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Despite their clearly demonstrated safety and effectiveness, approved vaccines against COVID-19 are commonly mistrusted. Nations should find and implement effective ways to boost vaccine confidence. But the implications for ethical vaccine development are less straightforward than some have assumed. Opponents of COVID-19 vaccine challenge trials, in particular, made speculative or empirically implausible warnings on this matter, some of which, if applied consistently, would have ruled out most COVID-19 vaccine trials and many non-pharmaceutical responses.

Notwithstanding the success of conventional field trials for vaccines against COVID-19, human challenge trials (HCTs) that could obtain more information about these and about other vaccines and further strategies against it are about to start in the UK. One critique of COVID-19 HCTs is their distinct paucity of information on crucial population groups. For safety reasons, these HCTs will exclude candidate participants of advanced age or with comorbidities that worsen COVID-19, yet a vaccine should (perhaps especially) protect such populations. We turn this cliché on its head. The truth is that either an HCT or a field trial has intrinsic generalisability limitations, that an HCT can expedite protection of high-risk participants even without challenging them with the virus, and that an important route to obtaining results generalisable to high-risk groups under either strategy is facilitated by HCTs.

In spring, summer and autumn 2020, one abiding argument against controlled human infection (CHI) studies of SARS-CoV-2 vaccines has been their impact on local communities. Leading scientists and bioethicists expressed concern about undue usage of local residents’ direly needed scarce resources at a time of great need and even about their unintended infection. They recommended either avoiding CHI trials or engaging local communities before conducting any CHIs. Similar recommendations were not made for the alternative—standard phase III field trials of these same vaccines. We argue that the health effects of CHI studies on local residents not participating in the study tend to be smaller and more positive than those of field trials. That is all the more so now that tested vaccines are being rolled out. Whether or not local community engagement is necessary for urgent vaccine studies in the pandemic, the case for its engagement is stronger prior to field trials than prior to CHI studies.

Human challenge trials to test the efficacy of vaccine candidates against SARS‐CoV‐2, the novel coronavirus behind Covid‐19, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid‐19 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.

To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection (or ‘challenge’) trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.

Despite doing well on antiretroviral therapy, many people living with HIV have expressed a willingness to accept substantial risks for an HIV cure. To date, few studies have assessed the specific quantitative maximal risk that future participants might take; probed whether, according to future participants, the risk can be offset by the benefits; and examined whether taking substantial risk is a reasonable decision. In this qualitative study, we interviewed 22 people living with HIV and used standard gamble methodology to assess the maximum chance of death a person would risk for an HIV cure. We probed participants’ reasoning behind their risk‐taking responses. Conventional inductive content analysis was used to categorize key themes regarding decision‐making. We found that some people would be willing to risk even death for an HIV cure, and some of their reasons were plausible and went far beyond the health‐related utility of an HIV cure. We contend that people's expressed willingness to take substantial risk for an HIV cure should not be dismissed out of hand.

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured.

AbstractAbstract—Progress toward universal health coverage (UHC) requires making difficult trade-offs. In this journal, Dr. Margaret Chan, the World Health Organization (WHO) Director-General, has endorsed the principles for making such decisions put forward by the WHO Consultative Group on Equity and UHC. These principles include maximizing population health, priority for the worse off, and shielding people from health-related financial risks. But how should one apply these principles in particular cases, and how should one adjudicate between them when their demands conflict? This article by some members of the Consultative Group and a diverse group of health policy professionals addresses these questions. It considers three stylized versions of actual policy dilemmas. Each of these cases pertains to one of the three key dimensions of progress toward UHC: which services to cover first, which populations to prioritize for coverage, and how to move from out-of-pocket expenditures to prepayment with pooling of funds. Our cases are simplified to highlight common trade-offs. Though we make specific recommendations, our primary aim is to demonstrate both the form and substance of the reasoning involved in striking a fair balance between competing interests on the road to UHC.

This article lays out a wide spectrum of candidate ethical solutions for the challenge on which this JMEsymposium 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.

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.

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.

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

A recent measles outbreak in the United States was linked to a single source, yet it spanned eighteen jurisdictions and infected 121 people.1Forty-seven states currently allow legal exemption from vaccination on religious grounds, eighteen of which also allow it on philosophical grounds.2Recent 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.3We 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.

Many studies that seek to cure HIV must ask participants to interrupt their antiretroviral treatment. In such circumstances, is it permissible to include a placebo group in the study? We explain why doing so is a scientific and an ethical necessity, and more benign than imagined.

When a group of doctors and nurses from Boston, Massachusetts, provided evaluation and heart surgery to children in Ghana, they encountered three rationing dilemmas: (1) What portion of surgery slots should they reserve for the simplest, most cost-effective surgeries? (2) How much time should be reserved for especially simple, nonsurgical interventions? (3) How much time should be reserved to training local staff to perform such surgeries? This article investigates these three dilemmas.

Both left libertarians, who support the redistribution of income and wealth through taxation, and right libertarians, who oppose redistributive taxation, share an important view: that, looming catastrophes aside, the state must never redistribute any part of our body or our person without our consent. C?cile Fabre rejects that view. For her, just as the undeservedly poor have a just claim to money from their fellow citizens in order to lead a minimally flourishing life (here Fabre sides with left libertarians), the undeservedly ?medically poor? have a just claim to help from fellow citizens in order to lead such a life. Such obligatory help may in principle involve even the supply of body parts for transplantation. The state ought to exact such resources from the medically rich whenever doing so would secure the prospect of a minimally flourishing life to the medically poor without denying that prospect to anyone else. Fabre criticizes Ronald Dworkin's belief in ?a prophylactic line that comes close to making the body inviolate, that is, making body parts not parts of social resources at all?. For her, ?Duties to help .?.?. do not stop at material resources: they involve the body .?.?. in invasive ways? (p. 119).

This response to Gail Henderson et alargues that they were right that interviewees’ appraisals of cure study participation should inform (future) protocol review decisions, but wrong to take these appraisals at face value.

This is an afterword to the JMEsymposium on the benefit/risk ratio challenge in clinical research, and the case of HIV cure. It notes implications of the symposium for research ethics in general.

This piece introduces the JME symposium ‘The benefit/risk ratio challenge in clinical research, and the case of HIV cure.’

ObjectiveTo determine, in one low income country (Nepal), which characteristics of medical students are associated with graduate doctors staying to practise in the country or in its rural areas.DesignObservational cohort study.SettingMedical college registry, with internet, phone, and personal follow-up of graduates.Participants710 graduate doctors from the first 22 classes (1983-2004) of Nepal’s first medical college, the Institute of Medicine.Main outcome measuresCareer practice location (foreign or in Nepal; in or outside of the capital city Kathmandu) compared with certain pre-graduation characteristics of medical student.Results710 (97.7%) of the 727 graduates were located: 193 (27.2%) were working in Nepal in districts outside the capital city Kathmandu, 261 (36.8%) were working in Kathmandu, and 256 (36.1%) were working in foreign countries. Of 256 working abroad, 188 (73%) were in the United States. Students from later graduating classes were more likely to be working in foreign countries. Those with pre-medical education as paramedics were twice as likely to be working in Nepal and 3.5 times as likely to be in rural Nepal, compared with students with a college science background. Students who were academically in the lower third of their medical school class were twice as likely to be working in rural Nepal as those from the upper third. In a regression analysis adjusting for all variables, paramedical background (odds ratio 4.4, 95% confidence interval 1.7 to 11.6) was independently associated with a doctor remaining in Nepal. Rural birthplace (odds ratio 3.8, 1.3 to 11.5) and older age at matriculation (1.1, 1.0 to 1.2) were each independently associated with a doctor working in rural Nepal.ConclusionsA cluster of medical students’ characteristics, including paramedical background, rural birthplace, and lower academic rank, was associated with a doctor remaining in Nepal and with working outside the capital city of Kathmandu. Policy makers in medical education who are committed to producing doctors for underserved areas of their country could use this evidence to revise their entrance criteria for medical school.

Under what I call ”Near-Universal Basic Income,” or NUBI, everyone receives a high level of basic income, except for the rich. NUBI is therefore only near-universal and it requires means-testing. It is an economic hybrid: a cross between Universal Basic Income (UBI) and conservative social relief. My thesis is that if standard considerations that are often advanced to support UBI against social relief are successful, then these combined considerations probably lend NUBI even greater support. Thus, UBI supporters should consider becoming NUBI supporters. The considerations I examine focus on (1) sufficiency; (2) cost cuts; (3) equality; (4) freedom; (5) the social bases of self-respect; and (6) political resilience.

Under what I call "Near-Universal Basic Income," or NUBI, everyone receives a high level of basic income, except for the rich. NUBI is therefore only near-universal and it requires means-testing. It is an economic hybrid: a cross between Universal Basic Income (UBI) and conservative social relief. My thesis is that if standard considerations that are often advanced to support UBI against social relief are successful, then these combined considerations probably lend NUBI even greater support. Thus, UBI supporters should consider becoming NUBI supporters. The considerations I examine focus on (1) sufficiency; (2) cost cuts; (3) equality; (4) freedom; (5) the social bases of self-respect; and (6) political resilience.