This book provides an analysis of the debate surrounding cultural diversity, and attempts to reconcile the seemingly opposing views of "ethical imperialism," the belief that each individual is entitled to fundamental human rights, and cultural relativism, the belief that ethics must be relative to particular cultures and societies. The author examines the role of cultural tradition, often used as a defense against critical ethical judgments. Key issues in health and medicine are explored in the context of cultural diversity: the physician-patient (...) relationship, disclosing a diagnosis of a fatal illness, informed consent, brain death and organ transplantation, rituals surrounding birth and death, female genital mutilation, sex selection of offspring, fertility regulation, and biomedical research involving human subjects. Among the conclusions the author reaches are that ethical universals exist, but must not be confused with ethical absolutes. The existence of ethical universals is compatible with a variety of culturally relative interpretations, and some rights related to medicine and health care should be considered human rights. Illustrative examples are drawn from the author's experiences serving on international ethical review committees and her travels to countries in Africa, Asia, and Latin America, where she conducted educational workshops and carried out out her own research. (shrink)

The aim of this article is twofold. First, it is argued that while the principle of ‘ought implies can’ is certainly plausible in some form, it is tempting to misconstrue it, and that this has happened in the way it has been taken up in some of the current literature. Second, Kant's understanding of the principle is considered. Here it is argued that these problematic conceptions put the principle to work in a way that Kant does not, so that there (...) is an important divergence here which can easily be overlooked. (shrink)

Despite broad agreement that the vulnerable have a claim to special protection, defining vulnerable persons or populations has proved more difficult than we would like. This is a theoretical as well as a practical problem, as it hinders both convincing justifications for this claim and the practical application of required protections. In this paper, I review consent-based, harm-based, and comprehensive definitions of vulnerability in healthcare and research with human subjects. Although current definitions are subject to critique, their underlying assumptions may (...) be complementary. I propose that we should define vulnerability in research and healthcare as an identifiably increased likelihood of incurring additional or greater wrong. In order to identify the vulnerable, as well as the type of protection that they need, this definition requires that we start from the sorts of wrongs likely to occur and from identifiable increments in the likelihood, or to the likely degree, that these wrongs will occur. It is limited but appropriately so, as it only applies to special protection, not to any protection to which we have a valid claim. Using this definition would clarify that the normative force of claims for special protection does not rest with vulnerability itself, but with pre-existing claims when these are more likely to be denied. Such a clarification could help those who carry responsibility for the protection of vulnerable populations, such as Institutional Review Boards, to define the sort of protection required in a more targeted and effective manner. (shrink)

The leading ethical position on placebo-controlled clinical trials is that whenever proven effective treatment exists for a given condition, it is unethical to test a new treatment for that condition against placebo. Invoking the principle of clinical equipoise, opponents of placebo-controlled trials in the face of proven effective treatment argue that they (1) violate the therapeutic obligation of physicians to offer optimal medical care and (2) lack both scientific and clinical merit. We contend that both of these arguments are mistaken. (...) Clinical equipoise provides erroneous ethical guidance in the case of placebo-controlled trials, because it ignores the ethically relevant distinction between clinical trials and treatment in the context of clinical medicine and the methodological limitations of active-controlled trials. Placebo controls are ethically justifiable when they are supported by sound methodological considerations and their use does not expose research participants to excessive risks of harm. (shrink)

This paper critically examines a particular strategy for resolving the central ethical dilemma associated with randomized clinical trials — the “community equipoise” strategy . The dilemma is that RCTs appear to violate a physician's duty to choose that therapy which there is most reason to believe is in the patient's best interest, randomizing patients even once evidence begins to favor one treatment. The community equipoise strategy involves the suggestion that our judgment that neither treatment is to be preferred is to (...) be assessed according to a community rather than an individual standard. Thus, though a physician may personally believe that there is some reason to prefer one treatment, patients can legitimately be randomized if there remains disagreement in the community of medical professionals. Rationales in favor of this conception include the following: medical knowledge is best understood as residing in the community, the judgments of others count as evidence, and so should change one's own opinion, subjects would not be better off outside the trial, and the point of any trial is the resolution of dispute in the medical community. I critically examine these rationales and argue that they are insufficient. Amongst the problems are tensions between various of these underlying rationales, and important ambiguities in just what the CE criterion is to amount to. Finally, I argue that even if use of CE was justified, it would not justify carrying out RCTs anywhere near long enough to discharge our duty to gain reliable knowledge on which to base safe and effective medical practice. Hence, we need some different justification for carrying out RCTs. (shrink)

: When may a physician legitimately offer enrollment in a randomized clinical trial (RCT) to her patient? Two answers to this question have had a profound impact on the research ethics literature. Equipoise, as originated by Charles Fried, which we term Fried's equipoise (FE), stipulates that a physician may offer trial enrollment to her patient only when the physician is genuinely uncertain as to the preferred treatment. Clinical equipoise (CE), originated by Benjamin Freedman, requires that there exist a state of (...) honest, professional disagreement in the community of expert practitioners as to the preferred treatment. FE and CE are widely understood as competing concepts. We argue that FE and CE offer separable and, in themselves, incomplete justifications for the conduct of clinical trials. FE articulates conditions under which the fiduciary duties of physician to patient may be upheld in the conduct of research. CE sets out a standard for the social approval of research by institutional review boards. Viewed in this way, FE and CE are not necessarily competing notions, but rather address complementary moral concerns. (shrink)

: The debate over when medical research may be performed in developing countries has steered clear of the broad issues of social justice in favor of what seem more tractable, practical issues. A better approach will reframe the question of justice in international research in a way that makes explicit the links between medical research, the social determinants of health, and global justice.

Book reviewed in this article: Principles of Biomedical Ethics. By Tom L. Beauchamp and James F. Childress.

This paper critically examines a particular strategy for resolving the central ethical dilemma associated with randomized clinical trials (RCTs) — the “community equipoise” strategy (CE). The dilemma is that RCTs appear to violate a physician's duty to choose that therapy which there is most reason to believe is in the patient's best interest, randomizing patients even once evidence begins to favor one treatment. The community equipoise strategy involves the suggestion that our judgment that neither treatment is to be preferred (that (...) there obtains a state of “equipoise”) is to be assessed according to a community rather than an individual standard. Thus, though a physician may personally believe that there is some reason to prefer one treatment, patients can legitimately be randomized if there remains disagreement in the community of medical professionals. Rationales in favor of this conception include the following: (i) medical knowledge is best understood as residing in the community, (ii) the judgments of others count as evidence, and so should change one's own opinion, (iii) subjects would not be better off outside the trial, and (iv) the point of any trial is the resolution of dispute in the medical community. I critically examine these rationales and argue that they are insufficient. Amongst the problems are tensions between various of these underlying rationales, and important ambiguities in just what the CE criterion is to amount to. Finally, I argue that even if use of CE was justified, it would not justify carrying out RCTs anywhere near long enough to discharge our duty to gain reliable knowledge on which to base safe and effective medical practice. Hence, we need some different justification for carrying out RCTs. (shrink)

Researchers do not owe their subjects the same level of care that physicians owe patients, but they owe more than merely what the research protocol stipulates. In keeping with the dynamics of the relationship between researcher and subject, they have limited but substantive fiduciary obligations.

A predominant ethical view holds that physician‐investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second‐rate treatments, the experimental intervention and the best proven therapy should appear equally effective. "Clinical equipoise" is necessary. But this perspective is flawed. The ethics of research and of therapy are fundamentally different, and clinical equipoise should be abandoned.

Physician‐investigators face the daunting task of enrolling desperate patients into Phase I cancer trials that are not meant to be therapeutic. Patients doggedly regard the trials as therapeutic, and researchers tend to collaborate in their confusion by glossing the trials’ true purposes and noting the occasional benefit that subjects accidentally receive. The disparity between hope and fact must be redressed by degrees, from many angles at once.

No consensus yet exists on how to handle incidental fnd-ings in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are fndings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers (...) have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed. (shrink)

Concerns about exploiting the poor or economically disadvantaged in clinical research are widespread in the bioethics community. For some, any research that involves economically disadvantaged individuals is de facto ethically problematic. The economically disadvantaged are thought of as “venerable” to exploitation, impaired decision making, or both, thus requiring either special protections or complete exclusion from research. A closer examination of the worries about vulnerabilities among the economically disadvantaged reveals that some of these worries are empirically or logically untenable, while others (...) can be better resolved by improved study designs than by blanket exclusion of poorer individuals from research participation. The scientific objective to generate generalisable results and the ethical objective to fairly distribute both the risks and benefits of research oblige researchers not to unnecessarily bar economically disadvantaged subjects from clinical research participation. (shrink)

Scientific research and ethics -- Ethical theory and decision making -- Data acquisition and management -- Mentoring and professional relationship -- Collaboration in research -- Authorship -- Publication and peer review -- Misconduct in research -- Intellectual property -- Conflicts of interest and scientific objectivity -- The use of animals in research -- The use of human subjects in research -- The use of vulnerable subjects in research -- Genetics, cloning, and stem cell research -- International research.

In this book, Dr. Robert J. Levine reviews federal regulations, ethical analysis, and case studies in an attempt to answer these questions.

This paper discusses a dispute concerning the ethics of research on preventing the perinatal transmission of HIV in developing nations. Critics of this research argue that it is unethical because it denies a proven treatment to placebo‐control groups. Since studies conducted in developed nations would not deny this treatment to subjects, the critics maintain that these experiments manifest a double standard for ethical research and that a single standard of ethics should apply to all research on human subjects. Proponents of (...) the research, however, argue that these charges fail to understand the ethical complexities of research in developing nations, and that study designs can vary according to the social, economic, and scientific conditions of research. This essay explores some of the ethical issues raised by this controversial case in order to shed some light on the deeper, meta‐ethical questions. The paper argues that standards of ethical research on human subjects are universal but not absolute: there are some general ethical principles that apply to all cases of human subjects research but the application of these principles must take into account factors inherent in particular situations. (shrink)

Some authors argue that the ethics of medical care and the ethics of research differ, and that it is a mistake to conflate the two. They propose “that medical research and medical treatment are two distinct forms of activities, governed by different ethical principles.” This raises the question of whether physicians who are also clinical investigators may separate their role as physician from that of researcher when they are involved in clinical trials, thereby avoiding the obligations required in the physician-patient (...) relationship. Miller and Brody suggest that medical training is to blame for what they believe is the physicians’ tendency to confound the obligations of research and practice. “Physician-investigators, after all, went to medical school” they explain. They believe that considering research with patients outside the ethical framework of the physician-patient relationship may be “difficult and threatening” to physicians who have “psychological needs” to consider the ethical obligations flowing from their relationship with their patients. (shrink)

One of the most important questions in the ethics of human clinical research asks what obligations investigators owe the people who enroll in their studies. Research differs in many ways from standard care - the added uncertainties, for instance, and the nontherapeutic interventions such as diagnostic tests whose only purpose is to measure the effects of the research intervention. Hence arises the question whether a physician engaged in clinical research has the same obligations toward research subjects that he owes his (...) medical patients, or whether they differ in any fundamental way.Perhaps the most common answer is that the relationship is the same. Investigators, like physicians, are said to be fiduciaries of the volunteers who enroll in research trials. Each owes the best available medical care, which means that a physician can only justify enrolling his patient in research if the study meets the requirements of clinical equipoise, namely, that there is legitimate disagreement within the medical community as to whether the standard treatment or the investigational intervention is superior. (shrink)

Medical research is widely thought to have a fundamentally therapeutic orientation, in spite of the fact that clinical research is thought to be ethically distinct from medical care. We need an entirely new conception of clinical research ethics—one that looks to science instead of the doctor‐patient relationship.

If people sometimes participate in research because of altruism—because they want to help in the search for treatments—should we revise our views about what kinds of experiments are ethical? If participants act out of altruism, we might let them accept greater risks than we would if they are motivated only by a desire for personal gain. But how can we know when participants are genuinely altruistic?

When environmental health researchers study hazards in the home, they often discover information that may be relevant to protecting the health and safety of the research subjects and occupants. This article describes the ethical and legal basis for a duty to warn research subjects and occupants about hazards in the home and explores the extent of this duty. Investigators should inform research subjects and occupants about the results of tests conducted as part of the research protocol only if the information (...) is likely to be accurate, reliable, and medically useful. Investigators should warn subjects and occupants about hazards they happen to discover while they are in the home, if a reasonable person would warn the subjects and occupants about those hazards. Investigators should not report illegal hazards discovered in the home to the authorities, unless those hazards constitute abuse or neglect of children or mentally disabled people living in the home. When investigators decide to warn research subjects and occupants about hazards in the home, they should take some steps to help them make effective use of this information, such as providing additional counselling or making a referral for remediation or medical treatment. Investigators should discuss these issues with research subjects during the informed consent process. (shrink)

This essay analyzesexploitation in biomedical research in terms ofthree basic elements: harm, disrespect, orinjustice. There are also degrees ofexploitation, ranging from highly exploitationto minimally exploitation. Althoughexploitation is prima facie wrongful,some exploitative research studies are morallyjustified, all things considered. The reasonan exploitative study can still be ethical isthat other moral considerations, such as theautonomy of the research subject or the socialbenefits of research, may sometimes justifystudies that are minimally exploitative. Calling a research project exploitative doesnot end the debate about the merits (...) of thestudy but invites one to ask additionalquestions about how the study is exploitative,and whether the study is justifiablenevertheless. (shrink)

In the research ethics literature, there is strong disagreement about the ethical acceptability of placebo-controlled trials, particularly when a tested therapy aims to alleviate a condition for which standard treatment exists. Recently, this disagreement has given rise to debate over the moral appropriateness of the principle of clinical equipoise for medical research. Underlying these debates are two fundamentally different visions of the moral obligations that investigators owe their subjects.Some commentators and ethics documents claim that physicians, whether acting as care givers (...) or researchers, have the same duty of beneficence towards their patients and subjects: namely, that they must provide optimal medical care. In discussing placebo surgery in research on refractory Parkinson's disease, Peter Clark succinctly states this view: “The researcher has an ethical responsibility to act in the best interest of subjects.”. (shrink)

Exploitation locates what it is we recognize as bad when we judge a situation to be exploitative. Ideal for courses in social and political philosophy, public policy, or political science.

The need for continuing provision of beneficial experimental interventions after research is concluded remains a controversial topic in bioethics for research. Based on the principle of beneficence, justice as reciprocity, concerns about exploitation and fair benefits, participants should be able to have continuing access to benefits beyond the research period. However, there is no consensus about whether or not post-trial provision of beneficial interventions should be mandatory for participants from developing countries. This paper summarises recommendations from international and national guidelines. (...) Ethical principles and practical issues relating to post-trial provision are also discussed. In conclusion, post-trial provision is not necessary in all situations and a set of criteria are proposed to identify the situations that beneficial interventions should be provided beyond the research period. However, mandatory post-trial supply of beneficial experimental interventions should be assured for those who still need and are able to benefit from them but have no alternative access. Mandatory provision is based on universal bioethical principles such as beneficence and justice. Furthermore, difficulties associated with implementation of post-trial provision are not unmanageable. Careful advanced planning and a comprehensive partnership among relevant parties would be very helpful in solving these difficulties in practice, which therefore should not be taken as an excuse to escape post-trial responsibility. (shrink)

It is universally accepted that informed consent to participate in medical research should be given by subjects. People have the fundamental human right to freely choose, without coercion or withholding of information necessary to make a reasonable choice, whether they will undergo any risks associated with a research project. United States researchers have known for some time that they have the duty to inform potential subjects of the nature of proposed research and the risks and possible benefits, and to seek (...) consent. Investigators also have the duty to design the research so that it will be scientifically valid while minimizing foreseeable and avoidable harms. (shrink)

Bioethics is currently witnessing unprecedented debate over the moral and legal norms governing the conduct of clinical research. At the center of this debate is the duty of care in clinical research, and its most widely accepted specification, clinical equipoise. In recent work, we have argued that equipoise and cognate concepts central to the ethics of clinical research have been left unnecessarily vulnerable to criticism. We have suggested that the vulnerability lies in the conspicuous absence of an articulated foundation in (...) moral and legal theory of the physician-researcher's duty of care to the patient-subject. We have repeatedly suggested that the requisite foundation is in the ethics of trust and the law of fiduciaries.Curiously, despite the absence of a published thorough exposition of our position, some have preemptively criticized our suggestion that the relationship between physician-researcher and patient-subject is fiduciary. Others have offered their own accounts of the implications of fiduciary law for the relationship. (shrink)

Franklin G. Miller and colleagues have stimulated renewed interest in research ethics through their work criticizing clinical equipoise. Over three years and some twenty articles, they have also worked to articulate a positive alternative view on norms governing the conduct of clinical research. Shared presuppositions underlie the positive and critical dimensions of Miller and colleagues' work. However, recognizing that constructive contributions to the field ought to enjoy priority, we presently scrutinize the constructive dimension of their work. We argue that it (...) is wanting in several respects. (shrink)

This paper examines the role of equipoise in evaluating international research. It distinguishes two possible formulations of the equipoise requirement that license very different evaluations of international research proposals. The interpretation that adopts a narrow criterion of similarity between clinical contexts has played an important role in one recent controversy, but it suffers from a number of problems. An alternative interpretation that adopts a broader criterion of similarity does a better job of avoiding both exploitation of the brute fact of (...) social deprivation and the exploitation of needy populations for the benefit of more well-off populations. It also holds out the promise of reconciling the need to find interventions that can be employed in developing world contexts with the cluster of moral values that must constrain the way such research is carried out. (shrink)

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by (...) healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. *Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government. (shrink)

Heated debate surrounds the question whether the relationship between physician-researcher and patient-subject is governed by a duty of care. Miller and Weijer argue that fiduciary law provides a strong legal foundation for this duty, and for articulating the terms of the relationship between physician-researcher and patient-subject.

In the research ethics literature, there is strong disagreement about the ethical acceptability of placebo-controlled trials, particularly when a tested therapy aims to alleviate a condition for which standard treatment exists. Recently, this disagreement has given rise to debate over the moral appropriateness of the principle of clinical equipoise for medical research. Underlying these debates are two fundamentally different visions of the moral obligations that investigators owe their subjects.Some commentators and ethics documents claim that physicians, whether acting as care givers (...) or researchers, have the same duty of beneficence towards their patients and subjects: namely, that they must provide optimal medical care. In discussing placebo surgery in research on refractory Parkinson's disease, Peter Clark succinctly states this view: “The researcher has an ethical responsibility to act in the best interest of subjects.”. (shrink)

: Medical research is widely thought to have a fundamentally therapeutic orientation, in spite of the fact that clinical research is thought to be ethically distinct from medical care. We need an entirely new conception of clinical research ethics—one that looks to science instead of the doctor-patient relationship.

Clinical research employing the randomized clinical trial has, traditionally, been understood to pose an ethical dilemma. On the one hand, each patient ought to get the treatment that best meets her needs, as judged by the patient in consultation with her doctor. On the other hand, the method most helpful to advancing our understanding about what treatments are indeed best able to meet patient needs is the randomized trial, which necessitates that each patient's care is decided not by physician judgment (...) or patient choice but instead by random assignment. The tension can be described as a conflict between the interests of individual patients who are sick today, and the interests of the group of people who will become sick in the future and would benefit from advances in medical understanding. How one ought to balance these important and often competing interests is an important ethical question that resists easy resolution. (shrink)

The best way to distinguish treatment from research is by their functions. This mode of distinction fits well with the basic ethical work that needs to be carried out. The distinction needs to serve as an ethical flag, highlighting areas in which the goals of doctors and patients are more likely than usual to diverge. The distinction also allows us to illuminate and understand some otherwise puzzling elements of debates on research ethics: it shows the peculiarity of exclusive conceptions of (...) the distinction between research and treatment; it allows us to frame questions about therapeutic obligations in the research context, and it allows us to consider whether there may be research obligations in the therapeutic context. (shrink)

The equipoise requirement in clinical research demands that, if patients are to be randomly assigned to one of two interventions in a clinical trial, there must be genuine doubt about which is better. This reflects the traditional view that physicians must never knowingly compromise the care of their patients, even for the sake of future patients. Equipoise has proven to be deeply problematic, especially in the Third World. Some recent critics have argued against equipoise on the grounds that clinical research (...) is fundamentally distinct from clinical care, and thus should be governed by different norms. I argue against this "difference position," and instead take issue with the traditional, exclusively patient-centered account of physicians' obligations that equipoise presupposes. In place of this traditional view, I propose a Kantian test for the reasonable partiality that physicians should show their patients, focusing on its application in clinical research and medical education. (shrink)

The practice of paying research subjects for participating inclinical trials has yet to receive an adequate moral analysis.Dickert and Grady argue for a wage payment model in whichresearch subjects are paid an hourly wage based on that ofunskilled laborers. If we accept this approach, what follows?Norms for just working conditions emerge from workplacelegislation and political theory. All workers, includingpaid research subjects under Dickert and Grady''s analysis,have a right to at least minimum wage, a standard work week,extra pay for overtime hours, (...) a safe workplace, no faultcompensation for work-related injury, and union organization.If we accept that paid research subjects are wage earners likeany other, then the implications for changes to current practiceare substantial. (shrink)

Federal policies on human subjects research have undergone a progressive transformation. In the early decades of the twentieth century, federal policies largely relied on the discretion of investigators to decide when and how to conduct research. This approach gradually gave way to policies that augmented investigator discretion with externally imposed protections. We may now be entering an era of even more stringent external protections. Whether the new policies effectively absolve investigators of personal responsibility for conducting ethical research, and whether it (...) is wise to do so, remains to be seen. (shrink)

Some authors argue that the ethics of medical care and the ethics of research differ, and that it is a mistake to conflate the two. They propose “that medical research and medical treatment are two distinct forms of activities, governed by different ethical principles.” This raises the question of whether physicians who are also clinical investigators may separate their role as physician from that of researcher when they are involved in clinical trials, thereby avoiding the obligations required in the physician-patient (...) relationship. Miller and Brody suggest that medical training is to blame for what they believe is the physicians’ tendency to confound the obligations of research and practice. “Physician-investigators, after all, went to medical school” they explain. They believe that considering research with patients outside the ethical framework of the physician-patient relationship may be “difficult and threatening” to physicians who have “psychological needs” to consider the ethical obligations flowing from their relationship with their patients. (shrink)

The doctrine of clinical equipoise is appealing because it appears to permit physicians to maintain their therapeutic obligation to offer optimal medical care to patients while conducting randomized controlled trials (RCTs). The appearance, however, is deceptive. In this article we argue that clinical equipoise is defective and incoherent in multiple ways. First, it conflates the sound methodological principle that RCTs should begin with an honest null hypothesis with the questionable ethical norm that participants in these trials should never be randomized (...) to an intervention known to be inferior to standard treatment. Second, the claim that RCTs preserve the therapeutic obligation of physicians misrepresents the patient-centered orientation of medical care. Third, the appeal to clinical equipoise as a basic principle of risk-benefit assessment for RCTs is incoherent. Finally, the difficulties with clinical equipoise cannot be resolved by viewing it as a presumptive principle subject to exceptions. In the final sections of the article, we elaborate on the non-exploitation framework for the ethics clinical research and indicate issues that warrant further inquiry. (shrink)