A scoping review of ethics review processes during public health emergencies in Africa.

BACKGROUND: The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs). METHODS: We searched four electronic databases (Web of Science, PUBMED, MEDLINE Complete, and CINAHL) to identify articles describing ethics review processes during public health emergencies and/or pandemics. We selected and reviewed those articles that were focused on Africa. We charted the data from the retrieved articles including the authors and year of publication, title, country and disease(s) reference, broad areas of (ethical) consideration, paper type, and approach. RESULTS: Of an initial 4536 records retrieved, we screened the titles and abstracts of 1491 articles, and identified 72 articles for full review. Nine articles were selected for inclusion. Of these nine articles, five referenced West African countries including Liberia, Guinea and Sierra Leone, and experiences linked to the Ebola virus disease. Two articles focused on South Africa and Kenya, while the other two articles discussed more general experiences and pitfalls of ethics review during PHEs in Africa more broadly. We found no articles published on ethics review processes in Africa before the 2014 Ebola outbreak, and only a few before the COVID-19 outbreak. Although guidelines on protocol review and approval processes for PHEs were more frequently discussed after the 2014 Ebola outbreak, these did not focus on Africa specifically. CONCLUSIONS: There is a gap in the literature about ethics review processes and preparedness within Africa during PHEs. This paper underscores the importance of these processes to inform practices that facilitate timely, context-relevant research that adequately recognises and reinforces human dignity within the quest to advance scientific knowledge about diseases. This is important to improve fast responses to PHEs, reduce mortality and morbidity, and enhance the quality of care before, during, and after pandemics.

Ethical issues of involving people with intellectual disabilities in genomic research: a scoping review protocol.

Background: Psychiatric genomic research is a growing field of research in Africa that is looking at epigenetics of psychiatric disorders; within which a specific focus is neurodevelopmental disorders including intellectual disability (ID). Conducting this type of research is important to identify etiologies and possible interventions or areas for further research. However, genomic research generally, and psychiatric genomic research, faces many social, ethical, cultural, and legal issues; research involving people with ID is particularly challenging. All research stakeholders - researchers, research review bodies, regulators, patient groups - generally agree that involving people with ID require several considerations, including extra protection. It is also recognized that not involving people with ID in research that is relevant to them means that opportunities to learn on specific issues including lived experiences are missed. In this scoping review, we aim to describe the range of ethical and social-cultural issues concerning involvement of people with intellectual disability in genomic research from existing literature. Methods: This scoping review will be conducted based on the Joanna Briggs Institute guidance for scoping review and reported using the PRISMA-ScR guidelines. Iterative review stages will include systematic search of six databases (Embase, Ovid Global Health, PubMed, Scopus, PsycInfo and Web of Science core collection), screening, charting and synthesis of the data. Forward and backward citation screening will also be done for the articles included in the final review. We will include peer reviewed journal articles, guidance documents and reports. Screening and selection of studies based on the eligibility criteria will be done independently by three reviewers; conflicts will be resolved through discussion with a third reviewer and other experts. Results: The results will be included in the scoping review publication. Conclusions: This scoping review will identify key areas of ethical tensions and possible solutions and inform opportunities for empirical ethics studies.

The hidden emotional labour behind ensuring the social value of research: Experiences of frontline health policy and systems researchers based in Kenya during COVID-19.

Health policy and systems research (HPSR) is a multi-disciplinary, largely applied field of research aimed at understanding and strengthening the performance of health systems, often with an emphasis on power, policy and equity. The value of embedded and participatory HPSR specifically in facilitating the collection of rich data that is relevant to addressing real-world challenges is increasingly recognised. However, the potential contributions and challenges of HPSR in the context of shocks and crises are not well documented, with a particular gap in the literature being the experiences and coping strategies of the HPSR researchers who are embedded in health systems in resource constrained settings. In this paper, we draw on two sets of group discussions held among a group of approximately 15 HPSR researchers based in Nairobi, Kenya, who were conducting a range of embedded HPSR studies throughout the COVID-19 pandemic. The researchers, including many of the authors, were employed by the KEMRI-Wellcome Trust Research Programme (KWTRP), which is a long-standing multi-disciplinary partnership between the Kenya Medical Research Institute and the Wellcome Trust with a central goal of contributing to national and international health policy and practice. We share our findings in relation to three inter-related themes: 1) Ensuring the continued social value of our HPSR work in the face of changing priorities; 2) Responding to shifting ethical procedures and processes at institutional and national levels; and 3) Protecting our own and front-line colleagues' well-being, including clinical colleagues. Our experiences highlight that in navigating research work and responsibilities to colleagues, patients and participants through the pandemic, many embedded HPSR staff faced difficult emotional and ethical challenges, including heightened forms of moral distress, which may have been better prevented and supported. We draw on our findings and the wider literature to discuss considerations for funders and research leads with an eye to strengthening support for embedded HPSR staff, not only in crises such as the on-going COVID-19 pandemic, but also more generally.

Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.

Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.

Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.

Rethinking benefit sharing in collaborative human genetic research from an Afrocommunitarian perspective.

This article draws on reflections about humanness, friendliness and partiality, in the writings of Afro-communitarians to develop principles for thinking critically about why benefit sharing, what may count as benefits within the context of human research in Africa and the limits of the obligation of benefit sharing. Suppose the thinking about humanness, friendliness, and partiality in Afro-communitarianism were the foundation of human genetic research in Africa, then, individuals who have contributed to research or borne its burden would benefit from its rewards. This is even more important if participants have pressing needs that researchers and/or research institutions can help ease. A failure to aid sample contributors and data providers in need when researchers and research institutions can-as well as an indifference to the serious needs of contributors-are failures to exhibit friendliness in the relevant ways. Finally, though providing benefits to contributors can be an important way of showing humanity to them, nonetheless, this obligation is not absolute and may be limited by the stronger obligation of shared experience-to advance science. Studies are still required to inquire how well these norms will work in practice and inform regulatory and legal frameworks.

Pandemic preparedness and responsiveness of research review committees: lessons from review of COVID-19 protocols at KEMRI Wellcome Trust Research Programme in Kenya.

Background: The scale of the COVID-19 pandemic and novelty of SARS-CoV-2 presented unprecedented challenges in the review of COVID-19 protocols. We investigated how research at the Kenya Medical Research Institute - Wellcome Trust Research Programme (KWTRP) was reviewed, including by institutional and national level committees. Methods: A document review and in-depth interviews with researchers, regulators and research reviewers were conducted. Documents reviewed included research logs of all protocols submitted between April-1-2020 and March-31-2021, feedback letters from review committees for 10 new COVID-19 protocols (n=42), and minutes from 35 COVID-19 research review meetings. Fifteen in-depth interviews were conducted with respondents purposively selected because of their experience of developing or reviewing COVID-19 protocols at the institution level (n=9 researchers, engagement officers and regulators) or their experience in reviewing proposals at a national-level (n=6 committee members). Data were managed and analyzed using MS Excel and NVivo12. Results: Between April-1-2020 and March-31-2021, 30 COVID-19-related submissions by KWTRP researchers were approved. Changes to the review system included strengthening the online system for protocol submission and review, recruiting more reviewers, and trialing a joint review process. The turnaround time from submission to national approval/rejection over this period was faster than pre-pandemic, but slower than the national committee's target. COVID-19-specific ethics questions centred on: virtual informed consent and data collection; COVID-19 prevention, screening and testing procedures; and the challenges of study design and community engagement during the pandemic. Conclusions: The unprecedented challenges of the pandemic and added bureaucratic requirements created a more complex review process and delayed final approval of research protocols. The feasibility of conducting joint review of research during public health emergencies in Kenya needs further investigation. Consideration of the unique COVID-19 ethics issues raised in this paper might aid expedience in current and future reviews.

Experience of Kenyan researchers and policy-makers with knowledge translation during COVID-19: a qualitative interview study.

OBJECTIVES: Researchers at the KEMRI-Wellcome Trust Research Programme (KWTRP) carried out knowledge translation (KT) activities to support policy-makers as the Kenyan Government responded to the COVID-19 pandemic. We assessed the usefulness of these activities to identify the facilitators and barriers to KT and suggest actions that facilitate KT in similar settings. DESIGN: The study adopted a qualitative interview study design. SETTING AND PARTICIPANTS: Researchers at KWTRP in Kenya who were involved in KT activities during the COVID-19 pandemic (n=6) were selected to participate in key informant interviews to describe their experience. In addition, the policy-makers with whom these researchers engaged were invited to participate (n=11). Data were collected from March 2021 to August 2021. ANALYSIS: A thematic analysis approach was adopted using a predetermined framework to develop a coding structure consisting of the core thematic areas. Any other theme that emerged in the coding process was included. RESULTS: Both groups reported that the KT activities increased evidence availability and accessibility, enhanced policy-makers' motivation to use evidence, improved capacity to use research evidence and strengthened relationships. Policy-makers shared that a key facilitator of this was the knowledge products shared and the regular interaction with researchers. Both groups mentioned that a key barrier was the timeliness of generating evidence, which was exacerbated by the pandemic. They felt it was important to institutionalise KT to improve readiness to respond to public health emergencies. CONCLUSION: This study provides a real-world example of the use of KT during a public health crisis. It further highlights the need to institutionalise KT in research and policy institutions in African countries to respond readily to public health emergencies.

Undertaking Community Engagement for a Controlled Human Malaria Infection Study in Kenya: Approaches and Lessons Learnt.

Human infection studies (HIS) involve deliberately infecting healthy volunteers with disease-causing pathogens under controlled conditions. These studies are "controlled" by way of using specific types of pathogens, including dose, and the availability of emergency medical facilities to research volunteers. Most HIS involve diseases whose treatment is known and are done to accelerate the development of novel therapeutics such as vaccines, to address emerging and existing infectious diseases. Traditionally, HIS have been conducted primarily in high-income countries (HICs) but are now increasingly being conducted in low-and-middle income countries (LMICs). In LMICs settings, HIS are likely to raise concerns among various stakeholders including participating populations and regulatory bodies, that are unfamiliar with this type of research. Deliberately infecting a healthy individual with a disease-causing pathogen seems to go against the normal practice of medicine of "do no harm". Such types of studies can give rise to increased rumors and jeopardize research participation in study activities, including non-HIS research. Community engagement can be one approach to address particular issues that HIS studies raise through meaningfully engaging with communities, where views and voices inform the conduct of HIS studies. In addition, engagement can inform the ethical conduct and acceptability of HIS studies in LMICs settings and provide opportunities for sharing information, listening to, and responding to concerns and views from potential participants, and the larger community in which the study would be conducted. Despite community engagement being an important aspect to consider, very few published and gray literature cover the types of approaches that have been used, and lessons learnt in engagement for HIS. This article outlinesthe community engagement approaches that were used to engage stakeholders and communities for malaria HIS-controlled human malaria infection (CHMI), undertaken in Kilifi, Kenya. It outlines the engagement activities across the research cycle, from activities conducted during protocol development, to planning, and implementation of the study. We discuss the challenges experienced, lessons learnt, and provide some recommendations for engagement around HIS.

Ethical considerations around volunteer payments in a malaria human infection study in Kenya: an embedded empirical ethics study.

Human Infection Studies (HIS) have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid 'undue' levels of inducement to participate. Through this embedded ethics study, involving 97 healthy volunteers and other research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers' attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning.

Strengthening the Health System as a Strategy to Achieving a Universal Health Coverage in Underprivileged Communities in Africa: A Scoping Review.

Universal health coverage (UHC) is defined as people having access to quality healthcare services (e.g., treatment, rehabilitation, and palliative care) they need, irrespective of their financial status. Access to quality healthcare services continues to be a challenge for many people in low- and middle-income countries (LMICs). The aim of this study was to conduct a scoping review to map out the health system strengthening strategies that can be used to attain universal health coverage in Africa. We conducted a scoping review and qualitatively synthesized existing evidence from studies carried out in Africa. We included studies that reported interventions to strengthen the health system, e.g., financial support, increasing work force, improving leadership capacity in health facilities, and developing and upgrading infrastructure of primary healthcare facilities. Outcome measures included health facility infrastructures, access to medicines, and sources of financial support. A total of 34 studies conducted met our inclusion criteria. Health financing and developing health infrastructure were the most reported interventions toward achieving UHC. Our results suggest that strengthening the health system, namely, through health financing, developing, and improving the health infrastructure, can play an important role in reaching UHC in the African context.

A network of empirical ethics teams embedded in research programmes across multiple sites: opportunities and challenges in contributing to COVID-19 research and responses.

Covid-19 continues to teach the global community important lessons about preparedness for research and effective action to respond to emerging health threats. We share the COVID-19 experiences of a pre-existing cross-site ethics network-the Global Health Bioethics Network-which brings together researchers and practitioners from Africa, Europe, and Southeast Asia. We describe the network and its members and activities, and the work-related opportunities and challenges we faced over a one-year period during the pandemic. We highlight the value of having strong and long-term empirical ethics networks embedded across diverse research institutions to be able to: 1) identify and share relevant ethics challenges and research questions and ways of 'doing research'; 2) work with key stakeholders to identify appropriate ways to contribute to the emerging health issue response - e.g., through ethics oversight, community engagement, and advisory roles at different levels; and 3) learn from each other and from diverse contexts to advocate for positive change at multiple levels. It is our view that being embedded and long term offers opportunities in terms of deep institutional and contextual knowledge, existing relationships and access to a wide range of stakeholders. Being networked offers opportunities to draw upon a wide range of expertise and perspectives, and to bring together internal and external insights (i.e.drawing on different positionalities). Long term funding means that the people and resources are in place and ready to respond in a timely way. However, many tensions and challenges remain, including difficulties in negotiating power and politics in the roles that researchers and research institutions can and should play in an emergency, and the position of empirical ethics within research programmes. We discuss some of these tensions and challenges and consider the implications for our own and similar networks in future.

Always leave the audience wanting more: An entertaining approach to stimulate engagement with health research among publics in coastal Kenya through 'Magnet Theatre'.

Background: Magnet Theatre (MT), a form of participatory community theatre, is one of several public engagement approaches used to facilitate engagement between KEMRI-Wellcome Trust Research Programme (KWTRP) researchers and public audiences in Coastal Kenya. We describe how we used MT as an entertaining forum where audiences learn about research, and where researchers learn about how the public views research. Methods: Drama scripts depicting community interaction with different aspects of research were developed iteratively with research staff, a theatre company and community members. Six fortnightly theatre outreaches per site over two months, attracting a total of 1454 audience members were held in Mida, a rural village 30 km north of Kilifi; and in Mtwapa, a peri-urban town 45 km to the south. Audiences were presented with dramatized health research-related dilemmas and subsequently invited to enact their responses. Evaluation comprised, notes and observations from meetings, rehearsals and outreaches, transcripts from a review workshop with repeat audience members (n=21), a reflection meeting with KWTRP engagement staff (n=12), and a group discussion with the theatre company (n=9). Discussions were recorded, transcribed, translated to English and analysed using thematic approach. Results: Despite being costly in terms of time and expense, we argue that MT in public spaces can assist audience members to navigate 'border-crossings' between everyday contexts and scientific/research concepts. This can enable audiences to share their views and concerns and enact their responses to research-related dilemmas. Conclusions: While reporting on MT's successes, drawing from literature on rumours, we acknowledge the limitations of individual engagement activities in providing long-term solutions to address alternative interpretations and rumours about research, in the context of local and global inequities. MT, however, presents an opportunity for researchers to express respect to public audiences through making research more accessible and providing opportunities to listen to public views and concerns.

Understanding the benefits and burdens associated with a malaria human infection study in Kenya: experiences of study volunteers and other stakeholders.

BACKGROUND: Human infection studies (HIS) that involve deliberately infecting healthy volunteers with a pathogen raise important ethical issues, including the need to ensure that benefits and burdens are understood and appropriately accounted for. Building on earlier work, we embedded social science research within an ongoing malaria human infection study in coastal Kenya to understand the study benefits and burdens experienced by study stakeholders in this low-resource setting and assess the wider implications for future research planning and policy. METHODS: Data were collected using qualitative research methods, including in-depth interviews (44), focus group discussions (10) and non-participation observation. Study participants were purposively selected (key informant or maximal diversity sampling), including volunteers in the human infection study, study staff, community representatives and local administrative authorities. Data were collected during and up to 18 months following study residency, from sites in Coastal and Western Kenya. Voice recordings of interviews and discussions were transcribed, translated, and analysed using framework analysis, combining data- and theory-driven perspectives. FINDINGS: Physical, psychological, economic and social forms of benefits and burdens were experienced across study stages. Important benefits for volunteers included the study compensation, access to health checks, good residential living conditions, new learning opportunities, developing friendships and satisfaction at contributing towards a new malaria vaccine. Burdens primarily affected study volunteers, including experiences of discomfort and ill health; fear and anxiety around aspects of the trial process, particularly deliberate infection and the implications of prolonged residency; anxieties about early residency exit; and interpersonal conflict. These issues had important implications for volunteers' families, study staff and the research institution's reputation more widely. CONCLUSION: Developing ethically and scientifically strong HIS relies on grounded accounts of volunteers, study staff and the wider community, understood in the socioeconomic, political and cultural context where studies are implemented. Recognition of the diverse, and sometimes perverse, nature of potential benefits and burdens in a given context, and who this might implicate, is critical to this process. Prior and ongoing stakeholder engagement is core to developing these insights.

A scoping review of considerations and practices for benefit sharing in biobanking.

BACKGROUND: Despite the rapid global growth of biobanking over the last few decades, and their potential for the advancement of health research, considerations specific to the sharing of benefits that accrue from biobanks have received little attention. Questions such as the types and range of benefits that can arise in biobanking, who should be entitled to those benefits, when they should be provided, by whom and in what form remain mostly unanswered. We conducted a scoping review to describe benefit sharing considerations and practices in biobanking in order to inform current and future policy and practice. METHODS: Drawing on the Arksey and O'Malley framework, we conducted a scoping review of the literature in three online databases (PubMed, Cochrane library, and Google Scholar). We extracted and charted data to capture general characteristics, definitions and examples of benefits and benefit sharing, justification for benefit sharing, challenges in benefit sharing, governance mechanisms as well as proposed benefit sharing mechanisms. RESULTS: 29 articles published between 1999 and 2020 met the inclusion criteria for the study. The articles included 5 empirical and 24 non-empirical studies. Only 12 articles discussed benefit sharing as a stand-alone subject, while the remaining 17 integrated a discussion of benefits as one issue amongst others. Major benefit sharing challenges in biobanking were found to be those associated with uncertainties around the future use of samples and in resultant benefits. CONCLUSION: Most of the benefit sharing definitions and approaches currently in use for biobanking are similar to those used in health research. These approaches may not recognise the distinct features of biobanking, specifically relating to uncertainties associated with the sharing and re-use of samples. We therefore support approaches that allow decisions about benefit sharing to be made progressively once it is apparent who samples are to be shared with, the intended purpose and expected benefits. We also highlight gaps in key areas informing benefit sharing in biobanking and draw attention to the need for further empirical research.

The Essential Role of Data and Safety Monitoring Boards (DSMBs) in Ensuring the Ethics of Global Vaccine Trials to Address Coronavirus Disease 2019 (COVID-19O).

Coronavirus disease 2019 (COVID-19) vaccines are being developed and implemented with unprecedented speed. Accordingly, trials considered ethical at their inception may quickly become concerning. We provide recommendations for Data and Safety Monitoring Boards (DSMBs) on monitoring the ethical acceptability of COVID-19 vaccine trials, focusing on placebo-controlled trials in low- and middle-income countries.

The Africa Ethics Working Group (AEWG): a model of collaboration for psychiatric genomic research in Africa.

The Africa Ethics Working Group (AEWG) is a South-South-North collaboration of bioethics and mental health researchers from sub-Saharan Africa, working to tackle emerging ethical challenges in global mental health research. Initially formed to provide ethical guidance for a neuro-psychiatric genomics research project, AEWG has evolved to address cross cutting ethical issues in mental health research aimed at addressing equity in North-South collaborations. Global South refers to economically developing countries (sub-Saharan Africa in this context) and Global North to economically developed countries (primarily Europe, UK and North America). In this letter we discuss lessons that as a group we have learnt over the last three years; lessons that similar collaborations could draw on. With increasing expertise from Global South as an outcome of several capacity strengthening initiatives, it is expected that the nature of scientific collaborations will shift to a truly equitable partnership. The AEWG provides a model to rethink contributions that each partner could make in these collaborations.