APA Newsletters Volume 04, Number 1 Fall 2004
NEWSLETTER ON PHILOSOPHY AND MEDICINE FROM THE EDITORS, ROSAMOND RHODES AND MARK SHELDON
FROM THE CHAIR, DAVID DEGRAZIA "Philosophical Reflection and the President’s Council on Bioethics" OBITUARIES FRANKLIN G. MILLER "John Fletcher, In Memorial"
GREGORY PENCE "James Rachels, In Memorial" ARTICLES ROBERT E. GOODIN "Vulnerable Research Subjects" KENNETH KIPNIS "Vulnerability in Research Subjects" DOROTHY E. VAWTER AND KAREN G. GERVAIS "Reflections on Kipnis’s Concept of Medical Vulnerability"
TIMOTHY F. MURPHY "Presidents and their Right to Privacy" JENNIFER A. PARKS "A Call for Gender: Equity in Medical Tort Reform"

 

© 2004 by The American Philosophical Association ISSN: 1067-9464

APA NEWSLETTER ON
Philosophy and Medicine Rosamond Rhodes & Mark Sheldon, Co-Editors Fall 2004 Volume 04, Number 1
FROM THE EDITORS Once again, the Newsletter on Philosophy and Medicine is pleased to bring our readers an issue chock full of interesting papers. Presentations from the Pacific Division session on "Research Ethics and Human Vulnerability" sponsored by the Committee on Philosophy and Medicine are presented here as a group of papers. This collection of papers by Robert E. Goodin, Kenneth Kipnis, and Dorothy E. Vawter and Karen G. Gervais forms an important contribution to the literature on vulnerability in research. Also in this issue are papers on presidential privacy, race and ethnicity, and gender. These papers by Timothy F. Murphy, John R. Stone, and Jennifer A. Parks raise timely and challenging issues for bioethics in unusual terms. In sum, this issue offers a particularly fresh and engaging collection thoughtful papers on interesting issues. Robert E. Goodin’s piece on " Vulnerable Research Subjects" discusses two senses of vulnerability, one as a reason for action, another as a disqualifying condition. Goodin explains how both concepts factor into our thinking about biomedical research as well as medical treatment. He also discusses how subject vulnerability was transformed into the research ethics focus on informed consent and how the prominence of that principle has obscured other important concerns in the ethical conduct of research. Instead of focusing so closely on informed consent, Goodin proposes the concept of "autonomy interests" as a guide for research involving subjects who cannot provide informed consent. In his paper on " Vulnerability in Research Subjects," Kenneth Kipnis provides a novel approach to thinking about research subjects who are vulnerable. He explains seven different ways in which research subjects may be vulnerable. Kipnis suggests that rather than addressing specific subpopulations, rules for the ethical conduct of research should be sensitive to the varieties of vulnerability and focus on compensating strategies to address how the individual subjects may be vulnerable. Dorothy E. Vawter and Karen G. Gervais challenge Kipnis’s approach in their paper "Reflections on Kipnis’ Concept of Medical Vulnerability." Although they acknowledge that some of Kipnis’s suggestions are already incorporated into study design, they see others as aspirational standards. Furthermore, they object to some of Kipnis’s suggestions as subject inducements plans and where Kipnis finds subjects to be vulnerable because of their impaired ability to comprehend risks and benefits, Vawter and Gervais argue that measures should be taken to minimize the distorting influence of the therapeutic misconception rather than providing compensation. Their most pointed criticism is that Kipnis’s calls for the maximization of therapeutic benefit undermines the crucial research agenda. Timothy F. Murphy takes us off to another subject in his discussion of "Medical Confidentiality and Presidential Families." This is a timely piece that addresses questions raised about the Reagan family’s lack of open discussion about details of President Reagan’s illness and their treatment decisions in the period after he lost decisional capacity. Murphy offers several important distinctions to help us address the scope of privacy and access to information about public figures. John R. Stone raises the white issue in his paper on "Race/ Ethnicity, Health Disparities, and Bioethics." In his words, philosophy and bioethics are certainly "white-dominated" fields. In his paper, Stone explains how seeing issues of racial and ethnic disparities can have a different significance when seen through the eyes of whites or the eyes of people from groups that have suffered health disparities and who have been the historical subjects of discrimination. Stone identifies structural and policy issues that whites may overlook and discusses how sensitivity to racism and ethnic bias can make a difference in our analysis and approach to health disparities. In her paper, "A Call for Gender Equity in Medical Tort Reform," Jennifer A. Parks discusses President Bush’s proposal to limit monetary awards for pain and suffering in medical tort cases. Parks takes the silicone breast implant cases as her illustrative example and uses it to discuss the justice of the Bush plan. She presents a compelling case that Bush’s petition encourages corporate negligence, places undue burdens on plaintiffs, and disadvantages women. We want to be able to provide our readers with similarly rich issues in the future. So, we remind you to please send along your announcements, letters, papers, case analyses, poetry, and stories. Please feel free to volunteer a book review. Your contributions and queries should be sent to Rosamond or Mark at the addresses below. Please include your phone and fax numbers and email address. Rosamond Rhodes Box 1108 Mount Sinai School of Medicine One Gustave Levy Place New York, NY 10029 Phone: 212-241-3757; Fax: 212-241-5028 Email: rosamond.rhodes@mssm.edu Mark Sheldon Department of Philosophy and Medical Ethics and Humanities Program Northwestern University Evanston, IL 60208 Phone: 847-328-2739 Email: sheldon@northwestern.edu
FROM THE CHAIR
Philosophical Reflection and the President’s Council on Bioethics
David DeGrazia George Washington University When President Bush appointed the President’s Council on Bioethics in Januar y, 2002, some within the bioethics community expressed dismay about the PCB’s membership. The new committee was long on conservative credentials and short on expertise in bioethics, according to the critics. How could the PCB, they rhetorically asked, represent expertise in bioethics when only a minority of its members could boast scholarly credentials in this field? Weren’t the appointments more a reflection of the President’s conservative agenda than a reflection of the face of American bioethics? Representing such concerns, Jonathan Moreno—a well-respected philosopher-bioethicist at the University of Virginia and one of the more liberal scholars invited to serve—rejected the invitation. Charges of a political agenda driving committee membership resurfaced last year when two PCB members, Elizabeth Blackburn and William May, were quietly dismissed and replaced by scholars holding views more in line with Chair Leon Kass and the President himself. Behind Kass’s energetic leadership, the PCB has so far published five reports: Human Cloning and Human Dignity (July 2002), Beyond Therapy: Biotechnology and the Pursuit of Happiness (October 2003), Being Human: Readings from the President’s Council on Bioethics (December 2003), Monitoring Stem Cell Research (January 2004), and Reproduction and Responsibility: The Regulation of New Biotechnologies (March 2004). Having read three of these publications, I have found them well-written, erudite, very intelligent, and relatively courageous in exploring difficult ethical terrain and frequently challenging liberal "received wisdom" in bioethics. Coming from me, this is no trivial compliment because my moral judgments tend to be more in line with this liberal mainstream than with the President and PCB majority opinion. Even those far more critical of the PCB than I am must acknowledge that its work is addressing some of the most important forward-looking bioethical issues of our day. Apparently agreeing with this sentiment, the American Society for Bioethics and Humanities has set up a panel, consisting mostly of PCB members, to discuss the report Beyond Therapy in the ASBH’s annual meeting next October. While biotechnological enhancement is an important, timely issue, embr yonic stem cell research (ESCR) is, if anything, even more pressing. After Ronald Reagan’s death last June, following years of suffering from Alzheimer ’s disease—which many researchers believe ESCR holds special promise in treating—Nancy Reagan reinvigorated political discussion by publicly calling upon President Bush to relax restrictions he imposed on ESCR in the U.S. In an effort to draw a principled, pro-life line that was reasonably responsive to consequentialist concerns about research progress, Bush had on August 9, 2001 issued an executive order restricting federal funding for ESCR to research using stem cell lines created prior to the time of his order; no further embryos, not even those left over in fertility clinics and destined to disposal, could be "sacrificed" for federally funded research. Will Bush revise his position and, with it, American public policy? More importantly from an ethical standpoint, should he? Confident in philosophy ’s ability to illuminate such difficult problems as those identified here, the APA’s Committee on Medicine and Philosophy has established a panel entitled "The President’s Council on Bioethics: Political Legitimacy and the Report on Stem Cell Research," for the upcoming Eastern Division Meeting in Boston. Alfonso Gomez-Lobo of Georgetown University, a member of the President’s Council who has recently published on ESCR, will open by discussing ethical issues raised by this research—presenting his own views rather than attempting to speak for the entire PCB. Hilary Bok of Johns Hopkins University, a respectful critic of the PCB report in question, will challenge some of its reasoning. Leslie Francis, of the University of Utah, and Timothy Murphy, of the University of Illinois in Chicago, will take up questions concerning the PCB’s political legitimacy and representation of American bioethics in addressing such issues as ESCR. The Committee on Medicine and Philosophy looks forward to an open, vigorous yet respectful, and rewarding discussion of these issues by the panelists and members of the audience.
OBITUARIES
John Fletcher, In Memorial
Franklin G. Miller, Ph.D. National Institute of Health John Fletcher was one of the pioneers of bioethics, who helped create the way of thinking and the set of practices that we call bioethics. His reach within bioethics was wide and deep. John created an institutional presence for bioethics within the NIH Clinical Center—a daunting task which he pursued for 10 years, starting in 1977. Then he founded and developed a leading bioethics center at the University of Virginia. Perhaps his most important contributions were in scholarship relating to the ethics of reproductive technologies, conceptualizing and editing one of the major textbooks in clinical ethics, and zealously promoting hospital ethics programs, including ethics committees, ethics consultation services, and ethics education. John carried his religious vocation into the world of bioethics, leading the way for others and building communities of professionals dedicated to promoting moral reflection and moral conduct in the areas of medical research and medical care. What was it about John that moved people to share his passion for bioethics? It wasn’t his scholarship, though he was a very productive and influential scholar. It wasn’t his teaching, though John was a talented teacher. It was the strength of his personality, which had a gravitational force that drew others into his orbit and to the shared vocation of bioethics. I certainly would never have come to bioethics as a career at age 42 had I not been drawn in by the force of John’s personality, and by his dedication and commitment to make a difference in the climate of clinical medicine and research. John’s greatest strengths lay in reaching out to others to encourage them to join the bioethics movement and to contribute as teachers, ethics consultants, ethics committee members, and as scholars. He was a valued mentor to many bioethicists and clinicians interested in ethical issues. For those of us in the second generation of bioethicists, it is hard to imagine what it was like to bring bioethics into the clinical setting. In the words of David Rothman, John Fletcher was one of the "strangers at the bedside" who opened up the medical world to scrutiny from a moral perspective grounded in the rights of patients and research subjects. He made it less strange for those who followed in his footsteps. John, I believe, would not want us to look back on his life with rose-colored glasses. Like all of us, he had his weaknesses alongside his strengths. As Kant famously said, "Out of the crooked timber of humanity, nothing straight was ever made." John had a keen sense of his own fallibility. He learned how to navigate as an ethics consultant, called in to help resolve emotionally charged moral disputes, by jumping in, trusting his judgment, and making mistakes. Reflecting on mistakes was an opportunity for learning how to do it better. John invited criticism; he listened to it, and took it to heart. John liked to quote a saying of Paul Ramsey, another bioethics pioneer with whom he often disagreed, "The room for improvement is the biggest room in the house." John will not be forgotten by those who had the good fortune of feeling the gravitational force of his charismatic personality and witnessing his visionary leadership.
James Rachels, In Memorial
Gregory Pence University of Alabama at Birmingham James Rachels died from cancer on September 5, 2003 at age 62. A native of Georgia, Jim was graduated from MercerUniversity and earned his Ph.D. at the University of North Carolina. He then taught at Duke University, the University of Richmond, and on the graduate faculties of both New York University and the University of Miami. At NYU in the early 1970s, he was associated with a small group of philosophers who started the seminal New York chapter of the Society for Philosophy and Public Affairs, a group that included Tom Nagel and visiting scholars Peter Singer and Derek Parfit. In 1977, Jim became chair of Philosophy at the University of Alabama at Birmingham, rising three years later to become Dean of Arts & Humanities from 1978-1983, then had a one-year stint as acting Academic Vice President, after which he became University Professor. Jim had a special talent for elucidating complex philosophical issues in deceptively clear language. His early book, Moral Problems, was one of the first anthologies in the new field of applied ethics and in its first three years sold over a hundred thousand copies. According to his publisher, McGraw-Hill, his most well known book, The Elements of Moral Philosophy this year will sell more copies than any other philosophy text, and will be used in one third of ethics classes in North America. McGraw-Hill will posthumously publish Jim’s newly completed Introduction to Philosophy. Jim’s paper, "Active and Passive Euthanasia," was the first piece published by a moral philosopher in the New England Journal of Medicine (1975). Today it is still one of the most-reprinted articles in ethics, having been reprinted to date over 300 times. As the New York Times said in its extensive obituary, the piece "ignited" a debate over euthanasia, and "helped start an applied ethics movement in philosophy." This seminal piece, along with others by Judith Thomson and Peter Singer, gave philosophers issues to talk about in class that had philosophical heft. His book The End of Life: Morality and Euthanasia (Oxford, 1986) defended humane, humanistic treatment of standards of death and dying. His Created from Animals argued that modern ethics should pay more attention to similarities between human and non-human animals, rather than rigidly separate the two. In Can Ethics Provide Answers? (1997), he reprinted a dozen of his 60 essays from many journals, ones he thought would stand the test of time. He also edited seven books and served as a referee for several academic journals. Although his writings defended radical positions, in person he was neither confrontational nor an activist, preferring to let his writings do this work. More than anything else, he loved doing philosophy and being a philosopher. In the last months of his life and on the last day of his life, he was writing philosophy, finishing last bits and pieces. Near his last day, he told his sons that, for the first time in his life, he had no unfinished projects in philosophy. He is survived by his wife of forty years, Carol, and his two sons, David, an English professor at VMI, and Stuart, a philosophy professor at the University of Alabama in Tuscaloosa, his two grandchildren, and in Georgia, his parents and two sisters. The UAB Philosophy has started the Rachels Visiting Scholar Endowment Fund to honor Jim’s life. Contributions for it may be sent to: Philosophy, 900 13th Street South, Birmingham, AL 35294-1260.
ARTICLES
Vulnerable Research Subjects*
Robert E. Goodin Australian National University My concern here is with the vulnerabilities of people who are "objects of medical interventions." I mean for that term to extend to "patients" in the case of therapeutic interventions as well as to "subjects" in the case of experimental interventions. The latter are the official focus of my discussion, but reflecting on cognate cases of vulnerable patients in therapeutic settings sheds useful light on the case of vulnerable research subjects It is the vulnerability of agents to other agents that most concerns me here (although I shall also, of course, be tangentially concerned with the various conditions that make them vulnerable to one another1). In general, one agent is "vulnerable" to another insofar as the interests of the former are sensitive to the actions and choices of the latter.2 In a therapeutic setting, the patient’s vulnerability is largely (if not exclusively) to the attending physician. In an experimental setting, the subject’s vulnerability is (again, largely if not exclusively) to the researcher.
I. Vulnerability’s Two Faces Considerations of vulnerability might enter into bioethical reflections in two quite different ways. First is a broadly "consequentialistic" way, as in Goodin’s 3 Protecting the Vulnerable. By definition, if Sam is particularly vulnerable to Dr. Sue, then Sam’s interests are highly sensitive to Dr. Sue’s actions and choices. It therefore automatically follows that for any ethical theor y which attaches moral importance to promoting people’s interests, there is a moral reason for Dr. Sue to be particularly attentive to how her actions and choices will impact Sam’s interests. (Of course that reason is defeasible: there might be other stronger reasons for Dr. Sue to do something else.) That moral reason is stronger the more strongly—and, we might add, the more uniquely—Dr. Sue’s actions and choices are capable of affecting Sam’s interests. On this broadly "consequentialistic" account, Sam’s vulnerability (the potential impact of Dr. Sue’s actions and choices on Sam’s interests) is a reason for Dr. Sue to do something. Perhaps we might characterize that as a "responsibility" (or even perhaps a "duty"), derived from those consequentialistic considerations concerning Sam’s vulnerability to her. But for now, we can just leave it, more non-committally, as a "moral reason." A second way in which "vulnerability" might figure is as an exception or "disqualifying condition" within a broadly "deontological" conception of bioethics. On this model, we must above all respect the human dignity and moral autonomy of those with whom we deal. For medical practitioners and researchers, this is done by (among other things) securing "informed consent" from patients or subjects for procedures performed on them.4 Of course, there are many ways of telling a deontological tale. But because my concern here is with how vulnerability enters the picture, I shall focus on what I will call a "hard-line" version of the deontological ethic that makes informed consent a necessary if not sufficient condition of permissible medical interventions.5 "Vulnerability" enters into that sort of a consent-based deontological model as a disqualifying condition. "Vulnerabilities" of various sorts render agents incapable of giving meaningful consent to having those medical or experimental procedures performed on them. In the limiting case, vulnerable agents might not be able to consent at all— their vulnerability might be such as to deprive them of agency altogether. Here, however, I am going to focus on less extreme cases. These are cases in which vulnerable agents are still capable of giving what seems to be consent, but in which we are unsure of the moral value of that consent. The worry is that their vulnerability renders their putative consent "tainted," rather like a coerced confession in a criminal court or an agreement obtained by force or fraud in the law of torts. Where agents are sufficiently vulnerable, their putative consent might count for naught.6
II. If Not Consent, What? What follows when someone is not capable of meaningfully consenting to, or meaningfully withholding consent from, some intervention? Well, within a hard-line deontological ethic in which consent is the only right-maker, the upshot would be clear. If we do not have the permission of the person (or his or her authorized agent) to intervene in ways impinging his or her moral prerogatives, then we have no right to so intervene. This is as true of someone whose capacity to consent is compromised as it is of someone who is capable of consenting but who willfully withholds consent: in neither case do we have any right to so intervene, if consent is the only right-maker. Why a moral agent does not consent does not matter; the sheer absence of consent is all that matters in morally blocking our action. I hasten to add that this is a much harder-line deontological ethic than is embodied in any actual code of medical ethics. It seems so extreme as to preclude surrogate decisions for incapacitated patients, by anyone except perhaps their legally authorized representatives.7 In that and many other less extreme ways, this hard-line deontological ethic is very unlike any actual code of medical ethics operative anywhere in the world.8 Still, when excavating the true moral groundings for the ethical codes operative among us, it pays to begin by first exploring the limiting cases like this. This hard-line deontological ethic that treats consent as the only right-maker is especially interesting to explore in the context of the ethics of human experimentation, because at first brush, that looks like the ethic dominating thinking. The first "Directive for Human Experimentation" embodied in the Code laid down by the Nuremberg Tribunal specifies that: The voluntar y consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision.9 In short, at least at first brush: No consent, no experiment—on pain of something akin to practicing Nazi medicine. And insofar as the notion of vulnerability points to conditions invalidating consent, it thus provides what Ken Kipnis calls "a checklist of circumstances that...can invalidate the permissibility of research."10 But of course experimental settings are hardly the only ones in which doctors find themselves confronted with people who are vulnerable. Let us shift our focus to a therapeutic setting—a comatose patient who will die without urgent surgery, let’s say. There, "no consent, no intervention" would not be a sensible policy; certainly it is not the practice generally adopted in Emergency Rooms. There, after quickly checking the patient’s wallet and trying to contact the next of kin for instructions, the attending physician properly proceeds with whatever treatment "best medical practice" dictates in the circumstances— "as if " s/he had the patient’s informed consent, even though s/he does not. So too, upon reflection, should the experimenter. Indeed, the provisions of the US Code of Federal Regulations governing "Informed Consent of Human Subjects" now makes explicit provision for granting an "exception from informed consent requirements for emergency research."11 In certain tightly circumscribed conditions, experimental procedures that "hold out the prospect of direct benefit to the subjects" may be permitted on people from whom consent could not possibly be obtained ahead of time. One example was an experiment locating defibrilators in airports, to be used by laypersons on people having heart attacks before medics arrived, to see if that helped save lives: it was accepted by those authorizing that experiment that it was simply infeasible to obtain reliably informed consent from people in the midst of a heart attack; and since there was good reason to think that heart attack victims could benefit from those interventions, the experiment was authorized despite the fact that informed consent could not be obtained.12 Our concern here is with a medical researcher confronted with vulnerable subjects, and our question is, "What, then, follows from the fact that some subjects are "vulnerable" in ways that undermine their capacity to give or withhold meaningful consent for experiments to be practiced upon them?" The proper conclusion is not that we ought necessarily exclude them from our experiments—any more than in the "waived consent" cases we should exclude those who could benefit substantially from participation in the experiments, just because they cannot give informed consent. Rather, what follows is that we should apply "special scrutiny" to the conditions of their participation. Note, for example, the phrasing of the World Medical Association’s Helsinki Declaration: "When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent relationship to him or her or may consent under dures."13 Just as Emergency Room physicians performing emergency procedures on comatose patients are supposed to think in terms of what those patients would "have good reason" to consent to, so too ought experimenters confronted with subjects whose seeming "consent" is compromised by their vulnerability pay special attention to whether those subjects would "have good reason" to consent, were it not for those vulnerabilities.14 This is sometimes expressed in terms of "hypothetical consent." That can be an evocative way of calling to mind the reasons people might have for consenting. But what it provides us with is a window onto the agent’s reasons, not a warrant rooted in the agent’s will. Hypothetical consent is no kind of consent at all, as generations of students have been rightly taught to scoff when confronted with "just so" stories of a "social contract."15 If the hard-line deontological model is correct, and consent is the only possible right-maker for interventions of this sort, then it is actual consent that is morally required to do the trick. If the prime moral directive is to respect the other’s moral agency and moral autonomy, then actual rather than merely hypothetical consent is the only moral warrant that there can be for intervening into the sphere of someone else’s proper moral prerogatives. For us to acquire a right to operate on (or experiment on) people whose actual consent is morally questionable, we have to move away from that hard-line deontological model toward a more consequentialistic one, which takes due account of vulnerabilities in its own peculiar way.
III. Consent in Consequential Context I take it that neither of the polar forms of ethics, deontological or consequentialistic, is altogether tenable in a health-care context. A hard-line deontological ethic would, as I have just been arguing, deprive us of the ability to treat emergency room patients clearly in need of medical attention but incapable of consenting to the procedures. Conversely, a hard-line consequentialistic ethic might risk turning us into Nazi physicians, practicing procedures on people who clearly (but, we have good medical reason to believe, wrongly) refuse to consent. In searching for a hybrid, my own inclination is to build on consequentialist foundations, grafting consent-based considerations onto that. Here, in brief, is the strategy I would propose. Recall the consequentialist story I told above, in which Sam’s vulnerability to the actions and choices of Dr. Sue gave moral reasons for Dr. Sue to be particularly solicitous of Sam’s interests in her actions and choices. All we need to get an element of consent into the picture is to recall that among those interests of which Dr. Sue is supposed to be solicitous are Sam’s "autonomy interests." Sam, like all moral agents, has an interest in being and being seen to be a self-governing agent capable of embracing and acting on reasons of his own. The reason Dr. Sue should, where possible, seek Sam’s consent to any procedure—even where she is sure it is one that best promotes all of Sam’s other interests—is that securing Sam’s consent is the only way also to protect his autonomy interests. This way of building autonomy interests in, alongside Sam’s other interests, has several advantages. It explains, in a way the hard-line deontological model cannot, why it might be all right to perform procedures on people incapable of consenting or whose consent is tainted by vulnerabilities of various sorts (their autonomy interests are not actually being overriden, insofar as they are not actually in play). It explains, perhaps better than any plausible variation on the hard-line deontological model can explain, why it is wrong for physicians to help kill anyone who genuinely wants to die, without further enquiries.16 (Presumably even those of us who would approve of physician-assisted suicide would ordinarily want the physician to ensure, for example, that the patient had a terminal illness rather than was merely "tired of living" or just was having a bad day.) There are many details left to be worked out with that hybrid model, to be sure.17 I do not want to belabour them here, however. Instead, I want merely to point out that something like that sort of hybrid is—contrary to what seems to be the common supposition—what actually lies at the heart of contemporary strictures surrounding the ethics of human experimentation. What the bioethics profession generally seems to remember as the rule of "the Nuremberg Code" is the first Directive, quoted earlier—the one that says "the voluntary consent of the human subject is absolutely essential." That is why we hear, so often, that "the Nuremberg Code’s foundational concern" is with "the concept of consent."18 That consent-based principle was undoubtedly of signal important to the Nuremberg Tribunal. After all, they listed that as their first Directive, and they elaborated on it at far greater length than any other item on their list. But what seems often to be forgotten is that the Nuremberg Tribunal did go on to list nine further Directives, only one of which has anything to do with the consent of the research subject.19 The other forgotten eight Directives of the Nuremberg Tribunal that are more consequentialistic in form are these20: The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study... The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. No experiment should be conducted where there is a priori reason to believe that death or disabling injury will occur... The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment. ... 8. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe... that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.21 Thus, while consent is of signal importance (as per Directive 1), consent is supposed to come only after a whole raft of consequential requirements have already been met.22 Essential though people’s consent may be to the ethical legitimacy of experimenting on them, those other background conditions are also equally essential. Consent is capable of transforming illegitimate experiments into legitimate ones, only when it is given against the background of all those other consequential conditions having also been satisfied. Upon reflection, this is surely unsurprising. After all, we would not let a surgeon perform an operation—even with the patient’s consent—unless there was some reason to think that the operation would do some good. (Presumably even with purely cosmetic surgery, we have to have good grounds for thinking that it will succeed, at least on its own terms, for it to be justifiable.) By the same token, we would not let an experimenter perform an experiment, even with the subject’s consent, if there were not evidence from animal experiments and so forth to suggest that the experiment might succeed. A subject’s fully-informed consent to experimental procedures that are unnecessary, incompetent, or gratuitously dangerous morally counts for naught. That—as much as the better-remembered principle that "the voluntar y consent of the human subject is absolutely essential"—is the law of Nuremberg. Of course, we would not want to proceed without first (if possible) obtaining the consent of the patient or subject, as well. We do not want to operate or experiment on unwilling subjects. But consequentialistic-style considerations constitute a prior hurdle. We do not want to perform operations or experiments on people without good reason to think that they will work, either. Why then, we might ask, is the issue about "consent" so much better remembered among medical ethicists? Well, recall for whom medical ethicists are principally writing: people at the medical coalface, which is to say, practitioners at the bedside. This is evident in, for example, the AMA’s "Principles of Medical Ethics": well over half of the nine guiding principles clearly pertain to relations between the doctor and his or her own specific patients. It is all the more evident in the Physician’s Oath prescribed by the World Medical Association’s "Declaration of Geneva," which has the physician avowing that "the health of my patient will be my first consideration."23 From the point of view of medical practitioners at the bedside—face-to-face with patient in therapeutic settings or subjects in experimental ones— the belief that "voluntary consent is absolutely essential" is indeed the thought that they should hold most firmly in mind. That is not because those other Nuremberg Directives (and their therapeutic equivalents) do not matter. It is merely because that is not where they matter. The bedside is not the place to meet those other requirements. They should have been (indeed, they have to have been) taken care of elsewhere, in planning the experiment or treatment regime. The bit of the Nuremberg Code that is uniquely the responsibility of a physician who is face-to-face with a patient or experimental subject is the bit about obtaining "voluntary consent." And given that it is practitioners at the bedside to whom codes of medical ethics are principally addressed, it is only right that that principle should be accorded heavy emphasis—heavier emphasis than it would be, if we were addressing instead (or even equally) planners of health care systems or designers of medical experiments.
IV. Vulnerabilitries against Vulnerabilities When cashing out our morals in the currency of vulnerability, it is important to remember that those research subjects who we nervously deem "vulnerable" in ways that might compromise their consent to the experiment are often "vulnerable" in other ways, too. Often, they are vulnerable in the sense of suffering from medical conditions that make them suitable subjects for the experiment. Such people are vulnerable, too, in the sense that existing medical treatments of their condition are less than completely satisfactory (we would not be doing the experiment, certainly not on them anyway, otherwise); and the new trial treatment might be an improvement. When experimental treatment is expected to have positive therapeutic effects for the experimental subject as well, we are in the happy position of being able to justify the procedure on therapeutic grounds alone, and to treat any experimental payoffs as wholly unintended by-products. Often we are not in this happy state, though: realistically, we know that the benefits will be wholly or principally for other patients who come later, suffering from the same condition, rather than the patient upon whom the experiment is being performed. Still, even in this less happy scenario, we have a case of vulnerability-versus-vulnerability—the vulnerability of the experimental subject, versus the vulnerability of those who stand to benefit from the experiment. In any systematic application of our duty to "protect the vulnerable," those potential gains to vulnerable agents must be borne in mind, alongside all those other concerns about risks of vulnerable people being ill-used in research. For a particularly striking example, consider the continuing controversy over the exclusion of elderly people from clinical trials of drugs and medical procedures deployed commonly on the elderly. The issue is nicely set out in 1997 Editorial in the British Medical Journal: Practitioners face a difficult paradox in prescribing for the elderly. Those aged over 65 comprise only about 14% of the population in most industrialised countries, yet they consume nearly a third of all drugs. Ample evidence indicates that, even in healthy elderly people, aging impairs the way the body handles drugs. In ill elderly people these changes can be exaggerated considerably. In an ideal world data from premarketing and postmarketing surveillance studies would describe how a drug is likely to affect older patients differently from younger ones. Unfortunately, rather than being oversampled in clinical trials, to reflect their distribution in the drug consuming population, elderly people are inadequately represented.24 In some cases, the design of the trial literally excludes people over a certain age, for no scientifically justifiable reason.25 Other times the elderly are not formally excluded but are radically underrepresented in clinical trials. A recent RAND study analyzing patient and trial characteristics for 59,300 patients enrolled in 495 National Cancer Institute trials from 1997 through 2000 found, tellingly, that while 61% of cancer patients were elderly, only 32% of participants in clinical trails were elderly.26 Clearly, this is bad science. Insofar as the elderly are major users of those drugs and procedures, and insofar as the elderly do not react to them in the standard way, physicians clearly need those clinical trials to give them more information about the reactions of the elderly. And that is the way the issue is typically presented. The AMA’s Code of Ethics instruction on "subject selection for clinical trials" says, for example, that "Inclusion and exclusion criteria for a clinical study should be based on sound scientific principles."27 The reasons that the elderly are so often excluded or underrepresented in clinical trials of drugs, even those to be used predominantly by the elderly, are many and varied. The BMJ Editorial points to some: The "old old" are a messy lot physiologically. They are far likelier than the young to have coexisting medical problems, for which they are likely to be taking other potentially interacting drugs. They also have the distressing property of being more likely in the middle of a trial to suffer an infarct of the heart or brain or simply to drop dead. They are bad news for the drug development process. Yet another reason is that the elderly often count among those who would qualify as "vulnerable" in various respects, from whom we therefore cannot obtain meaningful consent. They are more likely to suffer cognitive impairments associated with the aging, they are more likely to be institutionalized, and so on. In addition to the pragmatic and scientific issues, then, there are also these ethical issues in obtaining meaningful informed consent associated with conducting clinical trials on the elderly. Ethical worries about their vulnerability, too, get in the way of including the elderly in experiments, in ways we scientifically should. Instead of construing this as an issue of "ethics" versus "good science," however, we can see it as an issue of "ethics versus ethics." Indeed, the ethical considerations on both sides can be seen to be broadly of a cloth, insofar as both involve an attempt to "protect the vulnerable." On the one side, we need to protect vulnerable research subjects from ill-usage in the experimental procedure. On the other side, we need to protect vulnerable patients from being prescribed drugs that have not been adequately tested on populations relevantly similar to their own. Saying that "vulnerabilities are involved on both sides" does not, of course, automatically tell us where exactly the balance should be struck. But the problem of weighing the competing considerations is nonetheless rendered far more tractable by getting them both on the same scale. Of course, there can be no thought of press-ganging subjects into experiments literally against their will. Kipnis is surely right to say that "the wrong committed by experimenting on an unwilling subject is of far greater seriousness than the wrong committed by unjustifiable exclusion."28 But that is not what is being contemplated, here. What is in view here is a consenting subject, albeit one who is vulnerable in ways that make us worry about the quality of that consent. In deciding on balance whether to go ahead and include the subject in the experiment, those worries notwithstanding, the benefit in prospect to other vulnerable agents ought I suggest be one further consideration weighing in favor of proceeding— particularly where, as perhaps with the elderly, the great majority of other potential experimental subject of the relevant sort would be consenting under similarly compromised conditions.
V. Conclusion The problem I have been wrestling with is why we should hesitate to experiment or operate on people who are vulnerable in ways compromising their capacity to consent— but why it might be all right to go ahead, despite those hesitations. My own preferred solution is to introduce "autonomy interests" into a consequentialistic model, which imposes a general duty on all doctors (and all others) to protect the interests of those who are especially vulnerable to their actions and choices. Other philosophers no doubt would prefer more deontological foundations. To them, I offer this closing observation. If you think the Nuremberg Tribunal got it broadly right, then for an experiment to be permissible it has to be both "right" and "good." That is to say, the researcher not only has to have the consent of the experimental subject; she also has to have good grounds for thinking that some good will come of the procedure. To those taught to see deontology and consequentialism as mutually exclusive alternatives, this requirement that the experiment be "both right and good" constitutes an interestingly different hybrid. It bears pondering how many more situations, other than medical experimentation, might manifest that same structure.
References American Medical Association (AMA) (2001), "Principles of Medical Ethics"; available at www.ama-assn.orgama/pub/ categor y/2512.html (accessed Jan 2, 2004). American Medical Association (AMA) (2003), "Code of ethics"; available at www.ama-assn.org/ama/pub/category/8423.html (accessed Nov 7, 2003). Arvon, J. (1997), "Editorial: Including Elderly People in Clinical Trials: Better Information Could Improve the Effectiveness and Safety of Drug use," British Medical Journal, 315, 1033; available at: bmj.bmjujournals.com/archive/7115/7115e5.htm (accessed Nov.) Bayer, A. and W. Tadd (2000), "Unjustified Exclusion of Elderly People from Studies Submitted to Research Ethics Committee for Approval: Descriptive Study," British Medical Journal, 321, 992. Bugeja, G., A. Kumar and A. K. Banerjee (1997), "Exclusion of Elderly People from Clinical Research: A Descriptive Study of Published Reports," British Medical Journal, 315, 1059. Dworkin, R. (1974), "The Original Position," in N. Daniels (ed.), Reading Rawls, (New York: Basic Books). Goodin, R. E. (1985 ), Protecting the Vulnerable (Chicago: University of Chicago Press). Gurwitz, J.H., N.F. Col and J. Avorn (1992), "The Exclusion of the Elderly and Women from Clinical Trials in Acute Myocardial Infarction," JAMA, 268, 1417. Hobbes, T. (1651) Leviathan (London: Crooke). Kipnis, K (2001) "Vulnerability in Research Subjects: A Bioethical Taxonomy," in Ethical & Policy Issues in Research Involving Human Participants (Bethesda, Md.: National Bioethics Advisory Commission, 2001), vol. 2, 174-84; available at wwww.georgetown.edu/research/nrcbl/nbac/human/overvol2.html (accessed Nov 17, 2003). Kipnis, K (2003) "Seven Vulnerabilities in the Pediatric Research Subject," Theoretical Medicine & Bioethics. Kipnis, K. (2004) "Ethical Pitfalls in Waived-Consent Trials," OHRPSRA Conference, Waikiki, Feb 10, 2004. Lewis, J. H. et al. (2003), "Participation of Patients 65 years of Age or Older in Cancer Clinical Trials," Journal of Clinical Oncology, 27 (#7), 1383-9. Mill, J. S. (1859), On Liberty (London: Parker & Son). Nuremberg Tribunal (1949), "Directives for human experimentation," Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10 (Washington, D.C.: Government Printing Office), vol. 2, 181; available at ohsr.od.nih.gov/nuremberg.php3 (accessed Dec 28, 2003). Schuch, P. H. (1994), "Rethinking Informed Consent," Yale Law Journal, 103, 899. US Code of Federal Regulations (1996), "Informed Consent of Human Subjects," CFR, 21, 50.24; available at http://history.nih.gov/history/laws/21CFR50.24.html (accessed Feb 21, 2004). US Code of Federal Regulations (2001) "Protection of Human Subjects," CRF, 21, 50 ; available at http://history.nih.gov/history/ laws/21CFR50.24.html (accessed Feb 21, 2004). World Medical Association (1948), "Declaration of Geneva: physician’s oath," available at www.cirp.org/library/ethics/geneva (accessed Jan 2, 2004). World Health Association (1989), "Declaration of Helsinki" (1964, as amended 1975, 1983, 1989); available at ohsr.od.nih.gov/ helsinki.php3 (accessed Jan 2, 2004).
Endnotes * An earlier version was presented to the American Philosophical Association, Pacific Division, Pasadena, March 2004. I am grateful for comments there, particularly from Ken Kipnis and Jeff Blustein. These are the sorts of things catalogued most ably, for the experimental case, in Kipnis 2001; see further Kipnis 2003. Goodin 1985, ch. 5. Goodin 1985, 62-70, discussing doctor-patient relations alongside lawyer-client ones as instances of "professional responsibilities" more generally. Goodin (1985, 62-70) raises doubts about the parallel voluntaristic account of professional responsibilities of doctors toward their patients: there it is argued that the reason doctors have special responsibilities toward their patients is not because of any voluntarily self-assumed obligations but, rather, because patients’ vital interests are particularly vulnerable to their doctors’ actions and choices. Similar issues are raised as regards researchers and experimental subjects in H. Schuch1994. An alternative deontological ethic might for example make its prime directive "respect for persons," which is ordinarily manifested by securing their informed consent before undertaking any medical procedures on them, but can also be manifested in various other ways as well. But if we do not necessarily have to secure a person’s informed consent to a procedure, vulnerability compromising that person’s capacity to give meaningful consent is then not necessarily a problem. To see why vulnerability might be a problem, in deontological terms, we therefore need to focus on versions of deontological ethics that prioritize informed consent. Because, in Hobbes’s (1651, ch. 14) terms, the "sign" does not, in the case of such agents, "sufficiently argue their will." A hard-line deontological analysis would accommodate the latter case by literally equating the consent of a legally authorized representative with the consent of the person whose agent it is: when the agent consents, the person whose agent it is thereby consents. In the absence of that formal legal authorization, however, there seems to be no way on a hard-line deontological ethic for that transfer of agency to be affected. There is no plausible story that could be told about how, "when the surrogate decision-maker has consented, the person on whose behalf the decision is being made has thereby consented." Cf. World Health Association 1989, Principle 11. Nuremburg Tribunal 1949. Kipnis 2001, 177. US Code of Federal Regulations 1996. Kipnis 2004. World Health Association 1964, Principle 10 (emphasis added). That Principle goes on to say that, "In that case the informed consent should be obtained by a physician who is not engaged in the investigation and who is completely independent of this official relationship"; and the next Principle goes on to say that, "In case of legal incompetence, informed consent should be obtained from the legal guardian in accordance with national legislation. Where physical or mental incapacity makes it impossible to obtain informed consent, or when the subject is a minor, permission from the responsible relative replaces that of the subject in accordance with national legislation." Thus, for example, under each of the dimensions of "vulnerability" he discusses, Kipnis (2001, 178-9) proposes "measures researchers might take to address" the limitations those vulnerabilities imply for capacity for meaningful consent. In some cases, those measures are designed to make vulnerable people’s consent more meaningful (in the case of cognitive vulnerabilities, e.g., with "plain language consent forms" or "supplementary educational measures") and other times involve measures to make sure that vulnerable agents’ interests are protected, albeit not through the agency of those agents themselves (in the case of cognitive vulnerability again, through "the proper use of surrogates and advocates"). My favorite version remains Ronald Dworkin’s (1974, p. 18): "Suppose you and I are playing poker and we find, in the middle of a hand, that the deck is one card short. You suggest that we throw the hand in, but I refuse because I know I am going to win and I want the money in the pot. You might say that I would certainly have agreed to that procedure had the possibility of the deck being short been raised in advance. But your point is not that I am somehow committed to throwing the hand in by an agreement I never made. Rather you use the device of a hypothetical agreement to make a point that might have been made without that device, which is that the solution recommended is so obviously fair and sensible that only someone with an immediate contrar y interest could disagree. Your main argument is that your solution is fair and sensible, and the fact that I would have chosen it myself adds nothing of substance to that argument." 1 6 "If I consent to your killing me, you would not thereby be permitted to do so. That some deed is okay with me does not always mean it is okay," as Kipnis (2001, 176) observes. The best stor y hard-line deontologists can tell here, presumably, is akin to Mill’s (1859, ch. 5) argument against slavery contracts: respect for autonomy does not oblige us to respect autonomous choices to extinguish autonomy, whether by selling oneself into bondage or by killing oneself either. That would oblige physicians to engage in the cruel prolongation of a terminal patient’s autonomous existence, however painful and ultimately pointless, contrary to the patient’s clear and rational preference for a more dignified end of his choosing. Many hard-line deontologists will reply "quite so" to that proposition, of course; but the reference to "dignity" in that case description might give pause to at least some deontologists who see respect for persons as being linked as much to "human dignity" as it is to "moral autonomy." Especially, perhaps, the worr y that other interests can outweigh autonomy interests too easily and often, if autonomy is seen as just one interest among many. Unless we make autonomy interests lexicographically prior to all others, we will be unable to satisfy those who demand that no medical procedures could ever be performed without the consent of a person who is actually capable of granting or withholding consent. Kipnis 2001, 176. Nuremburg Tribunal (1949, Directive 9) requires that, "During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible." "Forgotten" in the literature of medical ethics, if not the practice of IRBs, where it is standard practice to subject proposals first to a consequential-style risk-benefit calculus and then an informed consent test. Nuremburg Tribunal 1949. See similarly World Health Association (1964), whose Basic Principles 1-8 correspond broadly to the Nuremberg Tribunal (1949) directives above, with Principles 9-12 pertaining to issues of informed consent. Similar conditions to those quoted above are written into the provisions of the US Code of Federal Regulations, both pertaining to protection of human subjects in general and to the waived-consent experiments discussed above (US Code of Federal Regulations 2001 and 1996 respectively). Note that I describe these considerations as "consequential" or "consequentialistic in form" —by which I just mean "outcome-oriented." Why those should matter is, of course, easily analyzed in terms of consequentialistic ethics. But it is of course possible to incorporate them into a deontological ethic as well (as, for example, duties of beneficences are within Kant’s ethics). The task of those preferring to construct a hybrid model from a deontological starting point would be to find some such way of these consequential considerations within that sort of ethic. AMA 2001. World Medical Association 1948. Arvon 1997. Gurwitz, Col and Avorn 1992. Bugeja, Kumar and Banerjee 1997. Bayer and Tadd 2000. Lewis et al. 2003. See similarly Gurwitz, Col and Avorn 1992. AMA 2003, sec. E-2.071. Kipnis 2003.
Vulnerability in Research Subjects
Kenneth Kipnis University of Hawaii at Manoa The concept of "vulnerability" was basically grandfathered into the literature of research ethics, without certification. Though the Nuremberg Code emphasized the necessity of the candidate-subject’s informed consent, it ruled out essential research on children and those with cognitive impairments. In the United States, episodes like Willowbrook, the Brooklyn Jewish Chronic Disease Hospital Case, and the Tuskegee Syphilis Study, provoked the debates that eventually gave birth to our current methods for ensuring the ethical conduct of research. But despite the remarkable circumstances of the subjects involved in those three studies—institutionalized children, hospitalized elderly, and impoverished and poorly educated black Alabama males—it is not much of an exaggeration to say that, in the minds of many investigators, the paradigmatic research subject remained a mature, respectable, moderately well-educated, clear-thinking, literate, self-supporting United States citizen in good standing: i.e., a man (sic) who could understand a 12- page consent form and act intelligently on the basis of its contents. Though it is assumed here both that the existing guidelines are sufficient to deal ethically with this paradigmatic research subject and that the default protections are reliably in place, the vulnerable research subject nonetheless required an ethical consideration going beyond that baseline. The prevailing "subpopulation" approach seeks to modify these baseline standards for groups falling outside of the paradigm. The Federal Regulations on the Protection of Human Subjects (45 CFR 46) implement the requirement that institutional review boards (IRBs) take into account the "special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons." Although some of these groups have received their own "subparts" setting out special requirements, it is surely reasonable to have comparable concerns for drug abusers, the desperately ill, Ugandan women, illegal aliens, the impoverished homeless, women in the process of miscarrying, psychology undergraduates, and the elderly in the early stages of dementia. The twin tasks of confirming subpopulation vulnerability and identifying requisite protections have been plagued by conceptual murkiness. What exactly is "vulnerability" as applied to research subjects? And what should be the methods and goals in responding to it? Though commentators speak as if there were something common to these disparate groups, it has not been clear what that characteristic (or that set of characteristics) is. And even if such criteria were articulated, one would surely want to know what it was about those features that made those who possess them "vulnerable." I am here challenging the current subpopulation focus that is evident both in the writings on research ethics and in the efforts to draft subparts for groups designated as vulnerable. I am urging that the current conceptualization be supplanted by an "analytical approach," like the one to be set out here. The aim is to tease out the circumstances that directly signal the specific vulnerabilities researchers should take into account. Seven discrete types of candidate research subject (C-S) vulnerability can be distinguished, each paired with a distinct question and compensating strategies. Foreshadowing, here are the seven. Cognitive: Does the C-S have the capacity to deliberate about and decide whether to participate in the study? Situational: Does the C-S have the time and composure needed to understand and choose whether to participate in the study? Juridic: Is the C-S liable to the authority of others who may have an independent interest in that participation? Deferential: Is the C-S given to patterns of deferential behavior that may mask an underlying unwillingness to participate? Medical: Has the C-S been selected, in part, because he or she has a serious health-related condition for which there are no satisfactory treatments? Allocational: Is the C-S seriously lacking in any important social goods that will be provided as a consequence of his or her participation in research? Social: Does the C-S belong to a socially disvalued group? It is useful to return to the idea of consent, so central to the Nuremberg analysis. As with other performatives, to grant consent is to exercise an ethical power. We have the ability, merely by intoning the proper words under the right circumstances, to alter the systems of obligations and permissions that envelope us. Ordinarily it is a wrong for you to take my lawnmower. But if I say " You can take my lawnmower," an action that would have been wrong can become unexceptional. In giving permission, an act can become permitted. So the granting of consent by an informed candidate research subject (a C-S) is a precondition for ethical research. Some types of vulnerability interfere with one’s ability to give or withhold informed consent. Children, the uneducated, and persons with mental disabilities may lack the capacity to appreciate their situations and deliberate. Still others with unexpected, exigent medical conditions (women having miscarriages, for example) may lack the time and composure needed to become informed, though they are not mentally disabled. These two vulnerabilities— "cognitive" and "situational" — each represent a limit on the ability to provide informed consent. Several strategies exist to compensate for cognitive vulnerability: plain-language consent forms, advance directives (where incapacity is anticipated), supplementary educational measures, and the proper use of surrogates and subject advocates. Situational vulnerability can be addressed by community consultation and notification procedures in the context of waived consent trials for patients in emergency circumstances. However, the five other vulnerabilities are different. For even if informed consent is present, it may not suffice to affect the permissibility of research. When consent is given, something that wasn’t permitted thereby becomes permissible …usually. So if a doctor asks to examine a patient who now says "OK," this typically brings it about that the physical examination becomes OK. To consent is—characteristically but not always—to exercise a power to alter ethical relationships. Consent can change the system of obligations, permissions, and prohibitions within which we live. Though we usually think that to give informed consent is to grant permission, and to grant permission is to bring it about that some formerly prohibited act becomes permitted, informed consent in research is often insufficient to bring about permissibility. The science may be bogus; the people selected for a burdensome trial may be different from those who can benefit from the results; the risks and burdens may be excessive; there may be dangers to third parties; those conducting the study may not be up to the job; the political, organizational, economic, and social settings may not offer the integrity and resources required by the trial; and so on. While non-vulnerable participants can be wrongfully placed in harm’s way, subject vulnerability was never intended to pick out all of the areas where researchers and IRBs have to be careful. Vulnerability is only one chapter of the research ethics story. We can now examine the second route to vulnerability. Consider the following cases (Kipnis, 1992): Riley#1, unable to swim, finds himself on a raft that is sinking slowly in deep water. Mr. Hathaway, alone on the nearby shore, offers to throw a lifeline and rescue him, but only if Riley#1 agrees to pay him $10,000. Riley#1 consents and is rescued. Does Riley#1 owe Mr. Hathaway $10,000? Riley#2 finds that he has a life-threatening but curable illness. Dr. Hathaway offers to administer treatment that will cure him, but only if Riley#2 agrees to pay him $10,000. Riley#2 consents and is cured. Does Riley#2 owe Dr. Hathaway $10,000? There are at least three ways of thinking about these cases. Some—notably libertarians—treat the cases identically. Neither "rescuer" is responsible for the other’s precarious situation. Neither has a legally cognized duty to intervene. Neither makes anyone worse off. Both have offered assistance—at a price, of course—and a deal is a deal. A second group sees a powerful argument for lifeguards and universal health coverage. Just as we tax ourselves to support municipal fire fighters, those facing other life emergencies should not have to purchase vital assistance in the marketplace. An economy is ethically flawed if it treats certain vital goods as commodities. Although this approach is revealing, it dodges our question: Do the Rileys owe their debts even in flawed economies? Finally, some will scrutinize the terms of the two contracts. While it may not be unjust to have to pay $10,000 for $10,000 worth of medical care, that same sum is excessive payment for modest assistance in getting out of the water. Though both Rileys can knowingly and voluntarily enter into their respective agreements, the terms of the first contract appear to be exploitative and unconscionable, the price reflecting the fatal consequence of refusing the offer rather than the minor costs of providing the service. Both Rileys are vulnerable: precariously situated and at the mercies of their respective Hathaways. Each expects death as the consequence of rejecting the offer. But each is capable of informed consent, appreciating exactly what they must understand, and choosing reasonably enough under the circumstances. Though there is vulnerability in both cases, only Mr. Hathaway—not Dr. Hathaway— is taking unfair advantage of it. I do not think it would be exploitation if Mr. Hathaway had asked Riley#1 to pay—not $10,000—but only $10, to clean clothing he would soil in the rescue. Vulnerability makes it disturbingly easy to impose agreements that unjustly allocate benefits and burdens. These transactions must be scrutinized carefully. This second type of vulnerability does not limit informed consent. Where the candidate-subject is (1) juridically subordinated (like students, employees, soldiers, and inmates); or (2) deferential (like certain children, students, military enlistees, employees, and third-world woman); or (3) seriously lacking in opportunities or material resources (like prisoners and the Tuskegee subjects); or (4) without safe and effective medical options (like many in cancer research); or (5) socially disvalued (like prisoners, children, women, andminority groups), it is possible that the research should not be done even with informed consent, and certainly not until compensating measures are implemented. Juridic vulnerability calls attention to the formal authority relationships that often characterize social structures. The most striking examples are prisons and the military, where wardens and officers have legal authority over prisoners and enlistees. But the category also includes children under the authority of their parents, psychology students subordinated to their college professors, institutionalized persons (including institutionalized children and their parents) subject to the authority of custodians, and certain third-world woman who may be legally subject to their husbands. Related issues can arise when the candidate-subjects are engaged in illicit activities. This catalogue is not exhaustive. In these cases researchers must ask: "Is the C-S liable to the authority of others who may have an independent interest in that participation?" The worry is that the "consent" of the CS might be merely a reflection of the wishes of those in authority. This distinctive vulnerability—the juridic fact of their subordination to the authority of another—can call into question the validity of their consent. This is especially a concern when those in authority are also those who are conducting, commissioning, or somehow benefiting from the research. In its Final Report on human research in the military, the Advisor y Committee on Human Radiation Experiments (ACHRE) recommended that officers be specifically excluded from recruitment sessions and that an ombudsman be present to insure that the voluntariness of participation is adequately stressed. Likewise, children can be questioned separately from their parents and confidentially. The task for the researcher is to devise a consent procedure that will adequately insulate the C-S from the hierarchical system to which he or she is subject. While juridic subordination directs our attention to objective features of the formal hierarchical context within which the C-S functions, deferential vulnerabilities are, instead, subjective responses to certain others. To be sure, the two are often present together. With respect to officers, enlistees are generally both deferential and juridically subordinated. But when, in the presence of intimates and friends, one is exhorted to stand up on behalf of a popular cause, one may care deeply about the opinions of those others even though they do not occupy formal positions of authority. Researchers need to understand these powerful social and cultural pressures and devise consent procedures that take them into account. Those involved in subject accrual need to be selected with care, perhaps with the advice of local informants or consultants in psychology and anthropology. The conversational setting may require attention. The challenge is to devise a process that eliminates as much as possible the social pressures that a candidate-subject may feel even if, in reality, they are not being imposed. Medically vulnerable candidate-subjects are those who are under consideration because of serious health-related conditions for which there are no satisfactor y remedies. Metastatic cancers can fall into this category, as can severe spinal cord injuries, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, end-stage AIDS, and so on. Also included are illnesses for which there are treatments that are not suitable for particular patients. Rescue therapy for cancer, requiring transfusions, is not a suitable treatment for most Jehovah’s Witnesses. What makes these patients vulnerable is their medically exigent state. Having run out of options, they will be willing— even eager—to undergo risks that would ordinarily be foolish. The classic problem with research on medically vulnerable patients is an apparently ineliminable "therapeutic misconception" affecting the majority of these subjects. The patients know there are no satisfactory standard treatments and that, based on pre-clinical research, scientists are testing a drug that might be safe and effective. Despite warnings to the contrary, many of these subjects are eager to enter trials on the chance they will benefit from access to a drug that works. But Phase 1 clinical trials are not supposed to be about efficacy: They are primarily designed to assess safety. The research subject is vulnerable—so the story goes—because he or she is driven by a false but persistent hope for a cure and, accordingly, is likely to enter the study out of an unreasonable expectation of success. But even if the unproven drug is, in reality, both safe and effective, it is often unlikely that a medically exigent research subject can benefit from it. Since the primary purpose is to assess safety, patients may receive theoretically sub-therapeutic dosages. But instead of receiving increased dosages when tumors progress without adverse reactions, patients are typically removed from the study and denied possible benefits. And even if efficacy appears, the trial can end, leaving improving patients in the lurch. A fairer division of benefits and burdens would require that trials be designed to assure patients that they WILL have a chance of benefitting from participation IF it turns out that the drug is safe and effective. To fail to do so is to take unfair advantage of these research subjects’ vulnerability. One way to do this would be to guarantee to subjects that there are only five ways in which they will come off the study. Either (#1) they choose to leave the study; or (#2) they seriously fail to comply with the protocol and are removed; or (#3) significant adverse reactions are seen in response to the drug and the trial ends; or (#4) they die; or (#5) they are stabilized or cured. While candidate-subjects should be assured that #5 is unlikely, the study design takes seriously the medically exigent patient’s overriding interest in maximizing the possibility of therapeutic benefit. It is a less exploitative arrangement. Under this "maximum therapeutic benefit" standard, the primary concern would still be the scientific validity of the research design. But, having satisfied that requirement, the patient’s powerful interest in improvement would have to appear prominently on the researcher’s radar screen. If the internal benefit of research is a safe and effective therapy, the external benefits are the various other compensations that research subjects receive. But a C-S in a state of allocational vulnerability is seriously lacking in other socially distributed goods: money, housing, medical care, childcare, burial benefits, opportunities to benefit the community, and so on. The question for the investigator is: "Is the C-S seriously lacking in important social goods that will be provided as a consequence of his or her participation in research?" (On occasion, it may also be pertinent to ask whether the C-S is seriously burdened with social evils that will be relieved as a consequence of participation. This issue is especially pertinent for research on prisoners. Now if Job-Seeker is destitute and hungry, and Business-Owner offers him a good job at a decent wage, and Job-Seeker accepts (notwithstanding that it is the only acceptable option), we would not concern ourselves with the voluntariness of the acceptance so long as the terms of employment were fair. But if Business-Owner offers sub-subsistence compensation, and the work is dangerous, and there are no workers’ compensation benefits, communities are likely to invalidate the agreement. We will do this, not because Job-Seeker had no other choice, but because the bargain was unconscionably exploitative. As with medical exigency, the vulnerability is to be found in Job-Seeker’s precarious position: economic in this instance. But this allocational disadvantage should direct our attention to the substance of the bargain: Is it fair to the party in the weaker position? The minimum wage, job safety regulations, and workers’ compensation benefits are all broadly-supported means of reducing such exploitation. In biomedical research, the vulnerabilities associated with allocational disadvantage arise in many ways. The researcher needs to ask whether the deprivation has led to acceptance of an exploitative offer. While allocations are often the result of impersonal socio-economic forces, the basis for ethical concern is compounded when someone with juridic authority over the C-S is distributing the goods in question. Prisons and the military, for example, may function in this way. It is difficult to distinguish between just and unjust compensation packages. Of the seven types of vulnerability, allocational disadvantage is probably the most problematic. We often assume that if a bargain is satisfactor y to both parties, others should not interfere. But participation as a subject in medical research can impose risks and burdens that properly attract community attention. While we do not want to see people treated unfairly, we are not very confident applying the concept of the just price. I suggest we consider the standards that we routinely apply to other comparable remunerative activities. Although the point has been urged before, it is hard to grasp why research subjects should not normally be entitled to medical treatment for the injuries they suffer; why they should be asked to subsidize the research enterprise in that unusually burdensome way. Surely if we extended broad community standards into this aspect of research, we would begin by securing a right to some version of "workers’ compensation." Social vulnerability points to the ways in which entrenched prejudice and streotypical thinking can compromise the care and consideration that would ordinarily be present. The question for researchers is "Does the C-S belong to a socially undervalued group?" The worry is that stigmatizing perceptions will adversely affect the process of developing, implementing, and reviewing the protocol. Although more needs to be said about the appropriate responses to this type of vulnerability, the involvement of members of these socially disvalued groups in the review and implementation process could provide some needed protection, along with corrective education as needed. Projects that needlessly single out the members of such groups for study might well require added scrutiny during the review process. Finally, the sensitive understanding of vulnerability—the many precariousnesses that afflict the human condition— exposes a certain universality in these themes even while grounding a broader case for kindness and sensitivity. None of us is without some cognitive limitation. Everyone is subject to juridic authority, not all of which is wisely benevolent. Socialization itself entails patterns of deference. All of us face an eventual and too real prospect of medical exigency. And no one is immune from extreme and exigent need and the harms that can flow from prejudice and other deficits in the systems we count on to provide us with essential services and protections. Nor are researchers the only ones who need to learn how to engage the vulnerable with sensitivity and honor. The topic surely has an importance extending beyond the boundaries of research ethics. References An early version of this paper was commissioned by the National Bioethics Advisor y Commission and is available at: http:// onlineethics.org/reseth/nbac/hkipnis.html Kipnis, K. Vulnerability in Research Subjects: A Bioethical Taxonomy. In National Bioethics Advisory Commission. Ethical and policy issues in research involving human research participants. Bethesda, MD, 2001. G1–G13. The materials on coercive offers were adapted from Kipnis, K. "Bargaining" in Lawrence C. Becker, ed., The Encyclopedia of Ethics. Garland Publishing, 1992.
Reflections on Kipnis’s Concept of Medical Vulnerability
Dorothy E. Vawter and Karen G. Gervais Minnesota Center for Health Care Ethics Kipnis makes several significant contributions to understanding and responding to various types of vulnerability in research participants. Most importantly, he replaces the federal regulations’ "subpopulation" approach to identifying and responding to vulnerability with an "analytic" approach. Distinguishing seven types of participant vulnerability, namely, cognitive, situational, juridic, deferential, medical, allocational, and social vulnerability, he recommends a special protection for each (Kipnis 2001; Kipnis 2004a). His analysis of medical vulnerability and its remedy is provocative and problematic. We consider the adequacy of Kipnis’s assessment of the source and scope of medical vulnerability and his recommended special protection for medically vulnerable participants. Moreover, we weigh whether his proposal to maximize therapeutic benefit is more appropriately incorporated in modified regulations for the protection of vulnerable research participants or is best viewed as an aspirational guideline for researchers and IRBs.
Background Human research participants routinely are assured several core protections. For example, IRBs engage in prior interdisciplinary review of the study protocol, the consent process and consent form, and they assess whether the risks that have been minimized are consistent with sound research design and whether the risks are reasonable in light of the benefits. Researchers and IRBs often go beyond the core protections and provide one or more special protections as well. More rigorous recruitment and consent procedures are two of the most common types of special protections (see examples in list below). Without being exhaustive, the following list shows the range of special protections that can be used to mitigate vulnerability. Assign recruitment responsibilities to someone independent of the study Support the consent process with additional educational activities, use consent advocates or surrogates, strengthen disclaimers in the consent process and materials, formally assess competence and comprehension Require additional levels, frequency, and types of review of the study and its conduct Increase representation by those who are to participate in the research in the design and/or review of the study Minimize risk through the conduct of more preclinical studies, use of clear stopping rules and data safety monitoring boards (DSMBs), and compensation of participants in the event they are harmed Increase benefits by insisting on the prospect of therapeutic benefit, and direct adequate attention to the merits of the study question and design Cap the level of risk for research involving children, per regulation Depending on the study design, the vulnerability of the participants, and the investigational interventions, among other factors, any number of these special protections may be appropriate.
Kipnis on Special Protection for Medically Vulnerable Participants Prospective research participants are medically vulnerable, Kipnis maintains, when they have serious health-related conditions for which there are no satisfactory treatments, putting them at increased risk of being exploited for research purposes. What makes them vulnerable is "having run out of options, they will be willing—even eager—to undergo risks that would ordinarily be foolish." An "ineliminable ‘therapeutic misconception’" drives their "false but persistent hope for a cure," and they are "likely to enter (studies) out of an unreasonable expectation of success" (Kipnis 2001, 2004a). Kipnis maintains that participants need to be protected from researchers’ inattention to medical vulnerability and "agreements that unjustly allocate benefits and burdens" (Kipnis 2004a). He urges researchers and IRBs to be more responsive to participants’ "overriding interest" in a chance at therapy. Particularly provocative is Kipnis’s suggestion that IRBs and researchers attend to the arrangement of benefits and burdens between a researcher and her study participants— "to the substance of the bargain." This introduces a set of considerations different from those that IRBs customarily attend to. In Kipnis’ view, researchers and IRBs should be more vigilant and purposeful in their efforts to protect prospective participants from exploitation. It is the unfair taking advantage of participants deprived of therapeutic options that Kipnis believes needs to be remedied. Special recruitment and consent protections are insufficient in Kipnis’s view. The risk of the therapeutic misconception by medically vulnerable participants is so high, serious, and inevitable, that it is futile to expend effort to mitigate it. He advocates, instead, a sole special protection for medically vulnerable participants—namely, maximizing therapeutic benefit—not only within a study, but possibly long-term after the completion of a study. He asks, "given the interests and aspirations of both parties (and the poor bargaining position of one), is there a fair division of the benefits and burdens of cooperation?" (Kipnis 2001) His objective is to make the cooperative relationship between researcher and participant as well as the arrangement of benefits and burdens between them, fairer, kinder, and more sensitive. (Kipnis 2001, 2004a).
Critique Kipnis’s proposal exceeds the bounds of common IRB practices and the regulatory requirements that the risks of a study be minimized and be reasonable in light of any expected benefits. But how should we understand his recommendations? Is he, for instance, offering a new regulatory standard for protecting medically vulnerable participants? We believe Kipnis’s recommendation is best understood as aspirational, rather than a minimum requirement of the sort that comprise regulations. He acknowledges that promising therapeutic benefit after the completion of a study does not transform a study in which the risks are unreasonable, into a study in which they are reasonable (Kipnis 2004b). But it can enhance the fairness of the relationship between researcher and participant. It has the potential to make the "arrangement" of interests fairer and less prone to exploitation. Considering and adjusting the arrangement of interests between the researcher and study participants is an activity different from adjusting the arrangement of risks and benefits within a study. Kipnis’ recommendation to maximize therapeutic benefit is more a type of inducement or compensation than a protection. It is well recognized that efforts to sweeten invitations to clinical research raise the prospect of unduly inducing people to participate. Kipnis does nothing to reassure us that his open-ended call for maximizing therapeutic benefit avoids problems of undue inducement and protects against the therapeutic misconception and exploitation. Requiring or even allowing offers of therapeutic benefit at the end of a study, depending on the study, may be counterproductive (Dresser 2002). When there is little prospect that a therapeutic benefit will become available after a study, promises of possible future benefit may encourage medically vulnerable persons to agree to participate in studies they would not otherwise agree to. Such promises can easily exacerbate rather than mitigate the therapeutic misconception. If the prospective participant inferred "I might get better " when told "You will undergo these risks, but therapeutic benefit is unlikely and not to be expected," surely she will infer, "I will benefit" when promised; "If there is benefit later, you will receive it." Recommending that investigators promise participants a potentially therapeutic study intervention either within studies or after the studies have been completed, is reasonable in some cases (Freeman 1999). Kipnis’s error lies in generalizing from his reflections on one particular study (a phase I dose escalation study of an angiogenesis inhibitor—which boasts an unusually low toxicity—in cancer patients lacking other options) to all studies involving medically vulnerable participants (Kipnis 2001, 2004a). Kipnis himself lists a wide range of circumstances in which people may be medically vulnerable: metastatic cancer, severe spinal cord injuires, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, end-stage AIDS, and rescue transfusions for Jehovah’s Witnesses. His examples of an angiogenesis inhibitor in cancer patients and transfusions in Jehovah’s Witnesses provide important clues that issues of vulnerability and special protection involve attention to multiple considerations, including characteristics of the particular disease, the particular intervention(s) being studied, and the study design. The diversity of medically vulnerable people and types of studies involving them suggest the implausibility of just a single special protection for this category of vulnerability. Moreover, we disagree that efforts to mitigate the therapeutic misconception are futile. Instead we join Appelbaum and Dresser, among others, who maintain that there are ways to avoid and minimize the force of the therapeutic misconception (Appelbaum 1987; Dresser 2002). In our view, therefore, Kipnis is unwise to reject and abandon special protections directed at recruitment and consent for medically vulnerable participants. It is important to embrace these and many other special protections depending on the particulars of a given study. Kipnis’s proposal to maximize benefits is problematic for practical reasons as well. It is so stringent a standard that it makes many otherwise acceptable studies infeasible; it needs qualification. Requiring that the therapeutic benefits be maximized—without further qualification—may have the unintended effect of raising the bar on what research can and will be conducted. It may make the conduct of some research prohibitively expensive and so burdensome for sponsors, researchers, and funders that it will not be conducted. From where shall researchers find the funds to cover the costs of long-term continued use of investigational interventions after a study is complete? Might the obligations differ depending on whether the researcher is an individual clinician or a manufacturer? What sorts of competing interests of the researcher, in Kipnis’s view, might be compelling enough to limit the obligation to maximize therapeutic benefit for participants in her studies? Moreover, researchers may not be permitted to promise an unapproved FDA-regulated product off-study without prior approval from the FDA—an approval that may be difficult to obtain so far in advance. Alternatively, if Kipnis is calling for radical changes in the institutions and infrastructures surrounding and supporting clinical research, he needs to offer more detail and justification for such radical recommendations. Finally, un