An Ethical Framework for Research Using Genetic Ancestry.

A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications. This essay presents an ethics framework in the spirit of virtue ethics for these researchers: rather than focus on rule following, the framework is designed to build researchers' capacities to react to the ethical dimensions of their work. The authors identify one overarching principle of intellectual freedom and responsibility, noting that freedom in all its guises comes with responsibility, and they identify and define four principles that collectively uphold researchers' intellectual responsibility: truthfulness, justice and fairness, anti-racism, and public beneficence. Researchers should bring their practices into alignment with these principles, and to aid this, the authors name three common ways research practices infringe these principles, suggest a step-by-step process for aligning research choices with the principles, provide rules of thumb for achieving alignment, and give a worked case. The essay concludes by identifying support needed by researchers to act in accord with the proposed framework.

Ancestry: How researchers use it and what they mean by it.

Background: Ancestry is often viewed as a more objective and less objectionable population descriptor than race or ethnicity. Perhaps reflecting this, usage of the term "ancestry" is rapidly growing in genetics research, with ancestry groups referenced in many situations. The appropriate usage of population descriptors in genetics research is an ongoing source of debate. Sound normative guidance should rest on an empirical understanding of current usage; in the case of ancestry, questions about how researchers use the concept, and what they mean by it, remain unanswered. Methods: Systematic literature analysis of 205 articles at least tangentially related to human health from diverse disciplines that use the concept of ancestry, and semi-structured interviews with 44 lead authors of some of those articles. Results: Ancestry is relied on to structure research questions and key methodological approaches. Yet researchers struggle to define it, and/or offer diverse definitions. For some ancestry is a genetic concept, but for many-including geneticists-ancestry is only tangentially related to genetics. For some interviewees, ancestry is explicitly equated to ethnicity; for others it is explicitly distanced from it. Ancestry is operationalized using multiple data types (including genetic variation and self-reported identities), though for a large fraction of articles (26%) it is impossible to tell which data types were used. Across the literature and interviews there is no consistent understanding of how ancestry relates to genetic concepts (including genetic ancestry and population structure), nor how these genetic concepts relate to each other. Beyond this conceptual confusion, practices related to summarizing patterns of genetic variation often rest on uninterrogated conventions. Continental labels are by far the most common type of label applied to ancestry groups. We observed many instances of slippage between reference to ancestry groups and racial groups. Conclusion: Ancestry is in practice a highly ambiguous concept, and far from an objective counterpart to race or ethnicity. It is not uniquely a "biological" construct, and it does not represent a "safe haven" for researchers seeking to avoid evoking race or ethnicity in their work. Distinguishing genetic ancestry from ancestry more broadly will be a necessary part of providing conceptual clarity.

"By only considering the end product it means that our participation has always been in vain": Defining benefits in HIV vaccine trials in Tanzania.

Debates about what constitutes benefits in human research continue to be less informed due to a lack of empirical evidence from the developing world. This study aimed to explore what constitutes benefits in HIV vaccine trials in Tanzania and examine inherent ethical implications. A qualitative case study design was deployed and a total of 29 purposively selected study participants comprising of experienced researchers, institutional review board members and community advisory board members were included. Collected data were analyzed by thematic analysis aided by computer software: MAXQDA version 20.4.0. The study findings indicate that there is a growing appreciation of benefits beyond actual vaccines to include 1) capacity building at individual, community, institutional and regulatory levels; and 2) non-capacity building related benefits such as strengthened collaborations, ancillary care and employment opportunities. So, as the struggle for viable HIV vaccines continues, other benefits that have accrued from such trials are not to be blindsided especially for developing countries like Tanzania.

A scoping review of guidelines for the use of race, ethnicity, and ancestry reveals widespread consensus but also points of ongoing disagreement.

The use of population descriptors such as race, ethnicity, and ancestry in science, medicine, and public health has a long, complicated, and at times dark history, particularly for genetics, given the field's perceived importance for understanding between-group differences. The historical and potential harms that come with irresponsible use of these categories suggests a clear need for definitive guidance about when and how they can be used appropriately. However, while many prior authors have provided such guidance, no established consensus exists, and the extant literature has not been examined for implied consensus and sources of disagreement. Here, we present the results of a scoping review of published normative recommendations regarding the use of population categories, particularly in genetics research. Following PRISMA guidelines, we extracted recommendations from n = 121 articles matching inclusion criteria. Articles were published consistently throughout the time period examined and in a broad range of journals, demonstrating an ongoing and interdisciplinary perceived need for guidance. Examined recommendations fall under one of eight themes identified during analysis. Seven are characterized by broad agreement across articles; one, "appropriate definitions of population categories and contexts for use," revealed substantial fundamental disagreement among articles. Additionally, while many articles focus on the inappropriate use of race, none fundamentally problematize ancestry. This work can be a resource to researchers looking for normative guidance on the use of population descriptors and can orient authors of future guidelines to this complex field, thereby contributing to the development of more effective future guidelines for genetics research.

Getting genetic ancestry right for science and society.

We must embrace a multidimensional, continuous view of ancestry and move away from continental ancestry categories.

Breast cancer screening in sub-Saharan Africa: a systematic review and ethical appraisal.

BACKGROUND: The aim of this systematic review was to evaluate the evidence and clinical outcomes of screening interventions and implementation trials in sub-Saharan Africa (SSA) and also appraise some ethical issues related to screening in the region through quantitative and qualitative narrative synthesis of the literature. METHODS: We searched Pubmed, OvidMEDLINE, Embase, and Web of Science to identify studies published on breast cancer screening interventions and outcomes in SSA. Descriptive statistics were used to summarize the frequency and proportions of extracted variables, and narrative syntheses was used to evaluate the clinical outcomes of the different screening modalities. The mixed methods appraisal tool was used to assess the quality of studies included in the review. RESULTS: Fifteen studies were included, which consisted of 72,572 women in ten countries in SSA. 63% (8/15) of the included publications evaluated Clinical Breast Examination (CBE), 47% (7/15) evaluated mammography and 7% (1/15) evaluated ultrasound screening. The cancer detection rate was < 1/1000 to 3.3/1000 and 3.3/100 to 56/1000 for CBE and mammography screening respectively. There was a lot of heterogeneity in CBE methods, target age for screening and no clear documentation of screening interval. Cost-effective analyses showed that CBE screening linked to comprehensive cancer care is most cost effective. There was limited discussion of the ethics of screening, including the possible harms of screening in the absence of linkage to care. The gap between conducting good screening program and the appropriate follow-up with diagnosis and treatment remains one of the major challenges of screening in SSA. DISCUSSION: There is insufficient real-world data to support the systematic implementation of national breast cancer screening in SSA. Further research is needed to answer important questions about screening, and national and international partnerships are needed to ensure that appropriate diagnostic and treatment modalities are available to patients who screen positive.

The benefit sharing vision of H3Africa.

One of the central ethical tenets of research in developing countries is the sponsor's obligation to benefit host participants and communities. Two known models of benefits provision dominate the ethical discourse of research in developing countries. The first model, known as the "reasonable availability," endorses the obligation to provide interventions proven to be effective at the end of a study. This contrasts with the second model, known as "fair benefits," which endorses other forms of benefits that host communities may deem as fair beyond those derived directly from the study's findings. This paper explores a third benefit model consistent with the writings of the Human Hereditary and Health in Africa (H3Africa) research initiative. The H3Africa-a North-South collaborative initiative predicated by U.S. National Institutes of Health, the Wellcome Trust and the African Society of Human Genetics upholds a benefit model that endorses capacity building as the primary obligation of its research agenda. This is evident by the endorsement of mechanisms to strengthen capacity building in its research projects. While capacity building remains a plausible means of improving the expertise, quality and independence of research in Africa, sustainable measures are needed to realizing the full potential for African-led research on the continent.

Viewing benefit sharing in global health research through the lens of Aristotelian justice.

The ethics of benefit sharing has been a topical issue in global health research in resource-limited countries. It pertains to the distribution of goods, benefits and advantages to the research participants, communities and countries that are involved in research. One of the nuances in benefit sharing is the ethical justification on which the concept should be based. Extensive literature outlining the different principles underlying benefit sharing is available. The purpose of this paper is to examine the proposed principles using Aristotelian principles of justice. The paper assesses the central idea of Aristotelian justice and applies and evaluates this idea to benefit sharing in research, especially when commercial research sponsors conduct research in resource-limited countries. Two categories of Aristotelian justice-universal and particular-were examined and their contribution to the benefit-sharing discourse assessed. On the one hand, benefit sharing in accordance with universal justice requires that for-profit research sponsors obey the legal regulations and international standards set for benefit sharing. On the other hand, benefit sharing in accordance with particular justice transcends obeying legal requirements and standards to a realm of acting in an ethically accepted manner. Accordingly, the paper further examines three perspectives of particular justice and develops ethical justification for benefit sharing in global health research. As Aristotelian justice is still relevant to the contemporary discourse on justice, this paper broadens the ethical justifications of benefit sharing in global health research.

What Do the Various Principles of Justice Mean Within the Concept of Benefit Sharing?

The concept of benefit sharing pertains to the act of giving something in return to the participants, communities, and the country that have participated in global health research or bioprospecting activities. One of the key concerns of benefit sharing is the ethical justifications or reasons to support the practice of the concept in global health research and bioprospecting. This article evaluates one of such ethical justifications and its meaning to benefit sharing, namely justice. We conducted a systematic review to map the various principles of justice that are linked to benefit sharing and analysed their meaning to the concept of benefit sharing. Five principles of justice (commutative, distributive, global, procedural, and compensatory) have been shown to be relevant in the nuances of benefit sharing in both global health research and bioprospecting. The review findings indicate that each of these principles of justice provides a different perspective for a different benefit sharing rationale. For example, commutative justice provides a benefit sharing rationale that is focused on fair exchange of benefits between research sponsors and communities. Distributive justice produces a benefit sharing rationale that is focused on improving the health needs of the vulnerable research communities. We have suggested that a good benefit sharing framework particularly in global health research would be more beneficial if it combines all the principles of justice in its formulation. Nonetheless, there is a need for empirical studies to examine the various principles of justice and their nuances in benefit sharing among stakeholders in global health research.

Benefit sharing: an exploration on the contextual discourse of a changing concept.

BACKGROUND: The concept of benefit sharing has been a topical issue on the international stage for more than two decades, gaining prominence in international law, research ethics and political philosophy. In spite of this prominence, the concept of benefit sharing is not devoid of controversies related to its definition and justification. This article examines the discourses and justifications of benefit sharing concept. DISCUSSION: We examine the discourse on benefit sharing within three main spheres; namely: common heritage of humankind, access and use of genetic resources according to the Convention on Biological Diversity (CBD), and international clinical research. Benefit sharing has changed from a concept that is enshrined in a legally binding regulation in the contexts of common heritage of humankind and CBD to a non-binding regulation in international clinical research. Nonetheless, there are more ethical justifications that accentuate benefit sharing in international clinical research than in the contexts of common heritage of humankind and the CBD. SUMMARY: There is a need to develop a legal framework in order to strengthen the advocacy and decisiveness of benefit sharing practice in international health research. Based on this legal framework, research sponsors would be required to provide a minimum set of possible benefits to participants and communities in research. Such legal framework on benefit sharing will encourage research collaboration with local communities; and dispel mistrust between research sponsors and host communities. However, more research is needed, drawing from other international legal frameworks, to understand how such a legal framework on benefit sharing can be successfully formulated in international health research.