Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain (...) principally to individual participants: providing transparency; allowing control and authorization; promoting concordance with participants' values; and protecting and promoting welfare interests. Three other functions are systemic or policy focused: promoting trust; satisfying regulatory requirements; and promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals. (shrink)
Classic statements of research ethics advise against permitting physician-investigators to obtain consent for research participation from patients with whom they have preexisting treatment relationships. Reluctance about “dual-role” consent reflects the view that distinct normative commitments govern physician–patient and investigator–participant relationships, and that blurring the research–care boundary could lead to ethical transgressions. However, several features of contemporary research demand reconsideration of the ethics of dual-role consent. Here, we examine three arguments advanced against dual-role consent: that it creates role conflict for the (...) physician-investigator; that it can compromise the voluntariness of the patient-participant’s consent; and that it promotes therapeutic misconceptions. Although these concerns have merit in some circumstances, they are not dispositive in all cases. Rather, their force—and the ethical acceptability of dual-role consent—varies with features of the particular study. As research participation more closely approximates usual care, it becomes increasingly acceptable, or even preferable, for physicians to seek consent for research from their own patients. It is time for a more nuanced approach to dual-role consent. (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.
We conducted focus groups to assess patient attitudes toward research on medical practices in the context of usual care. We found that patients focus on the implications of this research for their relationship with and trust in their physicians. Patients view research on medical practices as separate from usual care, demanding dissemination of information and in most cases, individual consent. Patients expect information about this research to come through their physician, whom they rely on to identify and filter associated risks. (...) In general, patients support this research, but worry that participation in research involving randomization may undermine individualized care that acknowledges their unique medical histories. These findings suggest the need for public education on variation in practice among physicians and the need for a collaborative approach to the governance of research on medical practices that addresses core values of trust, transparency, and partnership. (shrink)
The use of brain imaging technology as a common tool of research has spawned concern and debate over how investigators should respond to incidental fndings discovered in the course of research. In this article, we argue that investigators have an obligation to respond to incidental fndings in view of their entering into a professional relationship with research participants in which they are granted privileged access to private information with potential relevance to participants' health. We discuss the scope and limits of (...) this professional obligation to respond to incidental fndings, bearing in mind that the relationship between investigators and research participants differs fundamentally from the doctor-patient relationship. (shrink)
The shift away from paternalistic decision-making and toward patient-centered, shared decision-making has stemmed from the recognition that in order to practice medicine ethically, health care professionals must take seriously the values and preferences of their patients. At the same time, there is growing recognition that minor and seemingly irrelevant features of how choices are presented can substantially influence the decisions people make. Behavioral economists have identified striking ways in which trivial differences in the presentation of options can powerfully and predictably (...) affect people's choices. Choice-affecting features of the decision environment that do not restrict the range of choices or significantly alter the incentives have come to be known as “nudges.” Although some have criticized conscious efforts to influence choice, we believe that clinical nudges may often be morally justified. The most straightforward justification for nudge interventions is that they help people bypass their cognitive limitations—for example, the tendency to choose the first option presented even when that option is not the best for them—thereby allowing people to make choices that best align with their rational preferences or deeply held values. However, we argue that this justification is problematic. We argue that, if physicians wish to use nudges to shape their patients’ choices, the justification for doing so must appeal to an ethical and professional standard, not to patients’ preferences. We demonstrate how a standard with which clinicians and bioethicists already are quite familiar—the best-interest standard—offers a robust justification for the use of nudges. (shrink)
Large-scale sequencing tests, including whole-exome and whole-genome sequencing, are rapidly moving into clinical use. Sequencing is already being used clinically to identify therapeutic opportunities for cancer patients who have run out of conventional treatment options, to help diagnose children with puzzling neurodevelopmental conditions, and to clarify appropriate drug choices and dosing in individuals. To evaluate and support clinical applications of these technologies, the National Human Genome Research Institute and National Cancer Institute have funded studies on clinical and research sequencing under (...) the Clinical Sequencing Exploratory Research program as well as studies on return of results. Most of these studies use sequencing in real-world clinical settings and collect data on both the application of sequencing and the impact of receiving genomic findings on study participants. They are occurring in the context of controversy over how to obtain consent for exome and genome sequencing. (shrink)
Mounting evidence suggests that participation in clinical trials confers neither advantage nor disadvantage on those enrolled. Narrow focus on the question of a “trial effect,” however, distracts from a broader mechanism by which patients may benefit from ongoing clinical research. We hypothesize that the existence of clinical trials infrastructure—the organizational culture, systems, and expertise that develop as a product of sustained participation in cooperative clinical trials research—may function as a quality improvement lever, improving the quality of care and outcomes of (...) all patients within an institution or region independent of their individual participation in trials. We further contend that this “infrastructure effect” can yield particular benefits for patients in low- and middle-income countries. The hypothesis of an infrastructure effect as a quality improvement intervention, if correct, justifies enhanced research capacity in LMIC as a pillar of health system development. (shrink)
As sharing and secondary research use of biospecimens increases, IRBs and researchers face the challenge of protecting and respecting donors without comprehensive regulations addressing the human subject protection issues posed by biobanking. Variation in IRB biobanking policies about these issues has not been well documented.
We argue that charging people to participate in research is likely to undermine the fundamental ethical bases of clinical research, especially the principles of social value, scientific validity, and fair subject selection.
Ethical concerns have been raised about the quality of informed consent by participants in phase 1 oncology trials. Interview surveys indicate that substantial proportions of trial participants do not understand the purpose of these trials—evaluating toxicity and dosing for subsequent efficacy studies—and overestimate the prospect of therapeutic benefit that they offer. In this article we argue that although these data suggest the desirability of enhancing the process of information disclosure and assessment of comprehension of the implications of study participation, they (...) do not necessarily invalidate consent by phase 1 trial participants. (shrink)
The COVID-19 pandemic has forced clinicians, policy-makers and the public to wrestle with stark choices about who should receive potentially life-saving interventions such as ventilators, ICU beds and dialysis machines if demand overwhelms capacity. Many allocation schemes face the question of whether to consider age. We offer two underdiscussed arguments for prioritising younger patients in allocation policies, which are grounded in prudence and fairness rather than purely in maximising benefits: prioritising one’s younger self for lifesaving treatments is prudent from an (...) individual perspective, and prioritising younger patients works to narrow health disparities by giving priority to patients at risk of dying earlier in life, who are more likely to be subject to systemic disadvantage. We then identify some confusions in recent arguments against considering age. (shrink)
In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated (...) animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health, based upon recommendations in an influential 2011 Institute of Medicine report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people. (shrink)
: The "therapeutic misconception," described by Paul Appelbaum and colleagues more than 20 years ago, refers to the tendency of participants in clinical trials to confuse the design and conduct of research with personalized medical care. Although the "therapeutic misconception" has become a term of art in research ethics, little systematic attention has been devoted to the ethical significance of this phenomenon. This article examines critically the way in which Appelbaum and colleagues formulate what is at stake in the therapeutic (...) misconception, paying particular attention to assumptions and implications that clinical trial participation disadvantages research participants as compared with receiving standard medical care. After clarifying the ethical significance of the therapeutic misconception with respect to the decision making of patients, we offer policy recommendations for obtaining informed consent to participation in clinical trials. (shrink)
The contemporary system of prospective oversight of human subjects research has been criticized as inefficient and ineffective. Plausible approaches to research oversight range from no prospective review, to review-and-comment, to the current review-and-approve regime. Articulating this spectrum offers an opportunity to consider systematically the strengths and disadvantages of each.
The random]ized clinical trial is widely accepted as the optimal approach to evaluating the safety and efficacy of medical treatments. Resistance to randomized treatment assignment arises regularly, most commonly in situations where the disease is life-threatening and treatments are either unavailable or unsatisfactory. Historical control designs, in which all participants receive the experimental treatment with results compared to a prior cohort, are advocated by some as more ethical in such circumstances; however, such studies are often highly biased in favor of (...) the new treatment and frequently yield misleading results. Alternative controlled designs motivated by the desire to maximize the number of patients with the treatment ultimately determined to be superior have been proposed, but have been challenged on both methodological and ethical grounds. Debates about appropriate and ethical study designs recurred during the recent Ebola Virus Disease epidemic in West Africa. Despite its devastating nature, the EVD epidemic showed the ongoing necessity of conducting randomized trials to obtain convincing evidence of the safety and efficacy of therapeutic interventions. (shrink)
Over the past 40 years, a complex review and oversight system has grown within the United States and internationally to regulate the conduct of human subjects research. This system developed in response to revelations of abuses of human subjects in experiments such as those conducted in the Nazi concentration camps, the Tuskegee Study of Untreated Syphilis in the Negro Male, the Willowbrook Hepatitis Studies, and the studies described by Beecher in his 1966 article in the New England Journal of Medicine. (...) The oversight system is based on a foundation, first implemented by the U.S. Public Health Service in 1966 and by the U.S. Food and Drug Administration in 1971, of prior review and approval of a written experimental protocol by an independent committee. The World Medical Association articulated the ethical centrality of independent review in its 1975 revision of the Declaration of Helsinki, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research endorsed the requirement in its flagship Belmont Report. (shrink)
Public disclosure of industry payments to physicians is one way to address financial conflicts of interest in medicine. As part of the Patient Protection and Affordable Care Act, the Physician Payment Sunshine Act requires pharmaceutical, medical device, and biologics manufacturers who have at least one product reimbursed by Medicare or Medicaid to disclose payments to physicians and teaching hospitals on a public website starting in 2014. The physician payment data will contain individual physician names, monetary values, and specific products connected (...) to payments.According to the Final Regulations issued by the Centers for Medicare and Medicaid Services in February 2013, the law will make transparent the extent and nature of relationships between physicians, teaching hospitals, and manufacturers. (shrink)
One of the central ethical tenets of research in developing countries is the sponsor's obligation to benefit host participants and communities. Two known models of benefits provision dominate the ethical discourse of research in developing countries. The first model, known as the “reasonable availability,” endorses the obligation to provide interventions proven to be effective at the end of a study. This contrasts with the second model, known as “fair benefits,” which endorses other forms of benefits that host communities may deem (...) as fair beyond those derived directly from the study's findings. This paper explores a third benefit model consistent with the writings of the Human Hereditary and Health in Africa research initiative. The H3Africa—a North-South collaborative initiative predicated by U.S. National Institutes of Health, the Wellcome Trust and the African Society of Human Genetics upholds a benefit model that endorses capacity building as the primary obligation of its research agenda. This is evident by the endorsement of mechanisms to strengthen capacity building in its research projects. While capacity building remains a plausible means of improving the expertise, quality and independence of research in Africa, sustainable measures are needed to realizing the full potential for African-led research on the continent. (shrink)
ObjectiveTo evaluate the relationship between recently trained paediatricians' ethics knowledge and exposure to a formal ethics or professionalism curriculum during residency.MethodsWe conducted a cross-sectional survey of recently trained paediatricians which included a validated 23-item instrument called the Test of Residents' Ethics Knowledge for Pediatrics. The sample included paediatricians who completed medical school in 2006–2008, whose primary specialty was paediatrics or a paediatric subspecialty, and who completed paediatric residency training in 2010–2011. This sample was stratified based on residency programme variables: presence (...) of a formal curriculum in ethics or professionalism, programme size and American Board of Pediatrics certifying exam passage rate. Paediatricians were randomly selected from each stratum for survey participation.ResultsAmong the 370 responding paediatricians, the mean knowledge score was 17.3 out of a possible 23. Presence of a formal curriculum in ethics and/or professionalism was not significantly associated with knowledge. Knowledge was lowest on items about parental requests for a child to undergo genetic testing, preserving patient confidentiality over email, decision-making regarding life-sustaining technologies, and decision-making principles such as assent and parental permission.ConclusionsThis study highlights several areas in which paediatricians' knowledge may be low and that are amenable to targeted educational interventions. These findings should prompt discussion and research among ethicists and educators about how ethics and professionalism curricula can more consistently influence paediatricians' knowledge. (shrink)
: Originally presented during Ethic Rounds at the Dana-Farber Cancer Institute, this commentary on the case of a patient treated for life-threatening cancer explores the responsibilities of health care providers when addressing the patient's desire to adopt a child.
The conflicts of interest that may arise in relationships between academic researchers and industry continue to prompt controversy. The bulk of attention has focused on financial aspects of these relationships, but conflicts may also arise in the legal obligations that faculty acquire through consulting contracts. However, oversight of faculty members' consulting agreements is far less vigorous than for financial conflicts, creating the potential for faculty to knowingly or unwittingly contract away important rights and freedoms. Increased regulation could prevent this, but (...) it is unclear what forms of oversight universities view as feasible and effective. In this article, we report on a Delphi study to evaluate several approaches for oversight of consulting agreements by medical schools. The panel was comprised of 11 senior administrators with responsibility for oversight of faculty consulting relationships. We found broad agreement among panelists regarding the importance of institutional oversight to protect universities' interests. There was strong support for two specific approaches: providing educational resources to faculty and submitting consulting agreements for institutional review. Notwithstanding the complexities of asserting authority to regulate private consulting agreements between faculty members and companies, medical school administrators reached consensus that several approaches to improving institutional oversight are feasible and useful. (shrink)
In most U.S. jurisdictions, clinicians providing informal “curbside” consults are protected from medical malpractice liability due to the absence of a doctor-patient relationship. A recent Minnesota Supreme Court case, Warren v. Dinter, offers the opportunity to reassess whether the majority rule is truly serving the best interests of patients.