Medical Beneficence, Nonmaleficence, and Patients' Well-Being.

This article critically analyzes the principle of beneficence and the principle of nonmaleficence in clinical medical ethics. It resists some recent skepticism about the principle of nonmaleficence, and then seeks to explain its role in medicine. The article proposes that the two principles are informed by different accounts of what is in the patient's best interests. The principle of beneficence is tied to the patient's best overall interests, whereas the principle of nonmaleficence is tied to the patient's best medical interests only. The article argues that the principle of nonmaleficence takes priority over the principle of beneficence in that it filters the treatment options that are appropriately subject to the principle of beneficence. Understanding how both principles can play an important role in medical practice, and how they relate when they come into conflict, can help clinicians to avoid certain mistakes in thinking about their duties to their patients.

Weighted Lotteries and the Allocation of Scarce Medications for Covid-19.

The allocation of vaccines and therapeutics for Covid-19 obviously raises ethical questions, and physicians and ethicists have begun to address them. Writers have identified various criteria that should guide allocation decisions, but the criteria often conflict and need to be balanced against one another. This article proposes a model for thinking about how different considerations that are relevant to the distribution of vaccines and scarce treatments for Covid-19 could be integrated into an allocation procedure. The model employs the construct of a weighted lottery, which is a construct that has been employed in other contexts that involve the distribution of scarce resources. The article highlights the advantages of applying a weighted lottery to the Covid-19 context and offers an illustration for how it might work in practice. The primary aim of the article is to articulate the structural features of a weighted lottery for this context and to bring out its advantages over other methods for allocating Covid-19 medications.

Informed Consent, Therapeutic Misconception, and Unrealistic Optimism.

The Belmont Report attested to the cardinal importance of informed consent for ethical research on human subjects. Important challenges to securing informed consent have emerged since its publication more than 40 years ago. Among some of the most significant of these challenges are those that highlight social psychological factors that have the potential to impair the appreciation of relevant information disclosed in the informed consent process. Responding to these challenges requires us to think harder about the content of the principle of informed consent and the demands that it imposes on investigators. This article focuses on two challenges in particular, that presented by the so-called therapeutic misconception, and that presented by the psychological bias of unrealistic optimism. After outlining an account of the principle of informed consent as it applies to the research context, the article briefly reviews the empirical literature on the therapeutic misconception and the bias of unrealistic optimism. It then relates these phenomena to the principle of informed consent, paying special attention to the ethical demands they impose on investigators. The article concludes by considering how recent trends to integrate research and clinical care affect the main points it has advanced.

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.

Taking Respect Seriously: Clinical Research and the Demands of Informed Consent.

There is broad agreement among research ethicists that investigators have a duty to obtain the informed consent of all subjects who participate in their research trials. On a common view, the duty to obtain this informed consent follows from the need to respect persons and their autonomous decisions. However, the nature of informed consent and the demands it places on investigators are open to dispute and recently have been challenged. Respect for persons, it has been claimed, does not require investigators to guarantee that the subjects enrolled in their trials comprehend the risk/benefit information disclosed to them or even that they appreciate the difference between research and therapy. According to this critique, the significance of defects in informed consent, like therapeutic misconception or unrealistic optimism, has been greatly exaggerated. This article reevaluates informed consent in clinical research in light of this critique. It not only rebuts the main points the critics raise, but also shows that other points they raise can be accepted by a doctrine of informed consent that resembles the common view in maintaining that autonomous authorization is central to informed consent.

Reconsidering paternalism in clinical research.

The ethical standards that regulate clinical research have multiple rationales. Among them is the need to protect potential subjects from making imprudent decisions, which extends beyond the soft paternalistic concern to protect people from making uninformed decisions to participate in trials. This article argues that a plausible risk/benefit restriction on clinical trials is presumptively justified by hard paternalism, which in turn is supported by a deeper fairness-based rationale. This presumptive case for hard paternalism in research is not defeated by the alleged right to participate in clinical trials, by concerns about insult or status, by the need to conduct early phase trials that promise little to no benefit to participants, or by the recognition that some potential subjects are altruistically motivated.

Perceptions of control and unrealistic optimism in early-phase cancer trials.

PURPOSE: Recent research has found unrealistic optimism (UO) among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. METHODS: A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the bias in other contexts. RESULTS: One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators (p=0.024) and mental image (p=0.022), were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism (p<0.0001). CONCLUSION: Patient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing.

Variations in Unrealistic Optimism Between Acceptors and Decliners of Early Phase Cancer Trials.

Research has found that patient-subjects in early phase cancer trials exhibit unrealistic optimism regarding the risks and possible benefits of trial participation. Unrealistic optimism is associated with therapeutic misconception and failures to appreciate research-related information. This is the first study to assess whether those who decline to participate in these trials also exhibit unrealistic optimism. It is also the first study to assess whether there are significant differences in appreciation of research-related risks/benefits and therapeutic misconception between these two groups. We approached 261 patients at two academic medical centers who were offered enrollment in a Phase I, II, or I/II cancer trial (between 2012 and 2016). Two hundred thirty-three patients agreed to enroll in an early phase cancer trial, 171 of whom agreed to be interviewed for the study. Twenty-eight patients declined the offer to enroll, 15 of whom agreed to be interviewed for the study. Subjects participated in a structured face-to-face interview with a research associate trained to administer the study questionnaires. Acceptors demonstrated a significantly higher level of unrealistic optimism than decliners ( p < .05). Decliners had significantly less therapeutic misconception than acceptors (3.37 [ SD = 0.85] vs. 3.79 [ SD = 0.77], p = .042). There was a significant difference on one of the appreciation questions between acceptors and decliners ( p = .009). Comparative assessment of acceptors and decliners to early phase cancer trials casts light on whether unrealistic optimism is consequential for the decision to participate in these trials. The different levels of unrealistic optimism exhibited by these groups suggest that it may be a factor that affects the decision to participate.

Phase I Cancer Trials and Palliative Care: Antagonism, Irrelevance, or Synergy?

This article synthesizes the presentations and conclusions of an international symposium on Phase 1 oncology trials, palliative care, and ethics held in 2014. The purpose of the symposium was to discuss the intersection of three independent trends that unfolded in the past decade. First, large-scale reviews of hundreds of Phase I trials have indicated there is a relatively low risk of serious harm and some prospect of clinical benefit that can be meaningful to patients. Second, changes in the design and analysis of Phase I trials, the introduction of "targeted" investigational agents that are generally less toxic, and an increase in Phase I trials that combine two or more agents in a novel way have changed the conduct of these trials and decreased fears and apprehensions about participation. Third, the field of palliative care in cancer has expanded greatly, offering symptom management to late-stage cancer patients, and demonstrated that it is not mutually exclusive with disease-targeted therapies or clinical research. Opportunities for collaboration and further research at the intersection of Phase 1 oncology trials and palliative care are highlighted.

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

BACKGROUND: Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. METHODS: Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. RESULTS: Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. CONCLUSIONS: High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research.

Mindsets, informed consent, and research.

Study after study shows that subjects regularly overestimate the likelihood of gaining therapeutic benefit from a clinical trial. But more study is needed on why that mistake is common, and what it says about informed consent. Subjects may think about research differently at different phases in their participation.

Between beneficence and justice: the ethics of stewardship in medicine.

In an era of rapidly rising health care costs, physicians and policymakers are searching for new and effective ways to contain health care spending without sacrificing the quality of services provided. These proposals are increasingly articulated in terms of an ethical duty of stewardship. The duty of stewardship in medicine, however, is not at present well understood, and it is frequently conflated with other duties. This article presents a critical analysis of the notion of stewardship, which shows that it has an important and distinctive place in medical ethics. It claims that stewardship in medicine concerns the responsible use of a society's medical resources and it discusses the extent to which medical professionals are the proper stewards of these resources. The article argues that the duty of stewardship is best understood as a duty that applies in a space between the obligations of health care providers to provide beneficent care to their patients on the one hand and the obligations of citizens to bring about and support a just health care system on the other. Seen with clear eyes, stewardship in medicine is neither a consequence of beneficent medical care nor a substitute for justice.

Rethinking exploitation: a process-centered account.

Exploitation has become an important topic in recent discussions of biomedical and research ethics. This is due in no small measure to the influence of Alan Wertheimer's path-breaking work on the subject. This paper presents some objections to Wertheimer's account of the concept. The objections attempt to show that his account places too much emphasis on outcome-based considerations and too little on process-based considerations. Building on these objections, the paper develops an alternative process-centered account of the concept. This alternative account of exploitation takes as its point of departure the broadly Kantian notion that it is wrong to use another as an instrument for the advancement of one's own ends. It sharpens this slippery notion and adds a number of refinements to it. The paper concludes by arguing that process-centered accounts of exploitation better illuminate the ethical challenges posed by research on human subjects than outcome-centered accounts.

Two concepts of therapeutic optimism.

Researchers and ethicists have long been concerned about the expectations for direct medical benefit expressed by participants in early phase clinical trials. Early work on the issue considered the possibility that participants misunderstand the purpose of clinical research or that they are misinformed about the prospects for medical benefit from these trials. Recently, however, attention has turned to the possibility that research participants are simply expressing optimism or hope about their participation in these trials. The ethical significance of this therapeutic optimism remains unclear. This paper argues that there are two distinct phenomena that can be associated with the term 'therapeutic optimism'-one is ethically benign and the other is potentially worrisome. Distinguishing these two phenomena is crucial for understanding the nature and ethical significance of therapeutic optimism. The failure to draw a distinction between these phenomena also helps to explain why different writers on the topic often speak past one another.