The Use of Authorized Concealment to Minimize Nocebo Side Effects: A Survey of US Public Attitudes.

INTRODUCTION: To minimize nocebo effects, it may be possible to employ authorized concealment, in which clinicians tell patients about the nocebo phenomenon and ask if they would prefer not to be informed about mild treatment side effects. OBJECTIVE: The objective of the study was to understand public evaluations of authorized concealment for reducing nocebo effects. METHODS: An online cross-sectional survey was completed by a demographically diverse US national community sample between June 2 and 6, 2023. Participants were 1,012 adults residing in 48 states, ages ranging from 18 to 94 (mean = 43.2), 65.4% regularly taking medication, and 66.6% reporting a chronic physical or mental health condition. After learning about nocebo effects, participants rated and estimated their likelihood of consenting to four potential methods for authorized concealment of mild side effects. The four methods were ranked for preference and ranked again with the options of (1) receiving all side-effect information and (2) having the opportunity to select among disclosure methods. RESULTS: A majority of participants (86.2%) positively endorsed at least one authorized concealment method and 88.2% estimated they would consent to at least one method. Authorized concealment in which individuals learned only the most common side effects or had side-effect information available online received more positive ratings and rankings. A final ranking yielded preferences for receiving all side-effect information (30.4%) and having the opportunity to select side-effect disclosure method (31.8%). CONCLUSIONS: Our study suggests that many in the public could be open to authorized concealment for mild side effects when it is explained in reference to nocebo effects.

Current Practice Diagnosing Brain Death Is Not Consistent With Legal Statutes Requiring the Absence of All Brain Function.

The legal standard for the determination of death by neurologic criteria in the United States is laid out in the Uniform Determination of Death Act (UDDA), which requires the irreversible cessation of all functions of the entire brain. Most other nations endorse a "whole-brain" standard as well. However, current practice in the determination of death by neurologic criteria is not consistent with this legal standard, because some patients who are diagnosed as brain-dead, in fact retain some brain function, or retain the capacity for the return of some brain function. In response, the American Academy of Neurology published updated guidelines, which assert that hypothalamic function is consistent with the neurological standard enshrined in the UDDA. Others have suggested that it is an open question whether the hypothalamus and pituitary are part of "the entire brain," as delineated in the UDDA. While we agree that determination of death practices are worthy of continued dialogue and refinement in practice that dialogue must adhere to reasonable standards of logic and scientific accuracy.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Challenge Experiments in Nonhuman Primates: An Ethical Perspective.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated massive investment in biomedical research with the aims of understanding the disease and developing effective vaccine and therapeutic interventions. What role should animal research play in this scientific endeavor? Both the urgency to evaluate candidate interventions for human use and growing societal concern about ethical treatment of (nonhuman) animals put into question the justifiability of animal research as a precursor to clinical trials. Yet forgoing animal research in the rush to undertake human testing might expose human research participants to unacceptable risks. In this article, we apply a recently developed framework of principles for animal research ethics in exploring ethical questions raised by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection challenge experiment involving rhesus macaques, which evaluated the protective efficacy of the mRNA-1273 vaccine that was recently approved for emergency use. Our aim is to illuminate the ethical issues while introducing, and illustrating the use of, the framework.

Allocating a COVID-19 Vaccine: Balancing National and International Responsibilities.

Policy Points In this paper we propose a middle-ground policy for the distribution of an effective COVID-19 vaccine, between a cosmopolitan approach that rejects entirely nation-state priority and unbridled vaccine nationalism that disregards obligations to promote an equitable global allocation of an effective vaccine over time. Features of the COVAX partnership, a collaboration among the Global Alliance for Vaccines and Immunizations (GAVI), the Coalition for Epidemic Preparedness Innovations (CEPI), and the World Health Organization (WHO) to develop and distribute COVID-19 vaccines make it an appropriate framework for a middle-ground policy.

Liberty and Protection of Society During a Pandemic: Revisiting John Stuart Mill.

John Stuart Mill's classic text, On Liberty, maps the scope and limits on individual freedom. His "harm principle"-that liberty can be legitimately restricted by government or society only to prevent harm to others-has had a great influence on contemporary public health ethics. This essay examines Mill's philosophy of liberty as it pertains to public health interventions in response to the coronavirus pandemic. Particular applications include examination of face masks, lockdowns, and mandatory vaccination.

The Legality and Ethics of Mandating COVID-19 Vaccination.

In light of ongoing concerns in the US that COVID-19 vaccine uptake is stagnating and that cases remain high amongst the unvaccinated, there is growing interest in increasing uptake by mandating vaccination. COVID-19 vaccine mandates must be understood and assessed in terms of who is requiring vaccination and who is required to be vaccinated. This essay considers the legal and ethical implications of states mandating vaccination for children and adults, as well as of employers mandating vaccines for employees. We conclude that COVID-19 vaccine mandates are legally and ethically permissible.

Bioethics as a Vocation.

This essay offers practical guidance for the activity of bioethics scholarship in the form of maxims or rules of thumb, explicated by the author's work in bioethics research, mentoring, peer review, and journal editing. It is organized into three sections: (1) education, (2) seeking ideas for projects, and (3) writing papers.

Revisiting the Distinction and the Connection Between Research and Practice.

The Belmont Report addresses the distinction between practice and research as guidance for which activities should be evaluated prospectively by a research ethics committee. This essay argues that the distinction between clinical practice and clinical research has a more fundamental significance for understanding the ethics of clinical research. After discussing the important connections between clinical research and clinical practice, the essay examines in detail ethically significant differences between these two sorts of activities. This sets the stage for a critique of clinical equipoise, widely regarded as a fundamental principle of clinical research ethics.

Drawing the line on physician-assisted death.

Drawing the line on physician assistance in physician-assisted death (PAD) continues to be a contentious issue in many legal jurisdictions across the USA, Canada and Europe. PAD is a medical practice that occurs when physicians either prescribe or administer lethal medication to their patients. As more legal jurisdictions establish PAD for at least some class of patients, the question of the proper scope of this practice has become pressing. This paper presents an argument for restricting PAD to the terminally ill that can be accepted by defenders as well as critics of PAD for the terminally ill. The argument appeals to fairness-based paternalism and the social meaning of medical practice. These two considerations interact in various ways, as the paper explains. The right way to think about the social meaning of medical practice bears on fair paternalism as it relates to PAD and vice versa. The paper contends that these considerations have substantial force when directed against proposals to extend PAD to non-terminally ill patients, but considerably less force when directed against PAD for the terminally ill. The paper pays special attention to the case of non-terminally ill patients who suffer from treatment-resistant depression, as these patients present a potentially strong case for extending PAD beyond the terminally ill.

On Collaboration in Bioethics Scholarship.

In this essay, I reflect on a career largely devoted to collaborative scholarship in bioethics. I describe the process of collaborative research and writing, including the mentorship collaboration, and discuss ethical issues posed by collaborative scholarship.

Are Patients With Cancer Best Managed in a Clinical Trial?

This Viewpoint analyzes how the NCCN's boxed statement that all cancer is best managed in a clinical trial cannot be applied to all patients and calls for its removal from its clinical practice guidelines.

Reining in the Placebo Effect.

What is known as the "placebo effect" has received increasing attention in recent years in scientific investigation and the news media. The concept of the placebo effect, however, is subject to confusion and misleading implications, especially when applied broadly. This essay argues that it is desirable to confine the concept, as applied to biomedicine, to the therapeutic effects of deliberate placebo interventions. The author examines in detail the conceptual problems in characterizing the therapeutic benefits that flow from communication in the clinician-patient relationship as placebo effects.

Medical Futility and "Brain Death".

Judgments of futility are always relative to some goal. In light of that proposition, continued treatment for those diagnosed as "brain dead" is not necessarily futile.

Advice and care for patients who die by voluntarily stopping eating and drinking is not assisted suicide.

BACKGROUND: A competent patient has the right to refuse foods and fluids even if the patient will die. The exercise of this right, known as voluntarily stopping eating and drinking (VSED), is sometimes proposed as an alternative to physician assisted suicide. However, there is ethical and legal uncertainty about physician involvement in VSED. Are physicians advising of this option, or making patients comfortable while they undertake VSED, assisting suicide? This paper attempts to resolve this ethical and legal uncertainty. DISCUSSION: The standard approach to resolving this conundrum has been to determine whether VSED itself is suicide. Those who claim that VSED is suicide invariably claim that physician involvement in VSED amounts to assisting suicide. Those who claim that VSED is not suicide claim that physician involvement in VSED does not amount to assisting suicide. We reject this standard approach. CONCLUSION: We instead argue that, even if VSED is classified as a kind of suicide, physician involvement in VSED is not a form of assisted suicide. Physician involvement in VSED does not therefore fall within legal provisions that prohibit VSED.

Do the 'brain dead' merely appear to be alive?

The established view regarding 'brain death' in medicine and medical ethics is that patients determined to be dead by neurological criteria are dead in terms of a biological conception of death, not a philosophical conception of personhood, a social construction or a legal fiction. Although such individuals show apparent signs of being alive, in reality they are (biologically) dead, though this reality is masked by the intervention of medical technology. In this article, we argue that an appeal to the distinction between appearance and reality fails in defending the view that the 'brain dead' are dead. Specifically, this view relies on an inaccurate and overly simplistic account of the role of medical technology in the physiology of a 'brain dead' patient. We conclude by offering an explanation of why the conventional view on 'brain death', though mistaken, continues to be endorsed in light of its connection to organ transplantation and the dead donor rule.

Challenging the Conventional Wisdom: From Philosophy to Bioethics.

Philosophy is a core discipline that has contributed importantly to bioethics. In this essay, the author traces his trajectory from philosophy to bioethics, oriented around the theme of challenging the conventional wisdom. Three topics are discussed to illustrate this theme: the ethics of randomized trials, determination of death and organ transplantation, and pragmatism as a method of bioethics. In addition, the author offers some general reflections on the relationship between philosophy and bioethics. Philosophy recovers itself when it ceases to be a device for dealing with the problems of philosophers and becomes a method, cultivated by philosophers, for dealing with the problems of men.-John Dewey (1917).

Reframing Consent for Clinical Research: A Function-Based Approach.

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: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals.

The Ethics of Clinical Trials Research in Severe Mood Disorders.

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are highly prevalent, frequently disabling, and sometimes deadly. Additional research and more effective medications are desperately needed, but clinical trials research in mood disorders is fraught with ethical issues. Although many authors have discussed these issues, most do so from a theoretical viewpoint. This manuscript uses available empirical data to inform a discussion of the primary ethical issues raised in mood disorders research. These include issues of consent and decision-making capacity, including patients' motivations for participating in research. We also address drug withdrawals, placebo controls, and the overall safety of research. Finally, we examine the extant literature for studies discussing potential indirect benefits of clinical trials research to participants. Taken together, the evidence suggests that clinical trials research incorporating drug withdrawals and placebo controls can be conducted safely and ethically, even in patients with severe or treatment-resistant mood disorders. In fact, given the dearth of effective treatment options for this population, it is our opinion that a moral imperative exists to extend the offer of research participation to severely ill or treatment-resistant groups.

Ethical Rationale for the Ebola "Ring Vaccination" Trial Design.

The 2014 Ebola virus epidemic is the largest and most severe ever recorded. With no approved vaccines or specific treatments for Ebola, clinical trials were launched within months of the epidemic in an unprecedented show of global partnership. One of these trials used a highly innovative "ring vaccination" design. The design was chosen for operational, scientific, and ethical reasons--in particular, it was regarded as ethically superior to individually randomized placebo-controlled trials. We scrutinize the ethical rationale for the ring vaccination design. We argue that the ring vaccination design is ethical but fundamentally equivalent to placebo-controlled designs with respect to withholding a potentially effective intervention from the control group. We discuss the implications for the ongoing ring vaccination trial and future research.