Randomization is the “gold standard” design for clinical research trials and is accepted as the best way to reduce bias. Although some controversy remains over this matter, we believe equipoise is the fundamental ethical requirement for conducting a randomized clinical trial. Despite much attention to the ethics of randomization, the moral psychology of this study design has not been explored. This article analyzes the ethical tensions that arise from conducting these studies and examines the moral psychology of this design from (...) the perspectives of physician-investigators and patient-subjects. We conclude with a discussion of the practical implications of this analysis. (shrink)

The foundations of research ethics are riven with fault lines emanating from a fear that if research is too closely connected to weighty social purposes an imperative to advance the common good through research will justify abrogating the rights and welfare of study participants. The result is an impoverished conception of the nature of research, an incomplete focus on actors who bear important moral responsibilities, and a system of ethics and oversight highly attuned to the dangers of research but largely (...) silent about threats of ineffective, inefficient, and inequitable medical practices and health systems. -/- In For the Common Good: Philosophical Foundations of Research Ethics, Alex John London defends a conception of the common good that grounds a moral imperative with two requirements. The first is to promote research that generates the information necessary to enable key social institutions to effectively, efficiently, and equitably safeguard the basic interests of individuals. The second is to ensure that research is organized as a voluntary scheme of social cooperation that respects its various contributors' moral claims to be treated as free and equal. Connecting research to the goals of a just social order grounds a framework for assessing and managing research risk that reconciles these requirements and justifies key oversight practices in non-paternalistic terms. Reconceiving research ethics as resolving coordination problems and providing credible assurance that these requirements are being met expands the issues and actors that fall within the purview of the field and provides the foundation for a more unified and coherent approach to domestic and international research. -/- This is an open access title available under the terms of a CC BY-NC-ND 4.0 license. It is free to read at Oxford Scholarship Online and offered as a free PDF download from OUP and selected open access locations. (shrink)

The physician-researcher conflict of interest, a long-standing and widely recognized ethical challenge of clinical research, has thus far eluded satisfactory solution. The conflict is fairly straightforward. Medical research and medical therapy are distinct pursuits; the former is aimed at producing generalizable knowledge for the benefit of future patients, whereas the latter is aimed at addressing the individualized medical needs of a particular patient. When the physician-researcher combines these pursuits, he or she serves two masters and cannot — no matter how (...) well-intentioned — avoid the risk of compromising the duties owed in one of the professional roles assumed. Because of the necessary rigidity of a research protocol, the more demanding of the two masters is frequently the research.The problem of the physician-researcher conflict has been evident since the first attempts to regulate human research in the United States. Otto E. Guttentag, a physician at the University of California School of Medicine in San Francisco, addressed the conflict in a 1953Sciencemagazine article. (shrink)

Conflicts of interest have been reduced to financial conflicts. The National Institutes of Health’s new rules for managing conflicts of interest in medical research, the first major change to the regulations in over 15 years, address only financial ties. Although several commentators urged that the regulations also cover non-financial interests, the Department of Health and Human Services declined to do so. Similarly, the Institute of Medicine’s influential 2009 Conflict of Interest Report focuses almost exclusively on financial conflicts. Institutional policies at (...) academic medical centers and guidance from professional bodies and medical journals also primarily emphasize financial ties. Even broadly worded rules are applied more readily to financial ties than non-financial interests, such as the regulations that restrict institutional review board members with conflicting interests from participating in protocol reviews. (shrink)

Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the exception of self-experimentation, limits on (...) research risks faced by healthy volunteers constitute a type of soft, impure paternalism because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and that the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks. (shrink)

Valid Informed consent to medical treatment or research participation has traditionally been viewed as consisting of the following requirements: the person has t...

The idea that payment for research participation can be coercive appears widespread among research ethics committee members, researchers, and regulatory bodies. Yet analysis of the concept of coercion by philosophers and bioethicists has mostly concluded that payment does not coerce, because coercion necessarily involves threats, not offers. In this article we aim to resolve this disagreement by distinguishing between two distinct but overlapping concepts of coercion. Consent-undermining coercion marks out certain actions as impermissible and certain agreements as unenforceable. By contrast, (...) coercion as subjection indicates a way in which someone’s interests can be partially set back in virtue of being subject to another’s foreign will. While offers of payment do not normally constitute consent-undermining coercion, they do sometimes constitute coercion as subjection. We offer an analysis of coercion as subjection and propose three possible practical responses to worries about the coerciveness of payment. (shrink)

When seriously ill patients for whom existing treatments are inadequate are invited to participate in clinical trials that offer a new treatment, should those persons be considered “vulnerable”? And if so, what additional protections should they be accorded? This article attempts to provide some answers.

Suppose that someone has a serious illness. The illness will likely lead to significant disabilities, and may even cause death. Existing treatments are unsatisfactory. The patient learns about a clinical trial, in which some allegedly promising new treatment for that illness is being tested.Such seriously ill patients for whom existing treatments are unsatisfactory have sometimes been categorized as medically vulnerable in the literature. Should these patients indeed be considered vulnerable subjects and be provided with special protections? And if the answer (...) is yes, then what are those special protections? This article explores the possible answers to these questions.The federal regulations for the protection of research subjects have several provisions addressing the concept of vulnerability. The three subparts Subparts B, C, and D deal with specific categories of vulnerable subjects, but do relatively little to address broader issues relating to vulnerability that might apply to a category such as the medically vulnerable. The Common Rule is the only section containing general discussions of vulnerability. (shrink)

Data Safety and Monitoring Boards have been referred to as a “growth industry,” and this trend continues to be fueled by recent FDA guidance and the NIH's requirement that DSMBs be employed in virtually all phase III clinical trials. The widening role of DSMBs has been sporadically questioned on ethical grounds, but growth has continued, despite the fact that many of the questions endure, unanswered, save for repeated references to safeguarding the scientific integrity of trials. This may be about to (...) change. The recently appointed director of the Office for Human Research Protections , Jerry Menikoff, is on record as regarding current practices — where consent forms often promise what the DSMB has been assembled to specifically not provide — as constituting fraudulent behavior. That is, a subject may inherently rely on, to their detriment, information that has been misrepresented in the consent document. In this paper, we assemble some of the enduring questions and top them off with Menikoff's tour de force to present what we hope will be a compelling argument to require that consent forms fairly represent what the DSMB will do — and not do — with trial data as they accumulate. We argue that DSMBs should be used only in rare circumstances, and question the practice of precluding principal investigators from DSMB membership, but our main thrust is to ensure that DSMBs, when used at all, are properly described in trial consent forms. (shrink)

Data Safety and Monitoring Boards were introduced in the 1960s to monitor data in clinical trials to ensure subject safety. It was thought important that DSMB members be experts in the field of interest, but not otherwise involved in the study in order to maximize objectivity. Since then, the use of DSMBs has increased dramatically, and their scope has expanded to include scientific issues — in particular, to avoid bias that can result when trials are stopped early because of evidence (...) that one treatment has greater efficacy or causes greater harm than another; or that no treatment is likely to do better than any other. (shrink)

What the Doctor Didn’t Say, by Jerry Menikoff and Edward P. Richards, is a courageous and well-written volume that examines some of the fundamental debates pertaining to the ethics of clinical research. The volume deserves a careful reading by anyone with a potential role in clinical research: clinicians who might serve as investigators or refer patients to clinical trials; research staff; Institutional Review Board members and administrators; sponsors who design clinical trials; and the book’s intended audience, namely, potential research participants (...) and their families. A cursory reading of this volume might lead one to think that Menikoff and Richards have declared war on clinical research. They have not. Instead, they offer an in-depth study of the conduct and oversight of clinical research through the lens of law and ethics. They shed light on old issues and initiate discussion of new questions, challenging readers to think critically about the relationship between medical ethics, research ethics, the law, and the conduct of clinical research. (shrink)

What the Doctor Didn’t Say, by Jerry Menikoff and Edward P. Richards, is a courageous and well-written volume that examines some of the fundamental debates pertaining to the ethics of clinical research. The volume deserves a careful reading by anyone with a potential role in clinical research: clinicians who might serve as investigators or refer patients to clinical trials; research staff; Institutional Review Board members and administrators; sponsors who design clinical trials; and the book’s intended audience, namely, potential research participants (...) and their families. A cursory reading of this volume might lead one to think that Menikoff and Richards have declared war on clinical research. They have not. Instead, they offer an in-depth study of the conduct and oversight of clinical research through the lens of law and ethics. They shed light on old issues and initiate discussion of new questions, challenging readers to think critically about the relationship between medical ethics, research ethics, the law, and the conduct of clinical research. (shrink)

Twenty-five years after the term "therapeutic misconception’ (TM) first entered the literature, most commentators agree that it remains widespread. However, the majority of scholarly attention has focused on the reasons why a patient cum human subject might confuse the goals of research with the goals of therapy. Although this paper addresses the social and cultural factors that seem to animate the TM among subjects, it also fills a niche in the literature by examining why investigators too might operate under a (...) similar confusion. In framing these issues, the paper expressly adopts a Wittgensteinian approach to evaluating the TM, suggesting that interlocutors do not need any analytic definition of the TM to use the term meaningfully in thinking about the moral implications of the TM in practice. (shrink)

In the article “Informed Consent: What Must be Disclosed and What Must be Understood?” Joseph Millum and Danielle Bromwich argue that informed consent requires satisfaction of certain disclosure an...

The conception of the doctor–patient relationship under Australian law has followed British common law tradition whereby the relationship is founded in a contractual exchange. By contrast, this article presents a rationale and framework for an alternative model—a “Trust Model”—for implementation into law to more accurately reflect the contemporary therapeutic dynamic. The framework has four elements: an assumption that professional conflicts with patient safety, motivated by financial or personal interests, should be avoided; an onus on doctors to disclose these conflicts; a (...) proposed mechanism to contend with instances where doctors choose not to disclose; and sanctions for non-compliance with the regime. (shrink)