Developing and piloting a context-specified ethics framework for health technology assessment: the South African Values and Ethics for Universal Health Coverage approach.

OBJECTIVES: While ethics has been identified as a core component of health technology assessment (HTA), there are few examples of practical, systematic inclusion of ethics analysis in HTA. Some attribute the scarcity of ethics analysis in HTA to debates about appropriate methodology and the need for ethics frameworks that are relevant to local social values. The "South African Values and Ethics for Universal Health Coverage" (SAVE-UHC) project models an approach that countries can use to develop HTA ethics frameworks that are specific to their national contexts. METHODS: The SAVE-UHC approach consisted of two phases. In Phase I, the research team convened and facilitated a national multistakeholder working group to develop a provisional ethics framework through a collaborative, engagement-driven process. In Phase II, the research team refined the model framework by piloting it through three simulated HTA appraisal committee meetings. Each simulated committee reviewed two case studies of sample health interventions: opioid substitution therapy and either a novel contraceptive implant or seasonal influenza immunization for children under five. RESULTS: The methodology was fit-for-purpose, resulting in a context-specified ethics framework and producing relevant findings to inform application of the framework for the given HTA context. CONCLUSIONS: The SAVE-UHC approach provides a model for developing, piloting, and refining an ethics framework for health priority-setting that is responsive to national social values. This approach also helps identify key facilitators and challenges for integrating ethics analysis into HTA processes.

Ethical and societal challenges in penis transplantation.

PURPOSE OF REVIEW: To review the current understanding of the ethical and societal difficulties of penile transplantation. RECENT FINDINGS: Penile transplantation, as with other forms of vascularized composite allotransplantation, has increasing acceptance in society but is still not entirely accepted. Guidelines aiming to help guide future penile transplant programs in an ethical and scientific safe manner were created. Controversies regarding the economic impact, patient safety, and the rights of the patients choosing penile transplant remains. SUMMARY: Penile transplantation has excellent functional and cosmetic results in the short-term and medium-term. The penis, similar to the face in facial transplantation, carries emotional gravity that relates to visible body parts of another that live forth in a tangible manner contributing to psychological and ethical challenges for both the individual and society more broadly, healthcare administrators, and healthcare workers. In the context of these challenges, controversies emerge related to issues of judgment about what society can and wants to afford. Effects of toxic immunosuppression in a nonlife saving life-enhancing procedure, as well as costs, become arguments that have to be considered in the context of ethical and societal challenges.

Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up.

INTRODUCTION: Ritual circumcision complicated by gangrene is a leading cause of penile loss in young men in South Africa. This deeply rooted cultural tradition is unlikely to be abolished. Conventional reconstructive techniques using free vascularised tissue flaps with penile implants are undesirable in this often socioeconomically challenged group because donor site morbidity can hinder manual labour and vigorous sexual activity might lead to penile implant extrusion. The psychosociological effects of penile loss in a young man are devastating and replacing it with the same organ is likely to produce the maximum benefit. METHODS: We first performed a cadaver-to-cadaver penile transplantation as preparation. After approval from the Human Research Ethics Committee was obtained, we recruited potential recipients. We screened the potential participants for both physical and psychological characteristics, including penile stump length, and emotional suitability for the procedure. A suitable donor became available and the penis was harvested. We surgically prepared the penile stump of the recipient and attached the penile graft. Immunosuppression treatment with antithymyocyte globulin, methylprednisolone, tacrolimus, mycophenolate mofetil, and prednisone were commenced. Tadalafil at 5 mg once per day was commenced after 1 week as penile rehabilitation and was continued for 3 months. We collected on quality-of-life scores (Short Form 36 version 2 [SF-36v2] questionnaires) before surgery and during follow-up and measured erectile function (International Index for Erectile Function [IIEF] score) and urine flow rates at 24 months post transplant. FINDINGS: The warm ischaemia time for the graft after removal was 4 min and the cold ischaemia time was 16 h. The surgery lasted 9 h. An arterial thrombus required urgent revision 8 h after the operation. On post operative day 6, an infected haematoma and an area of proximal skin necrosis were surgically treated. The recipient was discharged after 1 month and first reported satisfactory sexual intercourse 1 week later (despite advice to the contrary). The recipient reported regular sexual intercourse from 3 months after the operation. An episode of acute kidney injury at 7 months was reversed by reducing the tacrolimus dose to 14 mg twice per day. At 8 months after surgery, the patient had a skin infection with phaeohyphomycosis due to Alternaria alternata, which we treated with topical antifungal medication. Quality-of-life scores improved substantially after the operation (SF-36v2 mental health scores improved from 25 preoperatively, to 57 at 6 months and 46 at 24 months post transplant; physical health scores improved from 37 at baseline to 60 at 6 months and 59 at 24 months post-transplant). At 24 months, measured maximum urine flow rate (16·3 mL/s from a volume voided of 109 mL) and IIEF score (overall satisfaction score of 8 from a maximum of 10) were normal, showing normal voiding and erectile function, respectively. INTERPRETATION: Penile transplantation restored normal physiological functions in this transplant recipient without major complications in the first 24 months. FUNDING: Department of Health, Western Cape Government.

Exploring the ethics of global health research priority-setting.

BACKGROUND: Thus far, little work in bioethics has specifically focused on global health research priority-setting. Yet features of global health research priority-setting raise ethical considerations and concerns related to health justice. For example, such processes are often exclusively disease-driven, meaning they rely heavily on burden of disease considerations. They, therefore, tend to undervalue non-biomedical research topics, which have been identified as essential to helping reduce health disparities. In recognition of these ethical concerns and the limited scholarship and dialogue addressing them, we convened an international workshop in September 2015. The workshop aimed to initiate discussion on the appropriate relationship between global and national levels of health research priority-setting and to begin exploring what might be ethically required for priority-setting at each of those levels. MAIN TEXT: This paper comprises our reflections following the workshop. Its main objective is to launch a research agenda for the ethics of global health research priority-setting. We identify three domains of global health research priority-setting-scope, underlying values and substantive requirements, and procedural considerations. For each domain, specific research questions are highlighted and why they need to be explored is explained. Some preliminary thoughts and normative arguments as to how the research questions might be answered are also offered. For example, we provide initial ideas about the appropriate relationship between different priority-setting levels and what values and substantive considerations should guide or underpin global health research priority-setting as a matter of justice. CONCLUSION: We anticipate that framing a new research agenda for the ethics of global health research priority-setting will spur ethicists, researchers, and policymakers to refocus their efforts on developing more rigorous and ethically sound approaches to priority-setting.

The Social Value of Health Research and the Worst Off.

In this article we argue that the social value of health research should be conceptualized as a function of both the expected benefits of the research and the priority that the beneficiaries deserve. People deserve greater priority the worse off they are. This conception of social value can be applied for at least two important purposes: (1) in health research priority setting when research funders, policy-makers, or researchers decide between alternative research projects; and (2) in evaluating the ethics of proposed research proposals when research ethics committees (RECs) assess whether the social value of the research is sufficient to justify the risks and burdens to research participants and others. In assessing how far a proposed research project will advance the interests of people who are more disadvantaged, research priority setters and RECs should examine (at least) the diseases that the research targets and the type of research. Just as certain diseases impose a greater burden on people who are more disadvantaged, so certain types of intervention and forms of research are more likely to benefit people who are more disadvantaged. We outline which populations are likely to be representative of the global worst off and identify what types of health research, and which disease categories, are priorities for these populations.

Lessons learned from the world's first successful penis allotransplantation.

We performed a successful penis allotransplantation on 11 December 2014. Sharing the lessons learned might help more patients in need to be treated this way. We divided the project into manageable segments that was each overseen by an expert. The ethical review and conduct paved the way for a publically acceptable and successful project. Screening for a psychological stable recipient is important. The most difficult part of the project was finding a donor penis. This was successfully negotiated with the family of a brain dead donor by creating a neo-phallus for the donor, thereby maintaining the dignity of the donor. Working with transplant coordinators that are sympathetic to aphallic men is crucial. Surgeons versed in microvascular techniques is a critical part of the team. Transplant immunologists have to adapt to treat composite tissue transplantation patients.

The Value of Explicit, Deliberative, and Context-Specified Ethics Analysis for Health Technology Assessment: Evidence From a Novel Approach Piloted in South Africa.

OBJECTIVES: This article explores the perceived value, including associated strengths and challenges, of using a context-specified ethics framework to guide deliberative health technology appraisals. METHODS: The South African Values and Ethics for Universal Health Coverage (SAVE-UHC) approach, piloted in South Africa, consisted of 2 phases: (1) convening a national multistakeholder working group to develop a provisional ethics framework and (2) testing the provisional ethics framework through simulated health technology assessment appraisal committee meetings (SACs). Three SACs each reviewed 2 case studies of sample health interventions using the framework. Participants completed postappraisal questionnaires and engaged in focus group discussions. RESULTS: The SACs involved 27 participants across 3 provinces. Findings from the postappraisal questionnaires demonstrated general support for the SAVE-UHC approach and content of the framework, high levels of satisfaction with the recommendations produced, and general sentiment that participants were able to actively contribute to appraisals. Qualitative data showed participants perceived using a context-specified ethics framework in deliberative decision making: (1) supported wider consideration of and deliberation about morally relevant features of the health coverage decisions, thereby contributing to quality of appraisals; (2) could improve transparency; and (3) offered benefits to those directly involved in the priority-setting process. Participants also identified some challenges and concerns associated with the approach. CONCLUSIONS: The SAVE-UHC approach presents a novel way to develop and pilot a locally contextualized, explicit ethics framework for health priority setting. This work highlights how the combination of a context-specified ethics framework and structured deliberative appraisals can contribute to the quality of health technology appraisals and transparency of health priority setting.

Access to treatment in HIV prevention trials: perspectives from a South African community.

Access to treatment, in HIV vaccine trials (HVTs), remains ethically controversial. In most prevention trials, including in South Africa, participants who seroconvert are referred to publicly funded programmes for treatment. This strategy is problematic when there is inadequate and uneven access to public sector antiretroviral therapy (ART) and support resources. The responsibilities, if any, of researchers, sponsors and public health authorities involved in HVTs has been hotly debated among academics, scholars, representatives of international organizations and sponsors. However, there is little published on community perceptions. Recent guidance asserts that communities should make inputs into treatment and care decisions. This qualitative study explored a South African community's perceptions of who should provide what to HVT participants as well as how and why this should be done. Twenty-nine adults working at or attending five primary health care clinics in two rural areas in KwaZulu-Natal participated in in-depth interviews. Respondents expressed that researchers should 'help participants to access' treatment and care 'because they are in a position to do so' and 'are in a relationship with' trial participants. Respondents suggested that researchers could help by 'facilitating referral' until such time that participants can access care and treatment on their own. We highlight a series of implications for researchers in HVTs, including their need to be aware of prospective participants' considerable trust in and respect for researchers, the responsibility that this places on them, and the need for clear communication with communities so as not to erode community trust.

Stakeholder perspectives on ethical challenges in HIV vaccine trials in South Africa.

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open-ended, in-depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research stakeholders, the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment. While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical-legal framework and research policies, and, for further research.

Perceived enablers and constraints of motivation to conduct undergraduate research in a Faculty of Medicine and Health Sciences: What role does choice play?

BACKGROUND: Enhancing evidence-based practice and improving locally driven research begins with fostering the research skills of undergraduate students in the medical and health sciences. Research as a core component of undergraduate curricula can be facilitated or constrained by various programmatic and institutional factors, including that of choice. Self-Determination Theory (SDT) provides a framework for understanding the influence of choice on student motivation to engage in research. AIM: This study aimed to document the enablers and constraints of undergraduate research at a South African Faculty of Medicine and Health Sciences (FMHS) and to explore how the presence or absence of choice influenced students' engagement with research in this context. METHODS: An exploratory descriptive design was adopted. Undergraduate students who had conducted research and undergraduate programme staff were recruited through purposive sampling. Semi-structured interviews were transcribed and thematically analysed. Findings were interpreted using SDT, focusing on how choice at various levels affects motivation and influences research experiences. RESULTS: Many of the programmatic and institutional enablers and constraints-such as time and supervisory availability-were consistent with those previously identified in the literature, regardless of whether research was compulsory or elective. Choice itself seemed to operate as both an enabler and a constraint, highlighting the complexity of choice as an influence on student motivation. SDT provided insight into how programmatic and institutional factors-and in particular choice-supported or suppressed students' needs for autonomy, competence, and relatedness, thereby influencing their motivation to engage in research. CONCLUSION: While programmatic and institutional factors may enable or constrain undergraduate research, individual-level factors such as the influence of choice on students' motivation play a critical role. The implication for curriculum development is that research engagement might be enhanced if levels of choice are structured into the curriculum such that students' needs for autonomy, competence, and relatedness are met.

Racial differences in public perceptions of voluntariness of medical research participants in South Africa.

The reign of apartheid in South Africa was characterized by systematic violation of the human rights of the Black population. Ruling institutions of the country perpetuated and enforced such violations. Consequently, Black South Africans may be apprehensive of scientific research in which the Black population is targeted for participants, regardless of the reason for their being selected. This exploratory study aims to (1) contribute to the relatively limited body of empirical research on the concept of voluntariness and (2) assess racial differences in public perceptions of the voluntariness of medical research participants. We sampled 111 employees from two companies. The sample consisted of 39 Black, 37 Indian, and 38 White participants. A structured questionnaire was used to interview respondents. Results showed that Black respondents scored significantly lower on scores of perceived voluntariness than both Indian and White respondents. These racial differences in perceptions of voluntariness were found to be independent of level of education, knowledge of medical research procedures, and close or personal experience of medical research. Perceptions of voluntariness did not however appear to impact on participants' personal willingness to participate in future research. Implications for recruitment of future health research participants in South Africa are discussed.

The ethical involvement of women in HIV vaccine trials in Africa: discussion paper developed for the African AIDS Vaccine Programme.

HIV disproportionately affects women in developing countries, especially in Southern Africa. Women thus stand to benefit most from a successful HIV vaccine and must participate in trials to test appropriate, gender-specific products. Several HIV vaccine efforts are currently underway in Africa. Participation in HIV vaccine trials requires that participants not only understand the complex nature of trial procedures, but that they also have autonomous decisional capacity to enroll. Given that the risk factors inherent in women's greater vulnerability constitute an intricate mix of biological, economic and social variables, will women's very vulnerability to HIV be an obstacle to ethical participation in vaccine development? This paper addresses some of the challenges underlying the successful recruitment of women into vaccine research and makes research and policy recommendations for the ethical inclusion of women in HIV vaccine trials in Africa.