Rethinking Benefit and Responsibility in the Context of Diversity: Perspectives from the Front Lines of Precision Medicine Research.

INTRODUCTION: Federal agencies have instituted guidelines to prioritize the enrollment and retention of diverse participants in precision medicine research (PMR). Prior studies examining participation of minoritized communities have shown that potential benefits represent a key determinant. Human subject research guidance, however, conceptualizes potential benefits narrowly, emphasizing generalized advances in medical knowledge. Further, few studies have provided qualitative data that critically examine how the concept of "benefit" is interpreted or challenged in the context of research practice. This paper examines the experiences of PMR investigators and frontline research staff to understand how standard approaches to benefit are received, contested, and negotiated "on the ground." METHODS: Findings are drawn from a qualitative project conducted across five US-based, federally funded PMR studies. Data collection included 125 in-depth interviews with a purposive sample of investigators, research staff, community advisory board members, and NIH program officers associated with these PMR studies. RESULTS: Researchers report that the standard approach to benefit - which relies on the premise of altruism and the promise of incrementally advancing scientific knowledge - is frequently contested. Researchers experience moral distress over the unmet clinical, psychosocial, and material needs within the communities they are engaging. Many believe the broader research enterprise has a responsibility to better address these needs. CONCLUSION: Researchers frequently take issue with and sometimes negotiate what is owed to participants and to their communities in exchange for the data they provide. These experiences of moral distress and these improvisations warrant systematic redress, not by individual researchers but by the broader research ethics infrastructure.

Community Engagement in Precision Medicine Research: Organizational Practices and Their Impacts for Equity.

BACKGROUND: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal. METHODS: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for. RESULTS: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. Critical differences emerged when engagement and research decisionmaking were integrated with each other versus occurring in parallel, separate parts of the study organization, and whether community members had the ability to determine which issues would be brought to them for consideration or to revise or even veto proposals made upstream based on criteria that mattered to them. CE was understood to have a range of purposes, from instrumentally facilitating recruitment and data collection, to advancing community priorities and concerns, to furthering long-term investments in relationships with and changes in communities. These choices about who to engage, what engagement activities to support, how to solicit and integrate community input into the workflow of the study, and what CE was for were often conditioned upon preexisting perceptions and upstream decisions about study goals, competing priorities, and resource availability. CONCLUSIONS: Upstream choices about CE and constraints of time and resources cascade into tradeoffs that often culminated in "pantomime community engagement." This approach can create downstream costs when engagement is experienced as improvised and sporadic. Transformations are needed for CE to be seen as a necessary scientific investment and part of the scientific process.

Co-Harboring of Beta-Lactamases and mcr-1 Genes in Escherichia coli and Klebsiella pneumoniae from Healthy Carriers and Backyard Animals in Rural Communities in Ecuador.

Few studies have addressed drug resistance of Enterobacterales in rural communities in developing countries. This study aimed to determine the coexistence of extended-spectrum ß-lactamase (ESBL) and carbapenemase genes in Escherichia coli and Klebsiella pneumoniae strains carrying the mcr-1 gene in rural communities in Ecuador from healthy humans and their backyard animals. Sixty-two strains, thirty E. coli and thirty-two K. pneumoniae strains carrying the mcr-1 gene were selected from a previous study. PCR were performed for the presence of ESBLs and carbapenemase genes. The strains were further characterized, and the genetic relationship was studied with multi-locus sequencing typing (MLST) of seven housekeeping genes. Fifty-nine of the sixty-two mcr-1 isolates (95%) harbored at least on ß-lactam resistance gene. The most prevalent ESBL genes were the blaTEM genes (present in in 80% of the E. coli strains) and the blaSHV gene (present in 84% of the K. pneumoniae strains). MSLT analysis revealed 28 different sequence types (ST); 15 for E. coli and 12 for K. pneumoniae, with most ST never described in humans and animals. The coexistence of mcr-1 and ß-lactams resistant genes in E. coli and K. pneumoniae strains is alarming and threatens the efficacy of last-resort antibiotics. Our findings highlight backyard animals as a reservoir of mcr-1/ß-lactams resistant genes.

Diversity and prevalence of gastrointestinal helminths of free-roaming dogs on coastal beaches in Ecuador: Potential for zoonotic transmission.

Free-roaming dogs are highly exposed to a range of zoonotic parasites, including helminths, which can be transmitted to humans, particularly in rural tropical settings of developing countries. To evidence the diversity and prevalence of gastrointestinal helminths in the stools of free-roaming dogs on the public Pacific coastal beaches of Ecuador, a cross-sectional study was conducted from August 2021 to August 2022. The sampling beaches are located along the tropical Pacific coastal region. Stools were collected from the ground in containers with 10% formalin and processed using the Ritchie method; eggs were identified under a microscope. A total of 573 stools were examined from 20 beaches; the overall prevalence was 157 (27.4%) for one or more helminths. Ten parasites were identified, nine of which are potentially zoonotic. Ancylostoma spp. was the most prevalent (19.4%), followed by Toxocara spp. (7.2%). Trichuris spp., Dipylidium caninum, Diphyllobothrium spp., Capillaria spp., Dicrocoelium spp., Heterobilharzia americana, Hymenolepis spp. and Spirocerca spp. were also observed. Five of them are reported for the first-time infecting dogs in Ecuador. Hence, we evidenced that Ecuadorian beaches are highly contaminated with the dogs' zoonotic gastrointestinal helminths, posing a great risk to public health. Differences in the presence and prevalence were found in samples of tropical humid and dry climate zones. Therefore, based on our findings, we encourage the implementation of broad antiparasitic treatment and prevention strategies to reduce the zoonotic risk.

Targeting Representation: Interpreting Calls for Diversity in Precision Medicine Research.

Scientists have identified a "diversity gap" in genetic samples and health data, which have been drawn predominantly from individuals of European ancestry, as posing an existential threat to the promise of precision medicine. Inadequate inclusion as articulated by scientists, policymakers, and ethicists has prompted large-scale initiatives aimed at recruiting populations historically underrepresented in biomedical research. Despite explicit calls to increase diversity, the meaning of diversity - which dimensions matter for what outcomes and why - remain strikingly imprecise. Drawing on our document review and qualitative data from observations and interviews of funders and research teams involved in five precision medicine research (PMR) projects, we note that calls for increasing diversity often focus on "representation" as the goal of recruitment. The language of representation is used flexibly to refer to two objectives: achieving sufficient genetic variation across populations and including historically disenfranchised groups in research. We argue that these dual understandings of representation are more than rhetorical slippage, but rather allow for the contemporary collection of samples and data from marginalized populations to stand in as correcting historical exclusion of social groups towards addressing health inequity. We trace the unresolved historical debates over how and to what extent researchers should procure diversity in PMR and how they contributed to ongoing uncertainty about what axes of diversity matter and why. We argue that ambiguity in the meaning of representation at the outset of a study contributes to a lack of clear conceptualization of diversity downstream throughout subsequent phases of the study.

Strategies of inclusion: The tradeoffs of pursuing "baked in" diversity through place-based recruitment.

US funding agencies have begun to institutionalize expectations that biomedical studies achieve defined thresholds for diversity among research participants, including in precision medicine research (PMR). In this paper, we examine how practices of recruitment have unfolded in the wake of these diversity mandates. We find that a very common approach to seeking diverse participants leverages understandings of spatial, geographic, and site diversity as proxies and access points for participant diversity. That is, PMR investigators recruit from a diverse sampling of geographic areas, neighborhoods, sites, and institutional settings as both opportunistic but also meaningful ways to "bake in" participant diversity. In this way, logics of geographic and institutional diversity shift the question from who to recruit, to where. However, despite seeing geographic and site diversity as social and scientific 'goods' in the abstract and as key to getting diverse participants, PMR teams told us that working with diverse sites was often difficult in practice due to constraints in funding, time, and personnel, and inadequate research infrastructures and capacity. Thus, the ways in which these geographic and institutional diversity strategies were implemented resulted ultimately in limiting the meaningful inclusion of populations and organizations that had not previously participated in biomedical research and reproduced the inclusion of institutions that are already represented. These prevailing assumptions about and practices of "baked-in" diversity in fact exacerbate and produce other forms of inequity, in research capacity and research representation. These findings underscore how structural inequities in research resources must be addressed for diversity to be achieved in both research sites and research participants.

Beyond inclusion: Enacting team equity in precision medicine research.

PURPOSE: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams. METHODS: We conducted in-depth interviews with 102 individuals involved in three U.S.-based precision medicine research consortia and conducted over 400 observation hours of their working group meetings, consortium-wide meetings, and conference presentations. We also reviewed published reports on genomic workforce diversity (WFD), particularly those relevant to the PMR community. RESULTS: Our study finds that many PMR teams encounter challenges as they strive to achieve equitable diversification on scientific teams. Interviewees articulated that underrepresented team members were often hired to increase the study's capacity to recruit diverse research participants, but are limited to on-the-ground staff positions with little influence over study design. We find existing hierarchies and power structures in the academic research ecosystem compound challenges for equitable diversification. CONCLUSION: Our results suggest that meaningful diversification of PMR teams will only be possible when team equity is prioritized as a core value in academic research communities.

Social inequities and contemporary struggles for collective health in Latin America.

As part of a planned series from Global Public Health aimed at exploring both the epistemological and political differences in diverse public health approaches across different geographic and cultural regions, this special issue assembles papers that consider the legacy of the Latin American Social Medicine and Collective Health (LASM-CH) movements, as well as additional examples of contemporary social action for collective health from the region. In this introduction, we review the historical roots of LASM-CH and the movement's primary contributions to research, activism and policy-making over the latter-half of the twentieth century. We also introduce the special issue's contents. Spanning 19 papers, the articles in this special issue offer critical insight into efforts to create more equitable, participatory health regimes in the context of significant social and political change that many of the countries in the region have experienced in recent decades. We argue that as global health worldwide has been pushed to adopt increasingly conservative agendas, recognition of and attention to the legacies of Latin America's epistemological innovations and social movement action in the domain of public health are especially warranted.

Rethinking health research capacity strengthening.

Health research capacity strengthening (HRCS) is a strategy implemented worldwide to improve the ability of developing countries to tackle the persistent and disproportionate burdens of disease they face. Drawing on a review of existing HRCS literature and our experiences over the course of an HRCS project in Vietnam, we summarise major challenges to the HRCS enterprise at the interpersonal, institutional and macro levels. While over the course of several decades of HRCS initiatives many of these challenges have been well documented, we highlight several considerations that remain underarticulated. We advance critical considerations of the HRCS enterprise by discussing (1) how the organisation of US public health funding shapes the ecology of knowledge production in low- and middle-income country contexts, (2) the barriers US researchers face to effectively collaborate in capacity strengthening for research-to-policy translation, and (3) the potential for unintentional negative consequences if HRCS efforts are not sufficiently reflexive about the limitations of dominant paradigms in public health research and intervention.