Future pandemics and the urge to 'do something'.

Research with enhanced potential pandemic pathogens (ePPP) makes pathogens substantially more lethal, communicable, immunosuppressive or otherwise capable of triggering a pandemic. We briefly relay an existing argument that the benefits of ePPP research do not outweigh its risks and then consider why proponents of these arguments continue to confidently endorse them. We argue that these endorsements may well be the product of common cognitive biases-in which case they would provide no challenge to the argument against ePPP research. If the case against ePPP research is strong, the views of professional experts do little to move the needle in favour of ePPP research.

Willingness to trade-off years of life for an HIV cure - an experimental exploration of affective forecasting.

BACKGROUND: In the US, 1.2 million people live with HIV (PWH). Despite having near-normal life expectancies due to antiretroviral therapy (ART), many PWH seek an HIV cure, even if it means risking their lives. This willingness to take risks for a cure raises questions about "affective forecasting biases," where people tend to overestimate the positive impact of future events on their well-being. We conducted a study to test two interventions to mitigate affective forecasting in the decisions of PWH about taking HIV cure medication. METHODS: We recruited PWH to complete a 30-minute survey about their current quality of life (QoL) and the QoL they anticipate after being cured of HIV, and assigned them to either no additional intervention, to one of two interventions intended to reduce affective forecasting bias, or to both interventions: (1) a defocusing intervention designed to broaden the number of life domains people consider when imagining life changes associated with new circumstances (e.g. HIV cure); and (2) an adaptation intervention to help them gauge fading of strong emotions over time. The study design included a 2 × 2 design: defocusing (yes/no) x adaptation (yes/no) intervention. We assessed PWH's willingness to take hypothetical HIV sterilizing cure medication using the Time Trade-Off (TTO) and their quality of life predictions with WHOQOL-HIV. RESULTS: 296 PWH participated. Counter to what we had hypothesized, neither intervention significantly reduced PWH's willingness to trade time for a cure. Instead, the defocusing intervention increased their willingness to trade time (IRR 1.77, p = 0.03). Exploratory analysis revealed that PWH with lower current quality of life who received the defocusing intervention were more willing to trade time for a cure. CONCLUSION: These negative findings suggest that either these biases are difficult to overcome in the settings of HIV curative medication or other factors beyond affective forecasting biases influence willingness to participate in HIV curative studies, such as respondents' current quality of life.

The phantasm of zero suicide.

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.

Ethical and legal race-responsive vaccine allocation.

In many countries, the COVID-19 pandemic varied starkly between different racial and ethnic groups. Before vaccines were approved, some considered assigning priority access to worse-hit racial groups. That debate can inform rationing in future pandemics and in some of the many areas outside COVID-19 that admit of racial health disparities. However, concerns were raised that "race-responsive" prioritizations would be ruled unlawful for allegedly constituting wrongful discrimination. This legal argument relies on an understanding of discrimination law as demanding color-blindness. We argue that a, color-blind understanding of discrimination would be hostile only to one of two rationales for prioritizing the relevant racial minorities in settings of racial health disparities. We also propose a method for incorporating appropriate race-responsive concerns that is in many ways ethically and legally superior to ones suggested thus far. That method turns artificial intelligence, thanks precisely to its artificial and "black box" nature (features that underlie recent concerns about artificial intelligence's discriminatory potential), into an instrument of social justice.

When offering a patient beneficial treatment undermines public health.

Sometimes, offering someone beneficial care is likely to thwart the similar or more serious medical needs of more people. For example, when acute shortage is strongly predicted to persist, providing the long period on scarce intensive care that a certain COVID-19 patient needs is sometimes projected to block several future COVID-19 patients from receiving the shorter periods on intensive care that they will need. Expected utility is typically higher if the former is denied intensive care. A tempting initial account of such cases is that consequentialism supports denying care to that patient and nonconsequentialism supports providing that care. This paper argues that the consequentialist case is more complicated than it may initially seem and that nonconsequentialism sides more readily with denial of the beneficial treatment. It also shows that when denying it would directly enhance public health by a lot, either ethical approach would normally recommend denying it. Practical implications are discussed, including how to address conscientious objection to this shared recommendation.

The Ethics of Human Challenge Trials Using Emerging Severe Acute Respiratory Syndrome 2 Variants.

The world's first coronavirus disease 2019 human challenge trial using the D614G strain of severe acute respiratory syndrome 2 (SARS-CoV-2) is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta and Delta variant for a follow-up human challenge trial, and researchers at hVIVO are considering conducting these trials. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. We explore 2 specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical.

Coronavirus Disease 2019 (COVID-19) Vaccine Prioritization in Low- and Middle-Income Countries May Justifiably Depart From High-Income Countries' Age Priorities.

In high-income countries that were first to roll out coronavirus disease 2019 (COVID-19) vaccines, older adults have thus far usually been prioritized for these vaccines over younger adults. Age-based priority primarily resulted from interpreting evidence available at the time, which indicated that vaccinating the elderly first would minimize COVID-19 deaths and hospitalizations. The World Health Organization counsels a similar approach for all countries. This paper argues that some low- and middle-income countries that are short of COVID-19 vaccine doses might be justified in revising this approach and instead prioritizing certain younger persons when allocating current vaccines or future variant-specific vaccines.

Pandemic vaccine testing: Combining conventional and challenge studies.

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.

Research ethics and public trust in vaccines: the case of COVID-19 challenge trials.

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.

Do coronavirus vaccine challenge trials have a distinctive generalisability problem?

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.

How to Test Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines Ethically Even After One Is Available.

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.

Electronic Adherence Monitoring May Facilitate Intentional HIV Status Disclosure Among People Living with HIV in Rural Southwestern Uganda.

HIV status disclosure remains one of the major challenges to effective HIV prevention. Given the complexities and low rates of disclosure, new innovative strategies are needed. Since electronic adherence monitoring (EAM) are unique mobile devices that light up when transmitting data, those who see them often want to know more about them, which can potentially result in HIV status disclosure. We conducted a qualitative study to explore patient experiences with EAM for antiretroviral therapy (ART) in Uganda with a goal of understanding potential ethical concerns, including disclosure. Unexpectedly, several participants reported intentionally using EAM to facilitate HIV status disclosure to others in order to get social support, encourage HIV testing, and create awareness about HIV. Although researchers and clinicians need to be mindful of the potential for unintended HIV status disclosure through the use of EAM, they should also recognize the potential of this approach to support intended disclosure.

Rescuing Vapers Versus Rescuing Smokers: The Ethics.

Suppose for the sake of argument that wide access to electronic cigarettes would help a great many smokers quit and others avoid smoking, with a dramatic cumulative effect on population health. But suppose also that nowadays, teenagers rarely benefit from that effect, because most do not smoke and are not expected to smoke as adults. Many teenagers do vape. When the net effect of vaping on general public health is expected to remain very positive, should we nevertheless fight vaping, so as to protect teenagers from the direct risks of vaping? For example, what to do if and when certain targeted regulations that would protect teenagers would also, by making it harder to vape, substantially increase smoking in the general population? This situation may be common, and, by pitting the health interests of the general population against those of teenagers, poses an ethical dilemma. This article argues philosophically that if such tradeoffs between the health interests of adolescents and those of the general population exist, morally it is both permissible and preferable to promote the health of the general population. IMPLICATIONS: In the debate about electronic-cigarette based tobacco harm reduction, some disagreements are factual, for example, disagreements about how harmful vaping is to human lungs, and how much the option of vaping helps smokers quit. However, there is also an ethical debate: if tradeoffs between the health interests of adolescents at risk of vaping and those of the general population (driven by those of smokers) exist, who should be prioritized? This article argues that morally it is sometimes, at least, both permissible and preferable to promote the health of the general population over those of adolescents at risk of vaping.

COVID-19 controlled human infection studies: worries about local community impact and demands for local engagement.

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 Studies to Accelerate Coronavirus Vaccine Licensure.

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.

On Knowingly Setting Unrealistic Goals in Public Health.

What is the ethics of setting unrealistic goals in public health-declared goals of population health campaigns that, when introduced, are already known to be impossible to accomplish? Over the past 2 decades, major public health campaigns have set unrealistic goals, such as "eliminating" or reaching "zero" on diseases and risk factors that are clearly ineliminable.We argue that unrealistic goals can sometimes motivate action, attract funding, and help educate the public and public health practitioners better than realistic goals. Although unrealistic goal setting faces ethical challenges, including the charge of deceit and that of undermining the field's credibility, we argue that these challenges can be met.The advantages of unrealistic goal setting while overcoming these challenges can be accomplished in 2 stages: (1) an initial declaration of the attractive but unrealistic goal educates and motivates; (2) realistic, precise, and actionable subgoals then expose its unrealistic nature and preempt ongoing deceit.

Correction to: Ugandan Study Participants Experience Electronic Monitoring of Antiretroviral Therapy Adherence as Welcomed Pressure to Adhere.

The original version of this article unfortunately contained an error. The authors would like to correct the error with this erratum.

"Cure" Versus "Clinical Remission": The Impact of a Medication Description on the Willingness of People Living with HIV to Take a Medication.

Many people living with HIV (PLWHIV) state that they would be willing to take significant risks to be "cured" of the virus. However, how they interpret the word "cure" in this context is not clear. We used a randomized survey to examine whether PLWHIV had a different willingness to take a hypothetical HIV medication if it causes flu-like symptoms, but provides: (a) cure, (b) remission that was labeled "cure", or (c) remission. PLWHIV (n = 454) were more willing to take a medication that provided a "cure" versus a "remission" if the side effects lasted less than 1 year. PLWHIV were more willing to take a medication that provided a remission that was labeled "cure" versus a "remission" (p = 0.01) if the side effects lasted 2 weeks. Clinicians and researchers should be aware of the impact of the word "cure" and ensure that PLWHIV fully understand the possible outcomes of their treatment options.

Why continuing uncertainties are no reason to postpone challenge trials for coronavirus vaccines.

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.

Study bystanders and ethical treatment of study participants-A proof of concept.

The ethics of research on human subjects is often construed as a fine balance between the interests of patients in need of novel health interventions, and those of study participants who should remain safe in the process. But there is a third group in the mix. Some people belong to neither category, yet research can affect or jeopardize them. Call such people "bystanders." This article shows that thinking about bystander protection can question whether there is an upper limit on the risks that studies may legitimately visit upon their participants. Thus, thinking about appropriate bystander protection can shed light on the appropriate protection of study participants. Core research ethics, which focuses on the latter, must consider the former as well.