Kaw, E., “Medicalization of Racial Features: Asian American Women and Cosmetic Surgery,” Medical Anthropology Quarterly 7, no. 1 (1993): 74–89.CrossRefGoogle Scholar
Id., at 79.Google Scholar
See National Bioethics Advisory Commission, supra note 74.Google Scholar
Bokhari, F., Mayes, R., and Scheffler, R. M., “An Analysis of the Significant Variation in Psychostimulant Use across the U.S.,” Pharmacoepidemiology and Drug Safety 14, no. 4 (April 2005): 267–275.CrossRefGoogle Scholar
Spillman, M. A. and Sade, R. M., “Clinical Trials of Xenotransplantation: Waiver of the Right to Withdraw from a Clinical Trial Should Be Required,” Journal of Law, Medicine & Ethics 35, no. 2 (2007): 265–272.CrossRefGoogle Scholar