Parental Perspectives Regarding the Return of Genomic Research Results in Neurodevelopmental Disorders in South Africa: Anticipated Impact and Preferences.

Few policies and little research exist regarding the disclosure of genomic results to research participants in Africa. As understanding participant preferences would be pivotal to the success of the feedback process, this study set out to address this issue by engaging with enrolled participants from an ongoing genomics research project on neurodevelopmental disorders with the aim to assess the anticipated impact of receiving pertinent results and explore the preferences for feedback in a South-African context. Twelve semi-structured interviews were conducted with 17 parents of children participating in the research study. Transcribed interview data and observational notes were analysed using thematic analysis and framework matrices. Participants linked their own meaning to the impact of receiving a pertinent result and perceived the information as useful for reasons other than only clinical utility. These included closure, improved management of their child's condition and information regarding recurrence risks. In terms of preferences for feedback, an in-person result delivery session, conducted by a member of the study team or medical professional familiar with their child was preferred. In addition, participants felt a sense of ownership over their blood or their contribution to the research study, finding meaning even in non-pertinent (secondary findings) or negative results. These findings provide insight into the type of discussions that may be valuable in enabling the development of best practices and guidelines for the return of individual genetic research results, in a culturally appropriate manner, within South-African communities.

Perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research.

BACKGROUND: Genetic research can yield information that is unrelated to the study's objectives but may be of clinical or personal interest to study participants. There is an emerging but controversial responsibility to return some genetic research results, however there is little evidence available about the views of genomic researchers and others on the African continent. METHODS: We conducted a continental survey to solicit perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research. RESULTS: A total of 110 persons participated in the survey with 51 complete and 59 incomplete surveys received. Data was summarised using descriptive analysis. Overall, our respondents believed that individual genetic research results that are clinically actionable should be returned to study participants apparently because participants have a right to know things about their health, and it might also be a means for research participation to be recognized. Nonetheless, there is a need for development of precise guidance on how to return individual genetic research findings in African genomics research. DISCUSSION: Participants should receive information that could promote a healthier lifestyle; only clinically actionable findings should be returned, and participants should receive all important information that is directly relevant to their health. Nevertheless, detailed guidelines should inform what ought to be returned. H3Africa guidelines stipulate that it is generally considered good practice for researchers to feedback general study results, but there is no consensus about whether individual genomic study results should also be fed back. The decision on what individual results to feedback, if any, is very challenging and the specific context is important to make an appropriate determination.

Enhancing Reciprocity, Equity and Quality of Ethics Review for Multisite Research During Public Health Crises: The Experience of the COVID-19 Clinical Research Coalition Ethics Working Group.

In this paper we report findings from a commissioned report to the COVID-19 Clinical Research Coalition on approaches to streamline multinational REC review/approval during public health emergencies. As currently envisioned in the literature, a system of REC mutual recognition is theoretically possible based on shared procedural REC standards, but raises numerous concerns about perceived inequities and mistrust.

Lessons learned from the translation of the Internalised Stigma of Mental Illness (ISMI) scale into isiXhosa for use with South African Xhosa people with schizophrenia.

Internalised stigma is highly prevalent among people with mental illness. This is concerning because internalised stigma is often associated with negative consequences affecting individuals' personal, familial, social, and overall wellbeing, employment opportunities and recovery. Currently, there is no psychometrically validated instrument to measure internalised stigma among Xhosa people in their home language. Our study aimed to translate the Internalised Stigma of Mental Illness (ISMI) scale into isiXhosa. Following WHO guidelines, the ISMI scale was translated using a five-stage translation design which included (i) forward-translation, (ii) back-translation, (iii) committee approach, (iv) quantitative piloting, and (v) qualitative piloting using cognitive interviews. The ISMI isiXhosa version (ISMI-X) underwent psychometric testing to establish utility, within-scale validity, convergent, divergent, and content validity (assessed using frequency of endorsements and cognitive interviewing) with n = 65 Xhosa people with schizophrenia. The resultant ISMI-X scale demonstrated good psychometric utility, internal consistency for the overall scale (α = .90) and most subscales (α > .70, except the Stigma Resistance subscale where α = .57), convergent validity between the ISMI Discrimination Experiences subscale and the Discrimination and Stigma (DISC) scale's Treated Unfairly subscale (r = .34, p = .03) and divergent validity between the ISMI Stigma Resistance and DISC Treated Unfairly subscales (r = .13, p = .49). But more importantly the study provides valuable insights into strengths and limitations of the present translation design. Specifically, validation methods such as assessing frequency of endorsements of scale items and using cognitive interviewing to establish conceptual clarity and relevance of items may be useful in small piloting sample sizes.

Feeding back of individual genetic results in Botswana: mapping opportunities and challenges.

PURPOSE: We explored the views of Botswana stakeholders involved in developing, implementing and applying ethical standards for return of individual study results from genomic research. This allowed for mapping opportunities and challenges regarding actionability requirements that determine whether individual genomic research results should be fed back. METHODS: Using in-depth interviews, this study explored the views of sixteen (16) stakeholders about the extent, nature and timing of feedback of individual genomic research findings, including incidental findings that arise in the context of African genomics research. Coded data was analyzed through an iterative process of analytic induction to document and interpret themes. RESULTS: Overall, respondents were of the view that feedback of actionable individual genomic results was an important outcome that could benefit participants. However, a number of themes surfaced that pointed to opportunities and challenges that exist in Botswana that could help in planning for feeding back of individual genomic results that were mapped. Some of the opportunities cited by the respondents included the existence of good governance; democracy and humanitarianism; universal healthcare system; national commitment to science; research and innovation to transform Botswana into a knowledge-based economy; and applicable standard of care which could promote actionability. On the other hand, contextual issues like the requirement for validation of genomic research results in accredited laboratories, high cost of validation of genomic results, and linkage to care, as well as lack of experts like genomic scientists and counselors were considered as challenges for return of individual results. CONCLUSION: We propose that decisions whether and which genomic results to return take into consideration contextual opportunities and challenges for actionability for return of results in a research setting. This is likely to avoid or minimize ethical issues of justice, equity and harm regarding actionability decisions.

Participant views on practical considerations for feedback of individual genetic research results: a case study from Botswana.

Key to discussions around feedback of individual results from genomics research are practical questions on how such results should be fed back, by who and when. However, there has been virtually no work investigating these practical considerations for feedback of individual genetic results in the context of low-and middle-income countries (LMICs), especially in Africa. Consequently, we conducted deliberative focus group discussions with 6 groups of adolescents (n = 44) who previously participated in a genomics study in Botswana as well as 6 groups of parents and caregivers (n = 49) of children who participated in the same study. We also conducted in-depth interviews with 6 adolescents and 6 parents or caregivers. Our findings revealed that both adolescents and parents would prefer to receive their individual genetic results in person, with adolescents preferring researchers to provide feedback, while parents preferred doctors who are associated with the study. Both adolescents and parents further expressed that feedback should be supported by counselling but differed on the timing of feedback, with preferences ranging from feedback as quickly as possible to feedback at project end. In conclusion, decisions on practicalities for feedback of results should be done in account of participants' context and considerations of participants' preferences.

Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa.

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.

Where is knowledge from the global South? An account of epistemic justice for a global bioethics.

The silencing of the epistemologies, theories, principles, values, concepts and experiences of the global South constitutes a particularly egregious epistemic injustice in bioethics. Our shared responsibility to rectify that injustice should be at the top of the ethics agenda. That it is not, or only is in part, is deeply problematic and endangers the credibility of the entire field. As a first step towards reorienting the field, this paper offers a comprehensive account of epistemic justice for global health ethics. We first introduce several different conceptions of justice and decolonisation in relation to knowledge, purposefully drawing on work emanating from the global South as well as the global North. We then apply those conceptions to the global health ethics context to generate a tripartite account of the layers of epistemic justice in the field: who is producing ethics knowledge; what theories and concepts are being applied to produce ethics knowledge; and whose voices are sought, recorded and used to generate ethics knowledge. These layers reflect that the field spans conceptual and empirical research. We conclude by proposing that, going forward, three avenues are key to achieve greater epistemic justice at each layer and to help decolonise global health ethics: namely, understanding the problem, dialogue and structural change.

Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

BACKGROUND: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. METHODS: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. RESULTS: Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. CONCLUSIONS: RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

Addressing exploitation and inequities in open science: A relational perspective.

There are concerns that participation in open science will lead to various forms of exploitation - of researchers and scholars in low-income countries and under-resourced institutions. This article defends a contrary thesis and demonstrates the exact ways the underexplored notions of communal relationships, human dignity and social justice - and the normative principles to which they give rise - grounded in African philosophy can usefully address critical concerns regarding exploitation in the sharing of research resources to facilitate open partnership/collaboration and reuse. Further research is required to study the specific roles different institutions can play in facilitating open practice and contribute towards establishing effective structures that can enhance equity and balance unfavourable power asymmetries.

Epistemic justice, African values and feedback of findings in African genomics research.

This article draws on key normative principles grounded in important values - solidarity, partiality and friendliness - in African philosophy to think critically and deeply about the ethical challenges around returning individual genetic research findings in African genomics research. Precisely, we propose that the normative implication of solidarity, partiality and friendliness is that returning findings should be considered as a gesture of goodwill to participants to the extent that it constitutes acting for their well-being. Concretely, the value of friendliness may imply that one ought to return actionable results to participants even when their preferences regarding feedback are unknown. Notwithstanding, returning individual genetic results will have a cost implication. The cost of feeding back is relevant in the context of African genomics research projects, which are often funded by international sponsors and should be researched further.

Whole Exome Sequencing in South Africa: Stakeholder Views on Return of Individual Research Results and Incidental Findings.

The use of whole exome sequencing (WES) in medical research is increasing in South Africa (SA), raising important questions about whether and which individual genetic research results, particularly incidental findings, should be returned to patients. Whilst some commentaries and opinions related to the topic have been published in SA, there is no qualitative data on the views of professional stakeholders on this topic. Seventeen participants including clinicians, genomics researchers, and genetic counsellors (GCs) were recruited from the Western Cape in SA. Semi-structured interviews were conducted, and the transcripts analysed using the framework approach for data analysis. Current roadblocks for the clinical adoption of WES in SA include a lack of standardised guidelines; complexities relating to variant interpretation due to lack of functional studies and underrepresentation of people of African ancestry in the reference genome, population and variant databases; lack of resources and skilled personnel for variant confirmation and follow-up. Suggestions to overcome these barriers include obtaining funding and buy-in from the private and public sectors and medical insurance companies; the generation of a locally relevant reference genome; training of health professionals in the field of genomics and bioinformatics; and multidisciplinary collaboration. Participants emphasised the importance of upscaling the accessibility to and training of GCs, as well as upskilling of clinicians and genetic nurses for return of genetic data in collaboration with GCs and medical geneticists. Future research could focus on exploring the development of stakeholder partnerships for increased access to trained specialists as well as community engagement and education, alongside the development of guidelines for result disclosure.

Should institutions fund the feedback of individual findings in genomic research?

The article argues the thesis that institutions have a prima facie obligation to fund the feedback of individual findings in genomic research conducted on the African continent by drawing arguments from an underexplored Afro-communitarian view of distributive justice and rights of researchers to be aided. Whilst some studies have explored how institutions have a duty to support return as a form of ancillary care or additional foreseeable service in research by mostly appealing to dominant principles and theories in the Global North, this mostly normative study explores this question by appealing to underexplored African philosophy. This is a new way of thinking about institutional responsibility to fund feedback and responds to the call to decolonise health research in Africa. Further studies are required to study how this prima facie obligation will interact with social contexts and an institution's extant relationships to find an actual duty. The research community should also work out procedures, policies and governance structures to facilitate feedback. In our opinion, though the impacts of feeding back can inform how institutions think about their actual duty, these do not obliterate the binding duty to fund feedback.

Considerations of Autonomy in Guiding Decisions around the Feedback of Individual Genetic Research Results from Genomics Research: Expectations of and Preferences from Researchers in Botswana.

Background: The Human Health and Heredity (H3Africa) Consortium continues to generate large amounts of genomic data leading to new insights into health and disease among African populations. This has however generated debate among stakeholders involved in developing, implementing, and applying ethical standards and policies for the return of individual genetic research results. The key questions are about when results must, should, may, or must not be returned and by whom. This study aimed to explore the views on the feedback of individual pertinent and incidental genetic research results of researchers, ethics committee members, and policymakers in Botswana. Methods: In-depth interviews were conducted with 16 key stakeholders from academic, research institutions, and regulatory bodies in Botswana. An analysis of the coded data was done through an iterative process of analytic induction to document and interpret themes and patterns. Results: Overall, the study indicated that researchers have at least a partial obligation to return individual genetic research results to research participants. Respondents placed emphasis on the ethical principle of autonomy. They felt that it was inappropriate for researchers to make decisions about the return of results on participants' behalf except in situations of avoiding participant self-harm or harm to society. Conclusion: Findings helped to highlight the importance of considering participants' autonomy in the development of sustainable and credible guidelines for feedback of findings from genomics research in Botswana, which can be explained during community engagement and consent processes. Such guidelines would ultimately be used to develop policies, guide African genomics research, and promote participant autonomy, transparency, and possibly participant trust in research.

Guideline for feedback of individual genetic research findings for genomics research in Africa.

As human genomics research in Africa continues to generate large amounts of data, ethical issues arise regarding how actionable genetic information is shared with research participants. The Human Heredity and Health in Africa Consortium (H3Africa) Ethics and Community Engagement Working group acknowledged the need for such guidance, identified key issues and principles relevant to genomics research in Africa and developed a practical guideline for consideration of feeding back individual genetic results of health importance in African research projects. This included a decision flowchart, providing a logical framework to assist in decision-making and planning for human genomics research projects. Although presented in the context of the H3Africa Consortium, we believe the principles described, and the decision flowchart presented here is applicable more broadly in African genomics research.