Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States

Background One of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it. Methods We conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable. Results All four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants’ comfort and needs at the EOL. Conclusion Because of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research’s impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings.

Operationalising a real-time research ethics approach: supporting ethical mindfulness in agriculture-nutrition-health research in Malawi

Background There have been notable investments in large multi-partner research programmes across the agriculture-nutrition-health (ANH) nexus. These studies often involve human participants and commonly require research ethics review. These ANH studies are complex and can raise ethical issues that need pre-field work, ethical oversight and also need an embedded process that can identify, characterise and manage ethical issues as the research work develops, as such more embedded and dynamic ethics processes are needed. This work builds on notions of ‘ethics in practice’ by developing an approach to facilitate ethical reflection within large research programmes. This study explores the application of a novel ‘real-time research ethics approach’ (RTREA) and how this can support ethical mindfulness. This involves embedding ethical analysis and decision-making within research implementation, with a continuous dialogue between participants and researchers. The aim is to improve ethical responsiveness and participant experience, which in turn may ethically support adherence and retention. In this case study, a bioethics team (BT) was embedded in a community-based randomised, controlled trial conducted in rural Malawi, titled the ‘Addressing Hidden Hunger with Agronomy’. To identify ethical issues, the researchers conducted ten focus group discussions, fourteen in-depth interviews with key informants, two workshops, observed two sensitisation and three activity meetings conducted by the trial team, and analysed fifteen reports from pre-trial to trial implementation. Results The RTREA facilitated the identification of social and ethical concerns and made researchers aware of participants’ ‘lived research experience’. To address concerns and experiences, the BT worked with researchers to facilitate conversation spaces where social and ethical issues were discussed. Conversation spaces were designed to create partnerships and promote participatory methods to capture trial participants’ (TPs) perspectives and experiences. Conclusions The use of RTREA showed the value of real-time and continuous engagement between TPs and researchers. These real-time processes could be embedded to complement traditional ethical guidance and expert opinions. A deeper engagement appeared to support greater operationalising of principles of inclusion, empowerment, and participant autonomy and supported researchers ‘ethical mindfulness’ which in turn may support instrumental outcomes of high recruitment, retention, and adherence levels.

The role of community advisory boards in community-based HIV clinical trials: a qualitative study from Tanzania

Background Community Advisory Boards (CAB) have become essential organs of involving communities in HIV clinical trials especially in developing countries. However, limited empirical evidence exists on the role of CABs in low and middle-income countries including Tanzania. This study aims at exploring the role of CABs in community-based HIV clinical trials conducted in Tanzania. Methodology We adopted a phenomenological approach to purposefully select HIV clinical trial stakeholders. These included CAB members, researchers and Institutional Review Board (IRB) members in Tanzania. We conducted In-depth Interviews (IDIs) with ten participants and three Focus Group Discussions (FGDs) with eighteen participants. The data were thematically analyzed with the aid of MAXQDA software version 20.2.1. Results The findings indicate that at every stage of implementation of a community-based HIV clinical trial, a functioning CAB is important for its success. This importance is based on contextualization of the informed consent process and protocol, managing rumours in the community, weighing trial risks and benefits, sensitizing the community, assisting participant recruitment, tracing and retention. However, being perceived as financial beneficiaries than community representatives emerged as a challenge to CAB members. Conclusion The study empirically indicates the need for functioning CABs in every stage of implementation of community-based HIV clinical trials. The roles of which are interwoven in serving research goals and protecting the interests of the community and that of trial participants.

Attitudes on euthanasia among medical students and doctors in Sri Lanka: a cross sectional study

Background Euthanasia is a topic of intense ethical debate and it is illegal in most countries at present, including Sri Lanka. The aim of this descriptive cross-sectional study of medical students and practicing doctors was to explore the acceptance of euthanasia and physician assisted suicide (PAS), and factors influencing this opinion. Methods A customised online questionnaire which explored opinions on euthanasia was administered to first and final year medical undergraduates in University of Colombo and practicing doctors with more than 5 years of work experience at The National Hospital of Sri Lanka. Attitudes on euthanasia and PAS were also assessed with the attitudes towards euthanasia (ATE) Scale, which is a 10-item questionnaire. Results A total of 425 individuals responded (males: 178, 42%, age: median – 27 years), which included 143 (33.6%) first-year medical undergraduates, 141 (33.2%) final-year medical undergraduates and 141 (33.2%) practicing doctors. More participants (200, 47.1%) favoured legalizing euthanasia than those directly opposing it (110, 25.9%), but a significant proportion (27%) remained undecided. The mean scores of ATE questionnaire from the whole sample were generally unfavourable towards euthanasia/PAS. Accepting euthanasia as an option for oneself (p = < 0.001) was the strongest predictor of favouring euthanasia/PAS or supporting its legalization. Conclusion In this cross-sectional survey, more respondents supported legalisation of euthanasia in Sri Lanka than those openly opposing it. Yet, a significant minority that responded as “undecided” for legalisation, were more likely to have unfavourable ATE.

What drives public attitudes towards moral bioenhancement and why it matters: an exploratory study

The paper represents an empirical study of public attitudes towards moral bioenhancement. Moral bioenhancement implies the improvement of moral dispositions, i.e. an increase in the moral value of the actions or character of a moral agent. The views of bioethicists and scientists on this topic are present in the ongoing debate, but not the view of the public in general. In order to bridge the gap between the philosophical debate and the view of the public, we have examined attitudes towards moral bioenhancement. The participants were people from Serbia older than 15, who voluntarily completed an online questionnaire. The questionnaire consisted of a brief introduction to moral bioenhancement, seven general questions, 25 statements about participants’ attitudes towards moral bioenhancement, and five examples of moral dilemmas. The questionnaire also included questions which were used to reveal their preference of either deontology, or utilitarianism. Participants were asked to what degree they agree or disagree with the statements. The results showed that the means used to achieve moral enhancement, the level of education, and preference for deontology or utilitarianism do have an impact on public attitudes. Using exploratory factor analysis, we isolated four factors that appear to drive the respondents' attitudes toward moral bioenhancement, we named: general—closeness, fear of change, security, and voluntariness. Each factor in relationship to other variables offers new insights that can inform policies and give us a deeper understanding of the public attitudes. We argue that looking into different facets of attitudes towards moral bioenhancement improves the debate, and expands it.

Examining study participants’ decision-making and ethics-related experiences in a dietary community randomized controlled trial in Malawi

Background The participant recruitment process is a key ethical pivot point when conducting robust research. There is a need to continuously review and improve recruitment processes in research trials and to build fair and effective partnerships between researchers and participants as an important core element in ensuring the ethical delivery of high-quality research. When participants make a fair, informed, and voluntary decision to enroll in a study, they agree to fulfill their roles. However, supporting study participants to fulfill study requirements is an important ethical obligation for researchers, yet evidenced as challenging to achieve. This paper reports on participants’ motivations to volunteer and remain part of a dietary study conducted in Kasungu District, Malawi. Methods We conducted twenty in-depth interviews (with chiefs, religious leaders, trial participants, and health surveillance assistants), five systematic ethnographic observations, and fourteen focus group discussions with trial participants and their partners. Interviews were audio-recorded and transcribed verbatim. We used a grounded theory methodology to analyse data that included coding, detailed memo writing, and data interpretation. Findings The findings reveal that many participants had concerns during the trial. Thematically, experiences included anxieties, mistrust of researchers, rumours, fears of exploitation, and misconceptions. Anonymous concerns collected from the participants were reported to the trial team which enabled the researchers to appropriately support participants. Despite initial concerns, participants described being supported and expressed motivation to take up their role. Conclusion These findings highlight a diverse map of multiple notions of what is ethically relevant and what can impact participation and retention within a study. The study has revealed how embedding a responsive approach to address participants’ concerns and ethical issues can support trust relationships. We argue for the need to employ embedded ethics strategies that enhance informed consent, focus on participants’ needs and positive experiences, and support researchers to fulfill their roles. This work highlights the need for research ethics committees to focus on the risks of undue influence and prevent exploitation especially in settings with a high asymmetry in resources and power between researcher and participant groups. Trial Registration: The Addressing Hidden Hunger with Agronomy (Malawi) trial was registered on 5th March 2019 (ISCRTN85899451).

Secondary research use of personal medical data: patient attitudes towards data donation

Background The SARS-CoV-2 pandemic has highlighted once more the great need for comprehensive access to, and uncomplicated use of, pre-existing patient data for medical research. Enabling secondary research-use of patient-data is a prerequisite for the efficient and sustainable promotion of translation and personalisation in medicine, and for the advancement of public-health. However, balancing the legitimate interests of scientists in broad and unrestricted data-access and the demand for individual autonomy, privacy and social justice is a great challenge for patient-based medical research. Methods We therefore conducted two questionnaire-based surveys among North-German outpatients (n = 650) to determine their attitude towards data-donation for medical research, implemented as an opt-out-process. Results We observed a high level of acceptance (75.0%), the most powerful predictor of a positive attitude towards data-donation was the conviction that every citizen has a duty to contribute to the improvement of medical research (> 80% of participants approving data-donation). Interestingly, patients distinguished sharply between research inside and outside the EU, despite a general awareness that universities and public research institutions cooperate with commercial companies, willingness to allow use of donated data by the latter was very low (7.1% to 29.1%, depending upon location of company). The most popular measures among interviewees to counteract reservations against commercial data-use were regulation by law (61.4%), stipulating in the process that data are not sold or resold (84.6%). A majority requested control of both the use (46.8%) and the protection (41.5%) of the data by independent bodies. Conclusions In conclusion, data-donation for medical research, implemented as a combination of legal entitlement and easy-to-exercise-right to opt-out, was found to be widely supported by German patients and therefore warrants further consideration for a transposition into national law.

Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection—the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval.

Ethics experts and fetal patients: a proposal for modesty

Background Ethics consultation is recognized as an opportunity to share responsibility for difficult decisions in prenatal medicine, where moral intuitions are often unable to lead to a settled decision. It remains unclear, however, if the general standards of ethics consultation are applicable to the very particular setting of pregnancy. Main text We sought to analyze the special nature of disagreements, conflicts and value uncertainties in prenatal medicine as well as the ways in which an ethics consultation service (ECS) could possibly respond to them and illustrated our results with a case example. Ethics facilitation and conflict mediation, currently, have no broadly consented normative framework encompassing prenatal diagnosis and therapy as well as reproductive choice to draw on. Even so, they can still be helpful instruments for ethically challenging decision-making in prenatal medicine provided two additional rules are respected: For the time being, ECSs should (a) refrain from issuing content-heavy recommendations in prenatal medicine and (b) should not initiate conflict mediations that would involve the pregnant woman or couple as a conflict party. Conclusion It seems to be vital that ethics consultants as well as health care professionals acknowledge the current limitations and pitfalls of ethics consultation in prenatal medicine and together engage in the advancement of standards for this particularly complex setting.

Navigating abortion law dilemmas: experiences and attitudes among Ethiopian health care professionals

Background Ethiopia’s 2005 abortion law improved access to legal abortion. In this study we examine the experiences of abortion providers with the revised abortion law, including how they view and resolve perceived moral challenges. Methods Thirty healthcare professionals involved in abortion provisions in Addis Ababa were interviewed. Transcripts were analyzed using systematic text condensation, a qualitative analysis framework. Results Most participants considered the 2005 abortion law a clear improvement—yet it does not solve all problems and has led to new dilemmas. As a main finding, the law appears to have opened a large space for professionals’ individual interpretation and discretion concerning whether criteria for abortion are met or not. Regarding abortion for fetal abnormalities, participants support the woman’s authority in deciding whether to choose abortion or not, although several saw these decisions as moral dilemmas. All thought that abortion was a justified choice when a diagnosis of fetal abnormality had been made. Conclusion Ethiopian practitioners experience moral dilemmas in connection with abortion. The law places significant authority, burden and responsibility on each practitioner.