Rethinking Research Ethics
Authors: Rosamond Rhodes
Journal: The American Journal of Bioethics (2010)

Abstract Contemporary research ethics policies started with reflection on the atrocities perpetrated upon concentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim of this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. Keywords: researchethicsvulnerableinformed consentautonomybeneficencesocial purpose ACKNOWLEDGEMENTS Preliminary work on this paper was presented as, "Rethinking Informed Consent for Research," at the International Bioethics Retreat, Florence, Italy, October 4, 1999, and a later, fuller version was read at Davidson College, November 5, 1999. I thank the members of those audiences for their comments. Iam also grateful to Joe Fitschen, Ian Holzman, Jonathan Rhodes, and AJOB's anonymous reviewers for their critical comments and suggestions. I am especially indebted to Karin Meyers for all that I have learned from our vigorous debates in our annual seminar on research ethics. This article originally appeared in The American Journal of Bioethics 5(1): 7–28. Notes Madison Powers identifies this focus on protecting the Marxist element. He sees it as "[t]he central thrust" in vulnerable from exploitation in research as an antiliberal research policy (Powers 1998, 151–152). Ezekiel J. Emanuel, D. Wendler, and C. Grady have similarly challenged the primacy of informed consent in current research policy, and they advocate for some of the changes in the research ethics framework that are similar to those that I recommend. Nevertheless, my route to these similar conclusions is significantly different. In several different forums, I have heard speakers describe "research ethics as standing firmly upon two pillars, informed consent and IRB review," or words to that affect. In a similar vein, Trudo Lemmens asserts, "if you are a North American bioethicist, everything looks like a problem of informed consent." (CitationLemmens 2001, 52) I would add that "if you are a North American bioethicist," the solution to every problem looks like another group that should be declared "vulnerable." There were a few notable exceptions: In 1900 Walter Reed obtained informed consent for his yellow fever experiments; 1900 regulations by the Prussian Ministry of Health required informed consent for nontherapeutic experiments; 1931 German regulations required informed consent for new therapy and experimentation. [Cf. CitationJonsen 1998b] CitationJonsen 1998b refers to 500 journal articles on research ethics written in the decade prior to 1963 (p. 7). Just what is being counted as a relevant paper or when they were published is not clear from Jonsen's remarks. Nevertheless, it does seem clear that the subject had received little attention before 1960. My own MED LINE/Pub Med search of English language articles revealed the following numbers of publications: Search on "ethics AND research": (1940–1949) 0; (1950–1959) 9; (1960–1969) 200; (1970–1979) 1688; (1980– 1989) 5834. Search on informed consent AND research: (1940–1949) 0; (1950–1959) 0; (1960–1969) 11; (1970–1979) 828; (1980–1989) 2254. The other two principles are: "(2) The danger of each experiment must have been investigated previously by means of animal experimentation; and (3) The experiment must be performed under proper medical protection and management." (Appelbaum et al. 1987, 212) These principles were significantly altered and expanded in the Nuremberg Code. The priority of principle 1 was preserved as The Code's principle #1. A weaker version of principle 2 became The Code's principle #3. Principle 3's interest in expertise appears in The Code's principle #8, but the original concern with oversight seems to disappear entirely. In this account I follow Appelbaum et al. 1987. Similar accounts are given by Advisory Committee on Human Radiation Experiments 1995; Annas et al. 1977; CitationBrody 1998; CitationFaden & Beauchamp 1986; CitationJonsen 1998b; CitationRothman 1991; CitationShamoo and Resnik 2003; CitationVeatch 1987; CitationSchmidt 2004; Vollman and Winau 1996. Parents should certainly protect their children. But, consider the bicycle-riding policy that parents would adopt if they took protection to be their primary parental responsibility. Children would not be allowed to ride bicycles because it would subject them to risk of harm. Yet, parents who actually allow their children to ride are likely to consider the importance of protection along with the importance of other developmental goals such as: independence, risk management, social interaction, exploration. When a multiplicity of goals is accepted, protection is considered in the context of other critical objectives and other aims will sometimes be overriding. Robert J. Levine takes a similar view of the history of research ethics. He too sees that beginning with a focus on Nazi atrocities has led to viewing research as dangerous and exploitive. Even more vigorous efforts to protect vulnerable subjects of research are urged by non-governmental groups such as the Alliance for Human Research Protection (AHRP). Again, Walter Reed was one of few notable exceptions who obtained informed consent from his research subjects. He also provided a $100 incentive for those enrolled in his yellow fever study and an additional $100 for those who contracted yellow fever as part of the study or a $200 benefit to a beneficiary in case of the subject's death from yellow fever. Furthermore subjects would forfeit these benefits by leaving the camp during the study period. These considerable inducements and constraints would be considered unethical according to today's reigning views of research ethics. Philip S. Hench Walter Reed Yellow Fever Collection, "English translation [from Spanish] of the Informed Consent Agreement for Antonio Benigno, November 26, 1900. (8/6/03) http://etext.lib.virginia. edu/etcbin/fever-browse?id = 07004001 E.g., the Universal Declaration of Human Rights, the recommendations of the National Bioethics Advisory Commission in the U.S. There is a long philosophic tradition of discussing autonomy along these lines. It begins with Aristotle and the Stoics and continues prominently in Hobbes, Kant, Mill, Berlin. In contemporary literature the concept is commonly discussed in terms such as "higher-order desires," "higher-order preferences," or "reflective endorsement." It is beyond the scope of this discussion to delve further into this rich and nuanced literature. Because Kant's account is the most frequent point of reference for discussions of autonomy in the bioethics literature, I employ Kantian terms in my account. The Canadian Tri-Council guidelines takes this view of "considering persons competent barring evidence to the contrary." The remaining five policies discussed in their paper, as well as their own position, recommend the opposite autonomy disparaging approach (CitationWendler and Prasad 2001, 12; CitationYoung 1998). CitationWendler and Prasad (2001) discuss what they see as a major failing of the current regulatory reliance on informed consent. They discuss six sets of guidelines that have been put forward to protect those who lack decisional capacity. As they see it, all of these guidelines advocate for making decisions on research participation that are "consistent with their [the subjects'] remaining preferences and interests." As I see it, except for subjects who previously explicitly expressed views on research participation, showing respect for remaining preferences and interests is incoherent because these inclinations do not flow from a self-legislating will. A decision on grounds of restoring or promoting autonomy takes the possibility of future autonomy into account where that may be possible. Concern for future autonomy could be a ground for restricting research participation, but it is a very different ground. Jonas's influence on contemporary research policy is acknowledged by Albert R. Jonsen. "The easy assumptions about social progress as a rationale to override human rights was thoroughly demolished (a famous essay by philosopher Hans Jonas contributed mightily to its fall)" (CitationJonsen, 1998b Sourcebook, 9). "We have, or think we have, a more significant luxury, of living in a world understood as a community of moral equals; we want to believe that what people deserve or are owed is determined not by considerations of social position but, at the most basic levels of morality, from a position of equality." (CitationWilliams 2002, 117). The parameters of due and undue inducements is an important topic in research ethics. Saying more here would go beyond the scope of this paper. Gerald Dworkin might classify this account of hypothetical consent to a research participation policy as a "collective decision" justification for hard paternalism (CitationDworkin 1983). I have presented this argument in the terms of contractarian constructivism that we find in CitationRawls (1993) and CitationScanlon (1998). I pointedly employ Rawlsian language and draw on his accounts of "rational" and "reasonable." This thought experiment is designed to illuminate responsibility for research participation. Issues related to the funding of research and research oversight, as well as the profits that we allow pharmaceutical companies to reap are acknowledged but bracketed. This "novel proposal" should be taken as a hypothetical construction for the sake of illustrating a point. An actual policy would have to take these and other important broad and detailed considerations into account. My novel proposal is far more modest. Every ten years is just a guesstimate. The number would, of course, be subject to debate based on data about the need for research participation. The frequency of required participation could be more or less frequent. Don Marquis alludes to "an ethics of conscription" in a paper where he wrestles with the incompatible commitments of treatment and research. Surrogates would select the research participation service for those who lacked the capacity to make the selection for themselves (e.g., children, the profoundly retarded). I intend my position to reflect a point that Jay Katz makes. He explains that a "thorough-going commitment to unequivical honesty in making disclosures to the subjects of research" should be coupled with "a willingness to abandon a contemplated research project if too many subjects do not volunteer after all alternatives, risks, and benefits have been explored with them" (CitationKatz 1992, 257). There is considerable debate about the decisional capacity of mature minors with some taking the position that "those age 14 and older, may have as well developed decisional skills as adults for making informed health care decisions" (American Academy of Pediatrics, Committee on Bioethics, Informed Consent, Parental Permission, and Assent in Pediatric Practice, Pediatrics 1995. Feb; 95(2):314–17). Others, particularly specialists in brain development and developmental psychology, have taken the position that decisional skills are only a piece of maturity and that full mental maturity is not achieved until much later. I tend to side with the latter group. Lainie Friedman CitationRoss (2002) argues for the place of parents in making decisions on behalf of children who are minors. In emergency situations (e.g., ruptured appendix) physicians override a surrogate's unreasonable refusal of treatment. In non-emergency situations, the physician may not simply override a surrogate's unreasonable refusal of treatment. Nevertheless, the physician has the responsibility of identifying a surrogate's unreasonable treatment refusal and, when the refusal is likely to have a serious impact on well-being, to bring the matter before the courts. Jonsen points out that "[f]rom Hippocrates' time to the nineteenth century, experimentation was not clearly distinguished from practice," (CitationJonsen 1998b, 5). Although the authors of The Belmont Report were specifically asked to draw a distinction between the two, the reason for marking the border is not clear. Perhaps those who made the request were following the 1964 Declaration of Helsiniki which discusses the importance of allowing doctors to innovate (Principle II, 1) and distinguishes therapeutic from non-therapeutic research (Sections II & III). Although policy separates the issues of research with children from issues of research with other subjects who lack decisional capacity, Brody suggests that these policies should be analogous (CitationBrody 1998, 131). This suggestion has been made in conversation by Daniel A. Moros. Parents who allow their children to ride bicycles may impose limitations that reflect a concern about protection from excessive or likely risks. Parents may restrict riding to bike paths and require children to wear helmets. Similarly, IRBs can impose limits on research or prohibit studies that expose subjects to excessive or likely significant risks. In its commitment to beneficence Helsinki follows physician Claude Bernard who discussed medical experimentation in his 1865 book on the subject (CitationBernard 1957). Here and throughout, for the sake of highlighting the policy move in the direction of beneficence, I refer to the 1989 version of the Declaration of Helsinki which appears in Jonsen, Veatch and Walters, 1998, pp. 13–15. The 1947 Nuremberg Code does not endorse beneficence. The Nuremberg Code expresses concern for he good of society (#2) and "the humanitarian importance" of the research (#6) as well as concern for avoiding "unnecessary… suffering and injury" (#4) and protecting subjects "against even remote possibilities of injury, disability, or death" (#7). If this principle of beneficence were applied to medical practice, blood and organ donation would be prohibited on grounds of causing harm without direct benefit to the donor. Furthermore, any physician who provided less than the maximal best treatment for patients, such as those who could not afford the very best or where resources (e.g., beds, equipment, medicine, time, energy) were scarce, would also be in violation of the principle. In other words, clinical medicine that is otherwise considered appropriate can frequently be taken to violate this understanding of the principle of beneficence. Similar arguments can be mounted about the importance of studying medical interventions in the elderly and pregnant women. Limitations on research imposed on everyone by regulations and IRB decisions would protect individuals from unreasonable harms. This paternalism would not be justified by protecting those who lack decisional capacity (i.e., what has been called "soft paternalism") but by the significant social benefit achieved by preserving the trustworthiness of biomedical science. In other words, this is an imposition on those who should be presumed to be autonomous, hence, "hard paternalism." The changes in IRB responsibility that I am suggesting would involve additional expertise, training, staffing, and monitoring to provide the appropriate level of review and oversight. The details of how these costs can be met goes beyond the scope of this discussion. For example, National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 1977. Research Involving Children. DHEW (OS)770004. U.S. Government Printing Office, Washington, DC. Recommendation 1 and Comment. Jay Katz makes a similar point. He writes, "Whereas such a fundamental reorientation will create formidable problems, it will not destroy the research enterprise.… Research subjects will continue to participate in research but they will do so now in a true collaborative spirit" (CitationKatz 1992, 258). The tradition of contractarian theory, from Hobbes to Rawls and Scanlon, employs hypothetical models of agreement, and not actual consent, to deduce just principles for regulating society. For example, those behind Rawls's veil of ignorance are hypothetical representatives of hypothetical persons or hypothetical representatives of hypothetical family lines. In this tradition it is legitimate to demonstrate that a principle is just without having actual consent.