Testing the waters: Ethical considerations for including PrEP in a phase IIb HIV vaccine efficacy trial.

BACKGROUND: The field of HIV prevention research has recently experienced some mixed results in efficacy trials of pre-exposure prophylaxis, vaginal microbicides, and HIV vaccines. While there have been positive trial results in some studies, in the near term, no single method will be sufficient to quell the epidemic. Improved HIV prevention methods, choices among methods, and coverage for all at-risk populations will be needed. The emergence of partially effective prevention methods that are not uniformly available raises complex ethical and scientific questions regarding the design of ongoing prevention trials. METHODS: We present here an ethical analysis regarding inclusion of pre-exposure prophylaxis in an ongoing phase IIb vaccine efficacy trial, HVTN 505. This is the first large vaccine efficacy trial to address the issue of pre-exposure prophylaxis, and the decisions made by the protocol team were informed by extensive stakeholder consultations. The key ethical concerns are analyzed here, and the process of stakeholder engagement and decision-making described. DISCUSSION: This discussion and analysis will be useful as current and future research teams grapple with ethical and scientific study design questions emerging with the rapidly expanding evidence base for HIV prevention.

To What did They Consent? Understanding Consent Among Low Literacy Participants in a Microbicide Feasibility Study in Mazabuka, Zambia.

We conducted a study to review the consenting process in a vaginal microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants' understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations.

Study participants incentives, compensation and reimbursement in resource-constrained settings.

INTRODUCTION: Controversies still exists within the research fraternity on the form and level of incentives, compensation and reimbursement to study participants in resource-constrained settings. While most research activities contribute significantly to advancement of mankind, little has been considered in rewarding directly the research participants from resource-constrained areas. METHODS: A study was conducted in Zimbabwe to investigate views and expectations of various stakeholders on study participation incentives, compensation and reimbursement issues. Data was collected using various methods including a survey of about 1,008 parents/guardians of school children participating in various immunological cohort studies and parasitology surveys. Community advisory boards (CABs) at 9 of the sites were also consulted. Further, information was gathered during discussions held at a basic research ethics training workshop. The workshop had 45 participants that including 40 seasoned Zimbabwean researchers and 5 international research collaborators. RESULTS: About 90% (907) of the study participants and guardians expected compensation of reasonable value, in view of the researchers' value and comparison to other sites regardless of economic status of the community. During discussion with researchers at a basic ethics training workshop, about 80% (32) believed that decisions on level of compensation should be determined by the local research ethics committees. While, the few international research collaborators were of the opinion that compensation should be in accordance with local guidelines, and incentives should be in line with funding. Both the CAB members and study participants expressed that there should be a clear distinction between study incentive and compensation accorded to individual and community expectations on benefits from studies. However, CABs expressed that their suggestions on incentives and compensation are often moderated by the regulatory authorities who cite fear of unknown concerns. CONCLUSION: Overall, both personal and community benefits need to be considered collectively in future studies to be conducted in resource-constrained communities. There is projected fear that recruitment in future may be a challenge, now that almost every community, has somehow been reached and participated in some form of studies. A major concern on reimbursement, compensation or incentives should be internationally pegged regardless of different economic status of the individuals or communities where the study is to be conducted.

Maintaining respect and fairness in the usage of stored shared specimens.

BACKGROUND: Every year, research specimens are shipped from one institution to another as well as across national boundaries. A significant proportion of specimens move from poor to rich countries. Concerns are always raised on the future usage of the stored specimens shipped to research institutions from developing countries. Creating awareness of the processes is required in all sectors involved in biomedical research. To maintain fairness and respect in sharing biomedical specimens and research products requires safeguarding by Ethics Review Committees in both provider and recipient institutions. Training in basic ethical principles in research is required to all sectors involved in biomedical research so as to level up the research playing field. DISCUSSION: By agreeing to provide specimens, individuals and communities from whom samples are collected would have placed their trust and all ensuing up-keep of the specimens to the researchers. In most collaborative set-up, laid down material transfer agreements are negotiated and signed before the shipment of specimens. Researchers, research ethics committees (RECs) and institutions in the countries of origin are supposed to serve as overseers of the specimens. There is need to advocate for honesty in sample handling and sharing, and also need to oversee any written commitments by researchers, RECs and institutions at source as well as in recipient institution. Commitments from source RECs and Institutional Review Boards (IRBs) and in the receiving institution on overseeing the future usage of stored specimens are required; including the ultimate confirmation abiding by the agreement. Training in ethical issues pertaining to sample handling and biomedical research in general is essential at all levels of academic pursuit. While sharing of biological specimens and research data demands honesty and oversight by ethical regulatory agents from both institutions in developing country and recipient institutions in developed countries. CONCLUDING SUMMARY: Archiving of biological specimens requires reconsideration for the future of biomedical findings and scientific break-throughs. Biomedical ethical regulations still need to established clear viable regulations that have vision for the future of science through shared and archived samples. This discussion covers and proposes essential points that need to be considered in view of future generations and scientific break-throughs. The discussion is based on the experience of working in resource-limited settings, the local regulatory laws and the need to refine research regulations governing sharing and storage of specimens for the future of science.

Evaluating institutional capacity for research ethics in Africa: a case study from Botswana.

BACKGROUND: The increase in the volume of research conducted in Low and Middle Income Countries (LMIC), has brought a renewed international focus on processes for ethical conduct of research. Several programs have been initiated to strengthen the capacity for research ethics in LMIC. However, most such programs focus on individual training or development of ethics review committees. The objective of this paper is to present an approach to institutional capacity assessment in research ethics and application of this approach in the form of a case study from an institution in Africa. METHODS: We adapted the Octagon model originally used by the Swedish International Development Cooperation Agency to assess an organization along eight domains in research ethics: basic values and identity; structure and organization; ability to carry out activities; relevance of activities to stated goals; capacity of staff and management; administrative, financing and accounting systems; its relations with target groups; and the national context. We used a mixed methods approach to collect empirical data at the University of Botswana from March to December 2010. RESULTS: The overall shape of the external evaluation Octagon suggests that strengths of the University of Botswana are in the areas of structure, relevance, production and identity; while the university still needs more work in the areas of systems of finance, target groups, and environment. The Octagons also show the similarities and discrepancies between the 'external' and 'internal' evaluations and provide an opportunity for exploration of these different assessments. For example, the discrepant score for 'identity' between internal and external evaluations allows for an exploration of what constitutes a strong identity for research ethics at the University of Botswana and how it can be strengthened. CONCLUSIONS: There is a general lack of frameworks for evaluating research ethics capacity in LMICs. We presented an approach that stresses evaluation from both internal and external perspectives. This case study highlights the university's rapid progress in developing research ethics capacity and points to some notable areas for improvement. We believe that such an empirically-driven and participatory assessment allows a more holistic measurement and promotion of institutional capacity strengthening for research ethics in LMICs.

Improving understanding of clinical trial procedures among low literacy populations: an intervention within a microbicide trial in Malawi.

BACKGROUND: The intervention reported in this paper was a follow up to an empirical study conducted in Malawi with the aim of assessing trial participants' understanding of randomisation, double-blinding and placebo use. In the empirical study, the majority of respondents (61.1%; n=124) obtained low scores (lower than 75%) on understanding of all three concepts under study. Based on these findings, an intervention based on a narrative which included all three concepts and their personal implications was designed. The narrative used daily examples from the field of Agriculture because Malawi has an agro-based economy. METHODS: The intervention was tested using a sample of 36 women who had been identified as low scorers during the empirical study. The 36 low scorers were randomly assigned to control (n=18) and intervention arms (n=18). The control arm went through a session in which they were provided with standard informed consent information for the microbicide trial. The intervention arm went through a session in which they were provided with a narrative in ChiChewa, the local language, with the assistance of a power point presentation which included pictures as well as discussions on justification and personal implications of the concepts under study. RESULTS: The findings on the efficacy of the intervention suggest that the 3 scientific concepts and their personal implications can be understood by low literacy populations using simple language and everyday local examples. The findings also suggest that the intervention positively impacted on understanding of trial procedures under study, as 13 of the 18 women in the intervention arm, obtained high scores (above 75%) during the post intervention assessment and none of the 18 in the control arm obtained a high score. Using Fischer's exact test, it was confirmed that the effect of the intervention on understanding of the three procedures was statistically significant (p=0.0001). CONCLUSIONS: Potential trial participants can be assisted to understand key clinical trial procedures, their justification and personal implications by using innovative tailored local narratives.

Moral distress in nursing practice in Malawi.

The aim of this study was to explore the existence of moral distress among nurses in Lilongwe District of Malawi. Qualitative research was conducted in selected health institutions of Lilongwe District in Malawi to assess knowledge and causes of moral distress among nurses and coping mechanisms and sources of support that are used by morally distressed nurses. Data were collected from a purposive sample of 20 nurses through in-depth interviews using a semi-structured interview guide. Thematic analysis of qualitative data was used. The results show that nurses, irrespective of age, work experience and tribe, experienced moral distress related to patient/nursing care. The major distressing factors were inadequate resources and lack of respect from patients, guardians, peers and bosses. Nurses desire teamwork and ethics committees in their health institutions as a means of controlling and preventing moral distress. There is a need for creation of awareness for nurses to recognize and manage moral distress, thus optimizing their ability to provide quality and uncompromised nursing care.

Evaluating industry attempts to influence public health: Applying an ethical framework in understanding commercial determinants of health.

Objectives: This paper explores industry influence on public health using a specific case study and applies an established ethical framework based on eleven principles to explore Commercial Determinants of Health (CDoH). It demonstrates an application of these principles to evaluate the ethical integrity of industry strategies and practices and their impacts on public health. Methods: Using eleven a priori, deductive, ethical principles as codes, this paper conducted an in-depth analysis of 19 e-mail chains and accompanying documents made publicly available through the Freedom of Information Act (FOIA) from U.S. Right to Know (USRTK) sent between Coca-Cola representatives, lobbyists, academics, and the International Life Sciences Institute (ILSI), founded by former Coca-Cola executives. Results: The three principles violated most frequently amongst the documents were consumer sovereignty (n = 22), evidence-informed actions (n = 21), and transparency (n = 20). Similarly, codes that featured most regularly across documents were transparency (13 out of 19 documents), consumer sovereignty (13 out of 19 documents), evidence-informed actions (9 out of 19 documents), and social justice and equity (9 out of 19 documents). All eleven principles were applied at least four times throughout the documents; however, responsiveness (z = 12), moral responsibility (z = 16), and holism (z = 30) were the least relevant to the data set. Conclusions: This case study of Coca-Cola demonstrates the usefulness of this ethics framework in reviewing actions of corporate actors in the promotion of products that are harmful to human health. It shows that the industry at times has low ethical integrity in their various strategies and practices to promote their products despite the negative impacts of these products on public health.

COVID-19 vaccine mandate for healthcare workers in the United States: a social justice policy.

INTRODUCTION: Vaccination is the most effective strategy to mitigating COVID-19 and restoring societal function. As the pandemic evolves with no certainty of a herd immunity threshold, universal vaccination of at-risk populations is desirable. However, vaccine hesitancy threatens the return to normalcy, and healthcare workers (HCWs) must embrace their ambassadorial role of shoring up vaccine confidence. Unfortunately, voluntary vaccination has been suboptimal among HCWs in the United States, a priority group for whom immunization is essential for maintaining health system capacity and the safety of high-risk patients in their care. Consequently, some health systems have implemented mandates to improve compliance. AREAS COVERED: This article discusses the ethical and practical considerations of mandatory COVID-19 vaccination policies for HCWs utilizing some components of the World Health Organization's framework and the unique context of a pandemic with evolving infection dynamics. EXPERT OPINION: COVID-19 vaccine mandates for universal immunization of HCWs raise ethical and practical debates about their appropriateness, especially when the vaccines are pending full approval in most jurisdictions. Given the superiority of the vaccines to safety and testing protocols and their favorable safety profile, we encourage health systems to adopt vaccination mandates through participatory processes that address the concerns of stakeholders.

Shifts in UNAIDS ethics guidance and implications for ethics review of preventive HIV vaccine trials.

INTRODUCTION: A major change in the ethics framework for preventive HIV vaccine trials worldwide is the release of the UNAIDS 2021 ethical considerations in HIV prevention trials. This new guidance comes at an exciting time when there are multiple HIV vaccine efficacy trials in the field. Research Ethics Committees (RECs) or Institutional Review Boards are a most likely audience for these guidelines. Our objective is to highlight shifts in ethics recommendations from the earlier 2012 UNAIDS guidance. DISCUSSION: We review recommendations related to four key issues, namely standard of prevention, post-trial access to safe and effective vaccines, enrolment of adolescents and enrolment of pregnant women. We outline implications and make recommendations for the ethics review process, including suggested lines of inquiry by RECs and responses by applicants. CONCLUSIONS: There have been several shifts in the UNAIDS ethics guidance with implications for HIV vaccine researchers submitting applications for initial ethics review or re-certification, and for RECs conducting such reviews. This review may assist RECs in a more efficient and consistent application of ethics recommendations. However, additional tools and training may further help stakeholders comply with new UNAIDS ethics recommendations during protocol development and ethics review.

Proceedings of an expert workshop on community agreement for gene drive research in Africa - Co-organised by KEMRI, PAMCA and Target Malaria.

Gene drive research is progressing towards future field evaluation of modified mosquitoes for malaria control in sub-Saharan Africa. While many literature sources and guidance point to the inadequacy of individual informed consent for any genetically modified mosquito release, including gene drive ones, (outside of epidemiological studies that might require blood samples) and at the need for a community-level decision, researchers often find themselves with no specific guidance on how that decision should be made, expressed and by whom. Target Malaria, the Kenya Medical Research Institute and the Pan African Mosquito Control Association co-organised a workshop with researchers and practitioners on this topic to question the model proposed by Target Malaria in its research so far that involved the release of genetically modified sterile male mosquitoes and how this could be adapted to future studies involving gene drive mosquito releases for them to offer reflections about potential best practices. This paper shares the outcomes of that workshop and highlights the remaining topics for discussion before a comprehensive model can be designed.

How Should Vaccine Campaigns Balance Need for Clear Communication Against Need for Timely Administration of Large-Scale Programs?

Limited understanding of public health disease prevention programs often leads to resistance, which ultimately results in low vaccine uptake. This article suggests how public health practitioners can improve public understanding of cervical cancer and HPV vaccination programs, which is key to improving health literacy, using culturally appropriate materials and approaches to boost public acceptance of vaccine programs.

Commercial determinants of health: an ethical exploration.

OBJECTIVES: This paper seeks to contribute toward a better understanding of commercial determinants of health by proposing a set of ethical principles that can be used by researchers and other health actors in understanding and addressing Commercial Determinants of Health (CDoH). METHODS: The paper is mainly based on a systematic review and qualitative analysis of the existing literature on CDoH and public health ethics frameworks. We conducted searches using selected search engines (Google Scholar and Pubmed). For ethical challenges relating to CDOH, our searches in Google Scholar yielded 17 papers that discussed ethical challenges that affect CDoH. For ethical frameworks relevant for CDOH, our searches in Google Scholar and Pubmed yielded 15 papers that clearly described bioethical models including relevant ethical principles. Additionally, we consulted eight experts working on CDoH. Through these two methods, we were able to identify ethical challenges as well as norms and values related to CDoH that we offer as candidates to comprise a foundational ethics framework for CDoH. RESULTS: Discussing risk factors associated with CDH frequently brings public health into conflict with the interests of industry actors in the food, automobile, beverage, alcohol, ammunition, gaming and tobacco industries including conflict between profit-making and public health. We propose the following candidate ethical principles that can be used in addressing CDoH: moral responsibility, nonmaleficence, social justice and equity, consumer sovereignty, evidence-informed actions, responsiveness, accountability, appropriateness, transparency, beneficence and holism. CONCLUSIONS: We hope that this set of guiding principles will generate wider global debate on CDoH and help inform ethical analyses of corporate actions that contribute to ill health and policies aimed at addressing CDoH. These candidate principles can guide researchers and health actors including corporations in addressing CDoH.

Understanding Ethical, Legal and Societal Issues (ELSIs) in Human Biobanking and Genomics for Research and Healthcare in Zimbabwe: The Genomics Inheritance Law Ethics and Society (GILES) initiative.

Biobanks and human genomics applications are key for understanding health, disease and heredity in Africa and globally. Growing interest in these technologies calls for strengthening relevant legal, ethical and policy systems to address knowledge disparities and ensure protection of society, while supporting advancement of science. In Zimbabwe there is limited understanding of ethical, legal, and societal issues (ELSI) for biobanking and genomics. The Genomics Inheritance Law Ethics and Society (GILES) initiative was established in 2015 to explore the current status and gaps in the ethical and legal frameworks, knowledge among various stakeholders, and to establish capacity for addressing ELSI of biobanking and genomics as applied in biomedical and population research, and healthcare. A multi-methods approach was applied including document reviews, focus group discussions and in-depth interviews among health and research professionals, and community members in six provinces comprising urban, peri-urban and rural areas. Emerging findings indicates a need for updating guidelines and policies for addressing ELSI in biobanking and genomics research in Zimbabwe. Emerging terminologies such as biobanking and genomics lack clarity suggesting a need for increased awareness and educational tools for health professionals, research scientists and community members. Common concerns relating to consent processes, sample and data use and sharing, particularly where there is trans-national flow of biospecimens and data, call for nationally tailored ELSI frameworks aligned to regional and international initiatives. This paper describes the strategy undertaken for the development and implementation of the GILES project and discusses the importance of such an initiative for characterisation of ELSI of human biobanking and genomics in Zimbabwe and Africa. Conducting this explorative study among a wide range of stakeholders over a countrywide geographical regions, established one of the most comprehensive studies for ELSI of human biobanking and genomics in Africa.