Some early phase clinical studies of candidate HIV cure and remission interventions appear to have adverse medical risk–benefit ratios for participants. Why, then, do people participate? And is it ethically permissible to allow them to participate? Recent work in decision theory sheds light on both of these questions, by casting doubt on the idea that rational individuals prefer choices that maximise expected utility, and therefore by casting doubt on the idea that researchers have an ethical obligation not to enrol participants (...) in studies with high risk–benefit ratios. This work supports the view that researchers should instead defer to the considered preferences of the participants themselves. This essay briefly explains this recent work, and then explores its application to these two questions in more detail. (shrink)

Suppose that A and B are two kinds of goods such that more of each is better than less. A is strongly superior to B if any amount of A is better than any amount of B. It is weakly superior to B if some amount of A is better than any amount of B. There are many examples of these relations in the literature, sometimes under the labels “higher goods” and “discontinuity.” The chapter gives a precise and generalized statement (...) of Strong and Weak Superiority and discusses different ways in which these relations can be relevant to the aggregation of welfare. It also proves a number of general results. One of the results gives rise to a dilemma: It can be used as an argument against the existence of value superiority or, alternatively, as an argument against the view that superiority entails a radical difference in value. (shrink)

One of the key ethical requirements for biomedical research is that it have an acceptable risk-benefit profile (Emanuel, Wendler, and Grady 2000). The International Conference of Harmonization guidelines mandate that clinical trials should be initiated and continued only if “the anticipated benefits justify the risks” (1996). Guidelines from the Council for International Organizations of Medical Sciences state that biomedical research is acceptable only if the “potential benefits and risks are reasonably balanced” (2002). U.S. federal regulations require that the “risks to (...) subjects” be “reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge” to be gained from the .. (shrink)

Modern antiretroviral therapies are capable of suppressing HIV in the bloodstream to undetectable levels. Nonetheless, people living with HIV must maintain lifelong adherence to ART to avoid the re-emergence of the infection. So despite the existence and efficacy of ART, there is still substantial interest in development of a cure. But HIV cure trials can be risky, their success is as of yet unlikely, and the medical gain of being cured is limited against a baseline of ART access. The medical (...) prospect associated with participation in cure research thus look poor. Are the risks and burdens that HIV cure research places on participants so high that it is unethical, at present, to conduct it? In this paper, I answer ‘no’. I start my argument by describing a foundational way of thinking about the ethical justification for regulatory limits on research risk; I then apply this way of thinking to HIV cure trials. In offering this analysis, I confine my attention to studies enrolling competent adults and I also do not consider risks research may pose to third parties or society. Rather, my concern is to engage with the thought that some trials are so risky that performing them is an ethically unacceptable way to treat the participants themselves. I reject this thought and instead argue that there is no level of risk, no matter how high, that inherently mistreats a participant. (shrink)

One of the fundamental ethical concerns about biomedical research is that it frequently exposes participants to risks for the benefit of others. To protect participants’ rights and interests in this context, research regulations and guidelines set out a mix of substantive and procedural requirements for research involving humans. Risk thresholds play an important role in formulating both types of requirements. First, risk thresholds serve to set upper risk limits in certain types of research. Second, risk thresholds serve to demarcate risk (...) categories that streamline risk-adapted systems of ethical oversight. But although risk thresholds play such an important role in research governance, there is a need both to better define the existing risk thresholds and to delineate new thresholds in order to develop more risk-adapted systems of research oversight. The present paper examines the existing minimal risk threshold and the surrounding debates with the goal of deriving a systematic approach to setting thresholds of research risk. (shrink)

Risk–benefit assessment is a routine requirement for research ethics committees that review and oversee biomedical research with human subjects. Nevertheless, it remains unclear how to weigh and balance risks to research participants against the social benefits that flow from generating biomedical knowledge. In this article, we address the question of whether there are any reasonable criteria for defining the limit of permissible risks to individuals who provide informed consent for research participation. We argue against any a priori limit to permissible (...) research risks. However, attention to the uncertainty of potential social benefit that can be derived from any particular study warrants caution in exposing prospective research participants to a substantial likelihood of serious harm. (shrink)

Some form of agent-relative constraint against the killing of innocent personsis a central principle in deontological moraltheories. In this article I make two claimsabout this constraint. First, I argue that somekillings of innocents performed incircumstances usually not taken to exculpatethe killer are not even pro tanto wrong.Second, I contend that either there is noagent-relative constraint against the killingof innocents or this constraint has a verydifferent shape from that which deontologistsnormally take it to have. My defence of theseclaims rests on two (...) propositions. First, inkilling someone one may actually prolong thatperson''s life. Roughly, life-prolongingkillings are possible, because to kill someoneis to perform an act that causes someone''sdeath and it might well be true that, had onenot performed this act, one''s ``victim'''' wouldhave died earlier. Second, all other thingsbeing equal, killing and causing a person to beunconscious are morally equivalent. Both ofthese propositions are defended in thearticle. (shrink)

Cover -- Half Title -- Title -- Copyright -- Dedication -- Contents -- Acknowledgments -- 1 Preliminaries -- 1.1 What Normative Ethics Is -- 1.2 What Normative Ethics Is Not -- 1.3 Defending Normative Theories -- 1.4 Factors and Foundations -- PART I FACTORS -- 2 The Good -- 2.1 Promoting the Good -- 2.2 Well-Being -- 2.3 The Total View -- 2.4 Equality -- 2.5 Culpability, Fairness, and Desert -- 2.6 Consequentialism -- 3 Doing Harm -- 3.1 Deontology -- (...) 3.2 Thresholds -- 3.3 The Scope of the Constraint -- 3.4 Doing and Allowing -- 3.5 Intending Harm -- 4 Other Constraints -- 4.1 Lying -- 4.2 Promises -- 4.3 Special Obligations -- 4.4 Conventions -- 4.5 Duties to Oneself -- 5 Further Factors -- 5.1 Demanding Too Much -- 5.2 Options -- 5.3 Rights -- 5.4 Interaction -- PART 2 FOUNDATIONS -- 6 Teleological Foundations -- 6.1 Foundational Theories -- 6.2 Egoism -- 6.3 Virtues -- 6.4 Act Consequentialism -- 6.5 Rules -- 7 Deontological Foundations -- 7.1 Contractarianism -- 7.2 Universalizability -- 7.3 The Ideal Observer -- 7.4 Reflection -- 7.5 Foundational Pluralism -- 7.6 Possibilities -- Suggested Readings -- References -- About the Book and Author -- Index. (shrink)

Institutional review boards (IRBs) have a reputation for impeding research. This reputation is understandable inasmuch as many studies are poorly designed, exploit participants, or do not ask a relevant question , and it is entirely proper that IRBs should reject such proposals. However, IRBs also frequently reject or tamper with perfectly sound and relevant studies in the name of protecting participants from harm, in accordance with the widely accepted message that “clinical research is justified only when participants are protected from (...) excessive risks”. Here, I argue that IRBs should never reject a study because it poses too high a risk to participants, and that their role should be confined to ensuring that risks and any potential benefits are fully explained to potential participants. Everyone should have the right to participate in research without paternalistic decisions about risk being made on their behalf. (shrink)

From the apathetic reaction to atrocities committed in Vietnam by the United States and its allies, one may conclude that moral restrictions on the conduct of war command almost as little sympathy among the general public as they do among those charged with the formation of U.S. military policy. Even when restrictions on the conduct of warfare are defended, it is usually on legal grounds alone: their moral basis is often poorly understood. I wish to argue that certain restrictions are (...) neither arbitrary nor merely conventional, and that their validity does not depend simply on their usefulness. There is, in other words, a moral basis for the rules of war, even though the conventions now officially in force are far from giving it perfect expression. (shrink)

Eyal et al have recently argued that researchers should consider conducting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human challenge studies to hasten vaccine development. We have conducted (J. L.) and overseen (L. D.) human challenge studies and agree that they can be useful in developing anti-infective agents. We also agree that adults can autonomously choose to undergo risks with no prospect of direct benefit to themselves. However, we disagree that SARS-CoV-2 challenge studies are ethically appropriate at this time, for (...) 3 reasons: (1) current scientific knowledge of SARS-CoV-2 infection is insufficient to manage risks; (2) autonomous decision making, while necessary, does not override concerns about risk; and (3) undertaking challenge studies now would imperil confidence in the research enterprise, potentially undermining the global response to the coronavirus disease 2019 (COVID-19) pandemic. (shrink)