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Purpose of reviewSeveral promising experimental pathways exist for long-term control of HIV in the absence of antiretroviral therapy (HIV 'remission') and are now being tested in early clinical studies. These studies can be invasive and pose a host of distinctive risks to participants, as well as to nonparticipants, especially to participants' fetuses, and sexual partners.Recent findingsEthical analyses of these studies have mainly focused on the risks to study participants. They recommend, and some investigators implement, procedures to mitigate risks for participants or to offset them with direct, indirect, and nonmedical benefits. They also suggest ways to keep participants' consent highly voluntary and informed. Rarely do ethicists propose keeping the social value of studies high. Of these recommended responses, only the latter, rarer proposals help address the risk to nonparticipants, as would some novel ways to address that risk.SummaryHIV remission studies pose a number of ethical dilemmas. Many current investigative approaches put the participant at significant risk, but well established guidelines exist for mitigating this risk. Ethical issues that are not being fully addressed include risk to nonparticipants and the need to consider the societal value of studies, for example, their prospective impact on the global HIV burden. VIDEO ABSTRACT.

Governments and non-governmental organisations are increasingly adopting a 'zero-suicide' goal, but what such a goal precisely involves is unclear. Ostensibly it strongly prioritises the prevention and elimination of all suicide. We argue that, so understood, a societal goal of zero suicide risks contravening several ethical principles. In terms of beneficence and non-maleficence, a 'zero-suicide' goal risks being inefficient and may burden or harm many people. Autonomy-wise, a blanket ban on all suicide is excessive. As regards social justice, zero suicide risks focusing on the symptoms of social malaise instead of the structures causing it. With respect to transparency, a 'zero' goal that cannot be met makes these authorities look detached and risks frustration, distrust and, worse, stigmatisation of suicide and of mental health conditions. Instead, we propose a middle path for suicide prevention, founded on harm reduction, 'soft group paternalism' and efforts directed at increased quality of life for disadvantaged groups. Although soft group paternalism respects autonomy, this approach permits coercive interferences in certain circumstances. We hope that the justificatory framework tying together these largely familiar elements is novel and sensible. [ABSTRACT FROM AUTHOR]

Early into COVID, human challenge trials were considered, but usually as alternatives to conventional randomized controlled trials. Instead, assessment of authorized COVID vaccines, of further COVID vaccines, and of vaccines against future pandemics should combine both designs, in five different ways, including a wholly novel one that we elaborate, Viz., combining data from both designs to answer a single question. [ABSTRACT FROM AUTHOR]

The article proposes paired publication as a way to address the barrier between philosophical insight and bioethics. Four models for achieving paired publications of philosophical bioethics include adapting existing interdisciplinary bioethics journals, ethics appendices in medical, public health and scientific journals, policy summaries in philosophy journals and coordinated publications in medical and philosophy journals.

A vaccine trial with a conventional challenge design can be very fast once it starts, but it requires a long prior process, in part to grow and standardize challenge virus in the laboratory. This detracts somewhat from its overall promise for accelerated efficacy testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidates, and from the ability of developing countries and small companies to conduct it. We set out to identify a challenge design that avoids this part of the long prior process. Literature in trial design (including a proof of concept flu challenge trial by B. Killingley et al.), vaccinology, medical ethics, and various aspects of COVID response. A challenge design with deliberate natural viral exposure avoids the need to grow culture. This new design is described and compared both to a conventional challenge design and to a conventional phase III field trial. In comparison, the proposed design has ethical, scientific, and feasibility strengths. The proposed new design should be considered for future vaccine trials. [ABSTRACT FROM AUTHOR]

Although vaccines against severe acute respiratory syndrome coronavirus 2 have now been found safe and efficacious, there remains an urgent global health need to test both these vaccines and additional vaccines against the same virus. Under variable conditions, either standard or unusual designs would for both familiar and often-missed reasons make continued testing possible and ethical. [ABSTRACT FROM AUTHOR]

Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care. [ABSTRACT FROM AUTHOR]

Novel monitoring technologies in HIV research, such as electronic adherence monitors (EAMs), have changed the nature of researcher-participant interactions. Yet little is known about how EAMs and the resulting interaction between researchers and participants affect research participation and the data gathered. We interviewed participants and research assistants (RAs) in an observational cohort study involving EAMs for HIV antiretroviral therapy (ART) in Uganda. We qualitatively explored interviewees' views about ethical issues surrounding EAMs and assessed data with conventional and directed content analysis. Participants valued their relationships with RAs and were preoccupied with RAs' perceptions of them. Participants were pleased when the EAM revealed regular adherence, and annoyed when it revealed non-adherence that contradicted self-reported pill-taking behavior. For many, the desire to maintain a good impression incentivized adherence. But some sought to creatively conceal non-adherence, or refused to use the EAM to avoid revealing non-adherence to RAs. These findings show that participants' perceptions of the study staff's perceptions of them affected the experience of being monitored, study participation, and ultimately the data gathered in the study. Investigators in monitoring-based research should be aware that social interactions between participants and study staff could affect both the practical and ethical conduct of that research. [ABSTRACT FROM AUTHOR]

With the expansion of antiretroviral treatment programmes, many children and adolescents with HIV in sub-Saharan Africa could expect to live healthy lives. Yet adolescents have the highest levels of poor antiretroviral adherence and of loss to follow-up compared with other age groups. This can lead to increased morbidity and mortality, to the development of drug-resistant strains, and to high societal costs. While financial incentives have been extensively used to promote medication adherence among adults, their use among adolescents remains rare. And while there is a large body of ethical literature exploring financial incentives among adults, little philosophical thought has gone into their use among adolescents. This paper explores three oft-mentioned ethical worries about financial incentives for health behaviours and it asks whether these concerns are more serious in the context of incentives for improving adolescent adherence. The three worries are that such incentives would unduly coerce adolescents' decision-making, would compromise distributive justice and would crowd out intrinsic motivations and non-monetary values. Our tentative conclusion is that more empirical investigation of these concerns is necessary, and that at this point they are not compelling enough to rule out trials in which adolescents are incentivised for antiretroviral adherence. [ABSTRACT FROM AUTHOR]

This article lays out a wide spectrum of candidate ethical solutions for the challenge on which this JME symposium focuses: the benefit:risk ratio challenge to some early-phase HIV cure and remission studies. These candidate solutions fall into four categories: ones that seek to reduce risks in early-phase HIV cure and remission studies, ones that enhance the benefits for these studies' participants (or show that those were adequate in the first place), ones that focus on participants' free and informed consent to participate and ones according to whom the large benefits to non-participants can defeat considerations about individual participant net risks. In so doing, this article also structures the rest of the symposium. [ABSTRACT FROM AUTHOR]

Electronic adherence monitors (EAMs) record and report an array of health behaviors, ranging from taking daily medications to wearing medical devices. EAMs are utilized in research worldwide and are being investigated for clinical use. However, there is also growing popular concern about the extent to which electronic devices may be used to monitor individuals, including allegations in the media that EAMs represent a move towards "Big Brother" in medicine. Here, we highlight the unique benefits as well as the potential ethical challenges that electronic adherence monitoring generates. These challenges surround autonomy, privacy and confidentiality, trust, and ancillary care obligations. We describe key questions within each of these domains that warrant further investigation, and present potential solutions to many of the concerns raised. [ABSTRACT FROM AUTHOR]

Responding to critical shortages of physicians, most sub-Saharan countries have scaled up training of non-physician clinicians (NPCs), resulting in a gradual but decisive shift to NPCs as the cornerstone of healthcare delivery. This development should unfold in parallel with strategic rethinking about the role of physicians and with innovations in physician education and in-service training. In important ways, a growing number of NPCs only renders physicians more necessary -- for example, as specialized healthcare providers and as leaders, managers, mentors, and public health administrators. Physicians in sub-Saharan Africa ought to be trained in all of these capacities. This evolution in the role of physicians may also help address known challenges to the successful integration of NPCs in the health system. [ABSTRACT FROM AUTHOR]

During the 2014-2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible-and it often will be-it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise-requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants' prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial.

The article discusses the obligation, burden or cost of ancillary care in medical and health care studies. It explains that the safety and validity of research do not always meet the medical needs of study participants. The research provision does not always respond to the study aims and objectives.

In many countries worldwide, especially in Sub-Saharan Africa, a shortage of physicians limits the provision of lifesaving interventions. One existing strategy to increase the number of physicians in areas of critical shortage is conditioning medical school scholarships on a precommitment to work in medically underserved areas later. Current practice is usually to demand only one year of service for each year of funded studies. We show the effectiveness of scholarships conditional on such precommitment for increasing physician supplies in underserved areas. Then we defend these scholarships against ethical worries that they constitute slavery contracts; rely on involuntary, biased, or unauthorized early consent by a young signatory; put excessive strains on signed commitments; give rise to domination; and raise suspicion of slavery contracts. Importantly, we find that scholarships involving far longer commitment than current practice allows would also withstand these worries. Policymakers should consider introducing conditional scholarships, including long-term versions, as a means to increasing the supply of physicians to medically underserved areas. [ABSTRACT FROM PUBLISHER]

Patients’ medical conditions can result from their own avoidable risk taking. Some lung diseases result from avoidable smoking and some traffic accidents result from victims’ reckless driving. Although in many nonmedical areas we hold people responsible for taking risks they could avoid, it is normally harsh and inappropriate to deny patients care because they risked needing it. Why? A popular account is that protecting everyone’s “decent minimum,” their basic needs, matters more than the benefits of holding people accountable. This account is deficient. Protecting the decent minimum is not always served by offering noncompliant patients either nonbasic or basic care. Nor is protecting that minimum always served by unconditional medical care better than by nonmedical interventions. To interpret the decent minimum in democratic terms is a futile response to these challenges. Ideas for new accounts are suggested. [ABSTRACT FROM PUBLISHER]

The majority of deaths due to tobacco in the twenty-first century will occur in the developing world, where over 80% of current tobacco users live. In November 2010 guidelines were adopted for implementing Article 14 of the World Health Organization’s Framework Convention on Tobacco Control (FCTC). The guidelines call on all countries to promote tobacco treatment programs. Nevertheless, some experts argue for a strict focus, at least in developing countries, on population-based measures such as taxes and indoor air laws, which they consider more cost-effective than individual treatment. In this article we defend tobacco dependence treatment in developing countries. First, these experts understate the comparative cost-effectiveness of individual treatment programs. Second, they overlook numerous ethical considerations beyond cost-effectiveness that support individual tobacco treatment in developing countries. We conclude that the strict population-based focus in developing country tobacco control advocated by some experts is misplaced. In general, developing nations should combine population-based measures and individual tobacco treatment programs. [ABSTRACT FROM PUBLISHER]

Commentators on the ethics of translational research find it morally problematic. Types of translational research are said to involve questionable benefits, special risks, additional barriers to informed consent, and severe conflicts of interest. Translational research conducted on the global poor is thought to exploit them and increase international disparities. Some commentators support especially stringent ethical review. However, such concerns are grounded only in pre-approval translational research (now called T1). Whether or not T1 has these features, translational research beyond approval (T2: phase IV, health services, and implementation research) is unlikely to and, when conducted on the global poor, may support development. Therefore, insofar as T1 is morally problematic, and no independent objections to T2 exist, the ethics of translational research is diverse: while some translational research is problematic, some is not. Funding and oversight should reflect this diversity, and T2 should be encouraged, particularly when conducted among the global poor. [ABSTRACT FROM AUTHOR]

The author offers comments on the article "Shared vulnerabilities in research," by Eric Chwang which appeared in "American Journal of Bioetics." Topics include shared vulnerability in research as difficulty providing informed consent and as elevated liability to be wronged, the vulnerability of ethnic, racial and economic minorities in being more often wronged than other people in research, and the personalization of reviewers' risk-benefit ration determinations.

The article discusses the article "Problems with Prioritization: Exploring Ethical Solutions to Inequalities in HIV Care" by Kjell Arne Johansson and Ole Norheim. In the article the authors offer their opinions on several points which are raised in Norheim and Johansson's article and on the moral and ethical issues that are faced in the allocation of resources for treating patients with HIV and AIDS.

A letter to the editor is presented in response to the article "The Diverse Ethics of Translational Research," by N. Sofaer and N. Eyal.

• 'Low-dosage' challenge studies use comparably lower doses per participant. • They have scientific, pragmatic and ethical advantages: they are faster, have safer dose escalation, are a safer challenge, and have fewer type II errors. • Low-dosage challenges are worth considering for COVID-19 challenges and future uses. The design of human challenge studies balances scientific validity, efficiency and study safety. This Perspective explores some advantages and disadvantages of 'low-dosage' challenge studies, in the setting of testing second-generation vaccines against COVID-19. Compared with a conventional vaccine challenge, a low-dosage vaccine challenge would be more likely to start, and start earlier. A low-dosage challenge would also be less likely to rule out a vaccine candidate that would have potentially been effective, particularly in certain target uses. A key ethical advantage of a low-dosage challenge over a conventional challenge is that both it and its dose escalation process are safer for each participant. Low-dosage studies would require larger numbers of participants than conventional challenges, but this and other potential disadvantages are less serious than they may initially appear. Overall, low-dosage challenges should be considered for certain roles such as prioritizing between second-generation vaccines against COVID-19. [ABSTRACT FROM AUTHOR]

Michael Bloomberg's three terms in New York City's mayoral office are coming to a close. His model of governance for public health influenced cities and governments around the world. What should we make of that model? This essay introduces a symposium in which ethicists Sarah Conly, Roger Brownsword and Alex Rajczi discuss that legacy. [ABSTRACT FROM AUTHOR]

Background: Widely expected cuts to budgets for global HIV/AIDS response force hard prioritization choices. Setting: We examine policies for antiretroviral therapy (ART) eligibility through the lens of the most relevant ethical approaches. Methods: We compare earlier ART eligibility to later ART eligibility in terms of saving the most lives, life-years, and quality-adjusted life-years, special consideration for the sickest, special consideration for those who stand to benefit the most, special consideration for recipients' own health needs, and special consideration to avoid denying ART permanently. Results: We argue that, in most low- and middle-income countries with generalized HIV/AIDS epidemic, ethically, ART for sicker patients should come before ART eligibility for healthier ones immediately on diagnosis (namely, before "universal test and treat"). In particular, reserving all ART for sicker patients would usually save more life-years, prioritize the sickest, and display other properties that some central ethical approaches find important, and that concern none—so ethically, it is "cross-theoretically dominant," as we put it. Conclusions: In most circumstances of depressed financing in low- and middle-income countries with generalized HIV/AIDS epidemic, reserving all ART for sicker patients is more ethical than the current international standard. [ABSTRACT FROM AUTHOR]

A recent measles outbreak in the United States was linked to a single source, yet it spanned eighteen jurisdictions and infected 121 people. 1 Forty-seven states currently allow legal exemption from vaccination on religious grounds, eighteen of which also allow it on philosophical grounds. 2 Recent research usually accepts a fundamental right to vaccine exemption and primarily seeks ways to protect herd immunity while also respecting that right, for example, by keeping the exemption available yet harder to procure or by imposing torts for infection-related injury. 3 We argue that when herd immunity is at risk, any moral claim to exemption from vaccination on conscientious, philosophical, or religious grounds is overridden. Our argument rests on an analogy to a series of situations in which a person puts others at risk through philosophically or religiously motivated choices. In these situations, intuitively, there is no claim-right to compromise the safety of others. Similarly, we propose, there is no claim-right to refuse vaccination, regardless of one's conscience, when refusal is sufficiently likely to seriously affect herd immunity and the safety of others. We also address several counterarguments. The lack of a claim-right to exemption when herd immunity is at risk does not mean, however, that it is always prudent for the state to force vaccination, or even that forcing vaccinations must be legal. Alternatives to forced vaccination may prove wiser and more conducive to high vaccination rates. [ABSTRACT FROM AUTHOR]