Self-Administration of Aspirin After Chest Pain for the Prevention of Premature Cardiovascular Mortality in the United States: A Population-Based Analysis.

BACKGROUND: Aspirin, an effective, low-cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self-administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use. METHODS AND RESULTS: We developed a population simulation model to determine the impact of self-administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643-14 574) deaths annually, after accounting for deaths due to bleeding (963; 926-1003). This translated to an estimated 166 309 YOLS (149391-185 505) at the cost of $643 235 (633 944-653 010) per year, leading to a cost-effectiveness ratio of $3.70 (3.32-4.12) per YOLS. CONCLUSIONS: For <$4 per YOLS, self-administration of aspirin within 4 hours of severe chest pain onset has the potential to save 13 000 lives per year in the US population. Benefits of reducing deaths post-AMI outweighed the risk of bleeding deaths from aspirin 10 times over.

Consent Requirements for Testing Health Policies: An Intercontinental Comparison of Expert Opinions.

Individual informed consent is a central requirement for clinical research on human subjects, yet whether and how consent requirements should apply to health policy experiments (HPEs) remains unclear. HPEs test and evaluate public health policies prior to implementation. We interviewed 58 health experts in Tanzania, Bangladesh and Germany on informed consent requirements for HPEs. Health experts across all countries favored a strong evidence base, prior information to the affected populations, and individual consent for 'risky' HPEs. Differences pertained to individual risk perception, how and when consent by group representatives should be obtained and whether HPEs could be treated as health policies. The study adds to representative consent options for HPEs, yet shows that more research is needed in this field - particularly in the present Covid-19 pandemic which has highlighted the need for HPEs nationally and globally.

Social network-based ethical analysis of COVID-19 vaccine supply policy in three Central Asian countries.

BACKGROUND: In the pandemic time, many low- and middle-income countries are experiencing restricted access to COVID-19 vaccines. Access to imported vaccines or ways to produce them locally became the principal source of hope for these countries. But developing a strategy for success in obtaining and allocating vaccines was not easy task. The governments in those countries have faced the difficult decision whether to accept or reject offers of vaccine diplomacy, weighing the price and availability of COVID-19 vaccines against the concerns over their efficacy and safety. We aimed to analyze public opinion regarding the governmental strategies to obtain COVID-19 vaccines in three Central Asian countries, focusing particularly on possible ethical issues. METHODS: We searched for opinions expressed either in Russian or in the respective national languages. We provided data on the debate within three countries, drawn from social media postings and other sources. The opinion data was not restricted by source and time. This allowed collecting a wide range of possible opinions that could be expressed regarding COVID-19 vaccine supply and human participation in the vaccine trial. We recognized ethical issues and possible questions concerning different ethical frameworks. We also considered scientific data and other information, in the process of reasoning. RESULTS: As a result, public views on their respective government policies on COVID-19 vaccine supply ranged from strongly negative to slightly positive. We extracted the most important issues from public debates, for our analysis. The first issue involved trade-offs between quantity, speed, price, freedom, efficacy, and safety in the vaccines. The second set of issues arose in connection with the request to site a randomized trial in one of the countries (Uzbekistan). After considering additional evidence, we weighed individual and public risks against the benefits to make specific judgements concerning every issue. CONCLUSIONS: We believe that our analysis would be a helpful example of solving ethical issues that can arise concerning COVID-19 vaccine supply around the world. The public view can be highly critical, helping to spot such issues. An ignoring this view can lead to major problems, which in turn, can become a serious obstacle for the vaccine coverage and epidemics' control in the countries and regions.

Social network-based ethical analysis of COVID-19 vaccine supply policy in three Central Asian countries.

Background In the pandemic time, many low- and middle-income countries are experiencing restricted access to COVID-19 vaccines. An access to imported vaccines or ways to produce them locally becomes the principal source of hope. But developing a strategy for success in obtaining and allocating vaccines is not easy task. The governments in those countries have faced difficult decision whether to accept or reject offers of vaccine diplomacy, weighing price and availability of COVID-19 vaccines against concerns over their efficacy and safety. Our aim was to analyze public opinion regarding the governmental strategies to obtain COVID-19 vaccines in three Central Asian countries, focusing particularly on possible ethical issues. Methods We searched opinions expressed either in Russian or in the respective national languages. We provided data of the debate within three countries, drawn from social media postings and other sources. The opinion data was not restricted by source and time. This allowed to collect a wide range of possible opinions that could be expressed regarding COVID-19 vaccine supply and public's participation in vaccine trials. We recognized ethical issues and possible questions concerning different ethical frameworks. We also considered additional information or scientific data, in the process of reasoning. Results As a result, public views on their respective government policies on COVID-19 vaccine supply ranged from strongly negative to slightly positive. We extracted most important issues from public debates, for our analysis. The first issue involved trade-offs between quantity, speed, price, freedom, efficacy and safety in the vaccines. The second set of issues arouse in connection with the request to site a randomized trial in one of countries (Uzbekistan). After considering additional evidences, we weighed individual with public risks and benefits to make specific judgements concerning every issue. Conclusions We believe that our analysis would be a helpful example of solving ethical issues that can rise concerning COVID-19 vaccine supply round the world. The public view can be highly critical, helping to spot such issues. An ignoring this view can lead to major problems, which in turn, can become a serious obstacle for the vaccine coverage and epidemics' control in the countries and regions.

"Thought provoking", "interactive", and "more like a peer talk": Testing the deliberative interview style in Germany.

Proponents of the newly-developed "deliberative interview" argue that examining complex issues requires more dynamic and engaging interview exchanges. Unlike traditional qualitative interviews, deliberative interviewing champions opinion sharing, active debates and similar speaking times by both sides throughout the interview. Drawing on 20 interviews with health experts in Germany, we examined the process and outcome of deliberative versus conventional interviews on the topic of informed consent. The deliberative interview expedited clarity on the issue, led to more nuanced discussion and generated more knowledge overall, but was challenging because it broke the mold for traditional interviewing. Alignment in terms of gender, age, personality and professional background facilitated rapport, regardless of interview style. To manage expectations, we recommend a thorough, perhaps video-based explanation of the deliberative style prior to the interview. Deliberative interviews can bolster knowledge generation for complex issues and can be applied in public health and beyond.

Bystanders and ethical review of research: Proceed with caution.

Scientists seeking to conduct research with human subjects must first submit their proposals to research ethics committees (Institutional Review Boards [IRBs], in the United States). Some of these studies pose risks to "bystanders," i.e., people who may be affected by the research but who are not enrolled as study subjects. Should IRBs expand their scope to include oversight over possible harms to bystanders as well as research subjects? This paper presents arguments against this step. Prior review of research with human subjects, despite its evident burden on the research enterprise, is a necessary caution, because the tension between the objectives of humane treatment of research subjects and sound scientific design and procedure has in the past led to serious abuses. This rationale is inapplicable in the case of bystanders. Moreover, in view of the many and varied effects of both research practices and scientific advances on the broader public over time, those who may be considered to be "bystanders" may potentially expand without limit; requiring IRBs to anticipate these distant and long-term effects as part of prior ethical review could greatly increase its burden and its deterrent effect on research. While conducting research without concern for serious potential harm to bystanders may be irresponsible and unethical, expanding the scope of prior review by IRBs to include risks to bystanders is not required by the principles governing human subjects research, and the costs and burdens of this expansion may outweigh any expected gains.

From Doxastic to Epistemic: A Typology and Critique of Qualitative Interview Styles.

Qualitative interview styles have been guided by precedent within academic disciplines. The nature of information sought, and the role of interviewer and interviewee are key determinants across styles, which range from doxastic (focused on understanding interviewees' experiences or behaviors) to epistemic (focused on co-constructing knowledge). In this article, we position common interview styles along a doxastic-epistemic continuum, and according to the role of the interviewee (from respondent to equal partner). Through our typology and critique of interview styles, we enhance epistemic interviewing by introducing "deliberative interviews," which are more debate oriented and closer to equality in the interviewee and interviewer relationship than existing interview styles. Deliberative interviews require a comprehensive, pre-interview briefing on the subject matter followed by interactive deliberation wherein complex issues are debated across viewpoints in an effort to devise solutions. The effectiveness of this interview style in generating new knowledge warrants empirical testing across academic disciplines.

Ethical complexities of responding to bystander risk in HIV prevention trials.

Till Bärnighausen points out the medical risks that two categories of contemporary HIV prevention trials, for "treatment-as-prevention" and for "pre-exposure prophylaxis," pose to people who are not study participants. Bärnighausen's compelling case forces reconsideration of the absence of bystanders in the law governing ethical review of health research. It raises the intriguing question: to what legal protection are bystanders morally entitled? The remedy might seem to be to accord bystanders the rights and protections currently accorded to human study participants. We counsel against that remedy on three grounds, inviting colleagues to suggest alternatives.

Making Fair Choices on the Path to Universal Health Coverage: Applying Principles to Difficult Cases.

Abstract-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.

Must research benefit human subjects if it is to be permissible?

Must medical experiments with human subjects offer them a 'favourable risk-benefit ratio', that is, more expectation of benefit than harm or burden, if they are to be judged as ethically justified? Ethical justification is easier for experiments that do offer net benefit to subjects, but ethical justification is possible also for some experiments that do not. Basic science experiments with healthy volunteers and 'Phase I' drug trials that seek to determine tolerable dosage levels are routinely approved by ethical review committees; moreover, guidance they receive from government funding agencies specifically asks them to weigh risks to subjects against benefits to subjects and also benefits to those who may benefit from the knowledge gained in the experiment. If a puzzle remains, it is why there remains any assumption that research ethics requires a 'favourable risk-benefit ratio' for the individual research subject.

Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment.

Moral judgments are produced through the coordinated interaction of multiple neural systems, each of which relies on a characteristic set of neurotransmitters. Genes that produce or regulate these neurotransmitters may have distinctive influences on moral judgment. Two studies examined potential genetic influences on moral judgment using dilemmas that reliably elicit competing automatic and controlled responses, generated by dissociable neural systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate genes and identified a nominal association between a polymorphism (rs237889) of the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian moral judgment (that is, judgments favoring individual rights vs the greater good). An association was likewise observed for rs1042615 of the arginine vasopressin receptor gene (AVPR1A). Study 2 (N = 322) aimed to replicate these findings using the aforementioned dilemmas as well as a new set of structurally similar medical dilemmas. Study 2 failed to replicate the association with AVPR1A, but replicated the OXTR finding using both the original and new dilemmas. Together, these findings suggest that moral judgment is influenced by variation in the oxytocin receptor gene and, more generally, that single genetic polymorphisms can have a detectable effect on complex decision processes.

Three Case Studies in Making Fair Choices on the Path to Universal Health Coverage.

The goal of achieving Universal Health Coverage (UHC) can generally be realized only in stages. Moreover, resource, capacity, and political constraints mean governments often face difficult trade-offs on the path to UHC. In a 2014 report, Making fair choices on the path to UHC, the WHO Consultative Group on Equity and Universal Health Coverage articulated principles for making such trade-offs in an equitable manner. We present three case studies which illustrate how these principles can guide practical decision-making. These case studies show how progressive realization of the right to health can be effectively guided by priority-setting principles, including generating the greatest total health gain, priority for those who are worse off in a number of dimensions (including health, access to health services, and social and economic status), and financial risk protection. They also demonstrate the value of a fair and accountable process of priority setting.

Ethical challenges in long-term funding for HIV/AIDS.

The global response to the AIDS pandemic aims for universal access to treatment and for pursuing every possible avenue to prevention. Skeptics, doubting that the huge increases in current funding levels needed for universal treatment will ever happen, would scale back antiretroviral treatment in favor of more cost-effective preventive interventions. Economics, politics, and science figure in this debate. But there is also a question of ethical principle: Is there a moral imperative to emphasize treatment, even if emphasizing prevention would save more lives? The authors examine moral arguments that address this question, and come down on the side of saving the most lives via prevention.