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

Dresser R. , “Designing Babies: Human Research Issues,” IRB 26, no. 5 (2004): 1–8.

Moreno J. D. , Mind Wars: Brain Research and National Defense (Washington, D.C.: Dana Press, 2006).

Personal communication from Olivier Rabin, Director of Sciences, World Anti-Doping Agency, May 25, 2007.

Savulescu J. , “Justice, Fairness, and Enhancement,” Annals of the New York Academy of Sciences 1093, no. 1 (2006): 321–328, at 324

Johnson T. , “What Is 20/20 Vision?” available at <http://www.uihealthcare.com/topics/medicaldepartments/ophthalmology/2020vision/index.html> (last visited June 12, 2008).

Olshansky J. S. Hayflick L. Carnes B. A. , “Position Statement on Human Aging,” Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57, no. 8 (2002): B292–B297.

Apud J. A. Mattay V. Chen J. Kolachana B. S. Callicott J. H. Rasetti R. , “Tolcapone Improves Cognition and Cortical Information Processing in Normal Human Subjects,” Neuropsychopharmacology 32, no. 5 (May 2007): 1011–1020.

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).

Emanuel E. J. Wendler D. Grady C. , “What Makes Clinical Research Ethical?” JAMA 283, no. 20 (2000): 2701–2711.

Weijer C. Miller P. B. , “When Are Research Risks Reasonable in Relation to Anticipated Benefits?” Nature Medicine 10, no. 6 (2004): 570–573.

Freedman B. , “Equipoise and the Ethics of Clinical Research,” New England Journal of Medicine 317, no. 3 (1987): 141–145; Miller F. G. Rosenstein D. L. , “The Therapeutic Orientation to Clinical Trials,” New England Journal of Medicine 348, no. 14 (2003): 1383–1386.

See Belmont Report, supra note 8.

Wendler D. Miller F. G. , “Assessing Research Risks Systematically: The Net Risks Test,” Journal of Medical Ethics 33, no. 8 (2007): 481–486.

Morreim H. , “The Clinical Investigator as Fiduciary: Discarding a Misguided Idea,” Journal of Law Medicine & Ethics 33, no. 3 (2005): 586–595.

Weijer C. Shapiro S. H. 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.

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).

45 CFR §46.111(a)(3).

See Emanual , supra note 9.

Ceci S. J. Peters D. Plotkin J. , “Human Subjects Review, Personal Values, and the Regulation of Social Science Research,” American Psychologist 40, no. 9 (1985): 994–1002.

45 CFR §46.111(a)(2).

Personal Communication from Bradford Grey, March 19, 2007.

Most S. P. Alsarraf R. Larrabee W. F. Jr. , “Outcomes of Facial Cosmetic Procedures,” Facial Plastic Surgery 18, no. 2 (2002): 119–124.

Meningaud J. P. Benadiba L. Servant J. M. , “Depression, Anxiety and Quality of Life: Outcome 9 Months after Facial Cosmetic Surgery,” Journal of Cranio-Maxillofacial Surgery 31, no. 1 (2003): 46–50.

Bolton M. A. Pruzinsky T. Cash T. F. , “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. McCabe R. E. , “Measuring Outcomes in Aesthetic Surgery: A Comprehensive Review of the Literature,” Plastic and Reconstructive Surgery 111, no. 1 (2003): 481–482.

Levine R. J. , Ethics and Regulation of Clinical Research, 2nd ed. (New Haven: Yale University Press, 1998): At 42–51.

Furrow B. R. Greaney T. L. Johnson S. H. , Bioethics: Health Care Law and Ethics, 5th ed. (St. Paul, MN: Thomson/West, 2004): at 446.

Rawls J. , A Theory of Justice (Cambridge: The Belknap Press of Harvard University Press, 1971).

Daniels N. , Just Health Care: Studies in Philosophy and Health Policy (Cambridge: Cambridge University Press, 1985).

Brock D. W. Daniels N. , “Ethical Foundations of the Clinton Administration's Proposed Health Care System,” JAMA 271, no. 15 (1994): 1189–1196.

Barrett B. Brown R. Mundt M. , “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.

Agar N. , Liberal Eugenics: In Defence of Human Enhancement (Malden, MA: Blackwell, 2004): At 167–168.

Gretchen C. , “Sharper Image, Better Performance,” Wired, available at <http://www.wired.com/science/discoveries/news/2006/02/70154> (last visited June 16, 2008).

See Belmont Report, supra note 8.

Chatterjee A , “Cosmetic neurology - The Controversy over Enhancing Movement, Mentation and Mood,” Neurology 63, no. 6 (2004): 968–974.

President's Council on Bioethics, Beyond Therapy: Biotechonolgy and the Pursuit of Happiness, Washington, D.C., 2003, at 306.

Macer D. R. Akiyama S. Alora A. T. , “International Perceptions and Approval of Gene Therapy,” Human Gene Therapy 6, no. 6 (1995): 791–803.

Farah M. J. 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.

Parens E. , “Authenticity and Ambivalence: Toward Understanding the Enhancement Debate,” The Hastings Center Report 35, no. 3 (2006): 34–41.

Parens E. , “Is Better Always Good? The Enhancement Project,” The Hastings Center Report 28, no. 1 (1998): S1–S17.

Engelhardt H. T. , “Human Nature Technologically Revisited,” Social Philosophy and Policy 8, no. 1 (1990): 180–191.

Martin L. G. Schoeni R. F. Freedman V. A. , “Feeling Better? Trends in General Health Status,” Journal of Gerontology Series B, Psychological Sciences and Social Sciences 62, no. 1 (2007): S11–S21.

Breggin P. R. 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).

Mehlman M. J. Banger E. Wright M. , “Doping in Sports and the Use of State Power,” St. Louis University Law Review 50 (2006): 15–73.

Yesavage J. A. Mumenthaler M. S. Taylor J. L. , “Donepezil and Flight Simulator Performance: Effects on Retention of Complex Skills,” Neurology 59, no. 1 (2002): 123–125.

Berg J. , Informed Consent: Legal Theory and Clinical Practice (Oxford and New York: Oxford University Press, 2001).

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.

45 C.F.R. 46.

21 C.F.R. 50.

There are few exceptions to the documentation requirement; 46 C.F.R. 117.

45 C.F.R. 46.116(a).

Subpart B of the HHS guidelines.

Subpart C of the HHS guidelines.

Subpart D of the HHS guidelines and 21 C.F.R. 50.50.

45 C.F.R. 46.111(b).

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.

Simon C. Elder M. Kodish E. Siminoff L. , “Altruistic Discourse in the Informed Consent Process for Childhood Cancer Clinical Trials,” American Journal of Bioethics 6, no. 5 (2006): 40–47.

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).

See Berg , supra note 47, at 58–60.

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).

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.”64. There is a broader question about how to weight individual versus societal risks and benefits. This is addressed in greater detail elsewhere. Juengst E. Rubin D. , Taking the Long View: Should Downstream Social Risks Influence the Review of Biomedical Research with Enhancement Applications? (in preparation).

But see supra note 9; Emanuel's argument that nothing is really coercive.

Malick F. Howard J. Koo J. , “Understanding the psychology of the cosmetic patients,” Dermatologic Therapy 21, no. 1 (2008): 47–53.

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)

45 CFR 46.111(2).

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).

For a more complete discussion of deception research, see Levine R. , Ethics and Regulation of Clinical Research (Baltimore: Urban and Schwarzenberg, 1986): 221–228.

In one study, Mondafinil was given to alleviate “excessive sleepiness” associated with SWSD.

45 CFR 46.408(a)

There are other situations in which individual are “vulnerable,” but medical care is certainly one of the most significant.

National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants, 2001, at 85–92.

See Berg , supra note 47, at 288–290.

Current proposed guidelines expected.

45 CFR 46.111(a)(2).

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 Kubu Cynthia , “Stimulating Debate: Ethics in a Multidisciplinary Functional Neurosurgery Committee,” Journal of Medical Ethics 32, no. 2 (2006): 106–109.

See, e.g., Ditto , “Advance Directives as Acts of Communication: A Randomized Controlled Trial,” Archives of Internal Medicine 161, no. 3 (2001): 421–430.

For example, a woman's spouse or boyfriend is usually closely involved in making breast augmentation decisions. See, e.g., Bracaglia R. Fortunato R. 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. Tebbetts T. , “An Approach that Integrates Patient Education and Informed Consent in Breast Augmentation,” Plastic and Reconstructive Surgery 110, no. 3 (2002): 971–978.

See Simon , supra note 58.

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.

Singh Gurm H. 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.

Kaw E. , “Medicalization of Racial Features: Asian American Women and Cosmetic Surgery,” Medical Anthropology Quarterly 7, no. 1 (1993): 74–89.

Id., at 79.

See National Bioethics Advisory Commission, supra note 74.

Bokhari F. Mayes R. 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.

Spillman M. A. 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.