Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network.

The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.

People with disability and privacy in precision medicine research: what's at stake?

Re-identification from data used in precision medicine research is presumed to create minimal risk but may disproportionately impact health disparity populations. We consider plausible privacy risks and the negative ramifications thereof for people with disabilities, the largest health disparity population in the USA, and suggest measures to address these concerns.

Studying the impact of translational genomic research: Lessons from eMERGE.

Two major goals of the Electronic Medical Record and Genomics (eMERGE) Network are to learn how best to return research results to patient/participants and the clinicians who care for them and also to assess the impact of placing these results in clinical care. Yet since its inception, the Network has confronted a host of challenges in achieving these goals, many of which had ethical, legal, or social implications (ELSIs) that required consideration. Here, we share impediments we encountered in recruiting participants, returning results, and assessing their impact, all of which affected our ability to achieve the goals of eMERGE, as well as the steps we took to attempt to address these obstacles. We divide the domains in which we experienced challenges into four broad categories: (1) study design, including recruitment of more diverse groups; (2) consent; (3) returning results to participants and their health care providers (HCPs); and (4) assessment of follow-up care of participants and measuring the impact of research on participants and their families. Since most phases of eMERGE have included children as well as adults, we also address the particular ELSI posed by including pediatric populations in this research. We make specific suggestions for improving translational genomic research to ensure that future projects can effectively return results and assess their impact on patient/participants and providers if the goals of genomic-informed medicine are to be achieved.

The need for an intersectionality framework in precision medicine research.

Precision medicine research has seen growing efforts to increase participation of communities that have been historically underrepresented in biomedical research. Marginalized racial and ethnic communities have received particular attention, toward the goal of improving the generalizability of scientific knowledge and promoting health equity. Against this backdrop, research has highlighted three key issues that could impede the promise of precision medicine research: issues surrounding (dis)trust and representation, challenges in translational efforts to improve health outcomes, and the need for responsive community engagement. Existing efforts to address these challenges have predominantly centered on single-dimensional demographic criteria such as race, ethnicity, or sex, while overlooking how these and additional variables, such as disability, gender identity, and socioeconomic factors, can confound and jointly impact research participation. We argue that increasing cohort diversity and the responsiveness of precision medicine research studies to community needs requires an approach that transcends conventional boundaries and embraces a more nuanced, multi-layered, and intersectional framework for data collection, analyses, and implementation. We draw attention to gaps in existing work, highlight how overlapping layers of marginalization might shape and substantiate one another and affect the precision-medicine research cycle, and put forth strategies to facilitate equitable advantages from precision-medicine research to diverse participants and internally heterogeneous communities.

Addressing underrepresentation in genomics research through community engagement.

The vision of the American Society of Human Genetics (ASHG) is that people everywhere will realize the benefits of human genetics and genomics. Implicit in that vision is the importance of ensuring that the benefits of human genetics and genomics research are realized in ways that minimize harms and maximize benefits, a goal that can only be achieved through focused efforts to address health inequities and increase the representation of underrepresented communities in genetics and genomics research. This guidance is intended to advance community engagement as an approach that can be used across the research lifecycle. Community engagement uniquely offers researchers in human genetics and genomics an opportunity to pursue that vision successfully, including by addressing underrepresentation in genomics research.

The effect of genetic education on the referral of patients to genetic evaluation: Findings from a national survey of nephrologists.

PURPOSE: The success of genomic medicine hinges on the implementation of genetic knowledge in clinical settings. In novel subspecialties, it requires that clinicians refer patients to genetic evaluation or testing, however referral is likely to be affected by genetic knowledge. METHODS: An online survey was administered to self-identified nephrologists working in the United States. Nephrologists' demographic characteristics, genetic education, confidence in clinical genetics, genetic knowledge, and referral rates of patients to genetic evaluation were collected. RESULTS: In total, 201 nephrologists completed the survey. All reported treating patients with genetic forms of kidney disease, and 37% had referred <5 patients to genetic evaluation. A third had limited basic genetic knowledge. Most nephrologists (85%) reported concerns regarding future health insurance eligibility as a barrier to referral to genetic testing. Most adult nephrologists reported insufficient genetic education during residency (65%) and fellowship training (52%). Lower rating of genetic education and lower knowledge in recognizing signs of genetic kidney diseases were significantly associated with lower number of patients referred to the genetic evaluation (P < .001). Most nephrologists reported that improving their genetic knowledge is important for them (>55%). CONCLUSIONS: There is a need to enhance nephrologists' genetic education to increase genetic testing use in nephrology.

Education and electronic medical records and genomics network, challenges, and lessons learned from a large-scale clinical trial using polygenic risk scores.

Polygenic risk scores (PRS) have potential to improve health care by identifying individuals that have elevated risk for common complex conditions. Use of PRS in clinical practice, however, requires careful assessment of the needs and capabilities of patients, providers, and health care systems. The electronic Medical Records and Genomics (eMERGE) network is conducting a collaborative study which will return PRS to 25,000 pediatric and adult participants. All participants will receive a risk report, potentially classifying them as high risk (∼2-10% per condition) for 1 or more of 10 conditions based on PRS. The study population is enriched by participants from racial and ethnic minority populations, underserved populations, and populations who experience poorer medical outcomes. All 10 eMERGE clinical sites conducted focus groups, interviews, and/or surveys to understand educational needs among key stakeholders-participants, providers, and/or study staff. Together, these studies highlighted the need for tools that address the perceived benefit/value of PRS, types of education/support needed, accessibility, and PRS-related knowledge and understanding. Based on findings from these preliminary studies, the network harmonized training initiatives and formal/informal educational resources. This paper summarizes eMERGE's collective approach to assessing educational needs and developing educational approaches for primary stakeholders. It discusses challenges encountered and solutions provided.

Precision medicine and the problem of structural injustice.

Many countries currently invest in technologies and data infrastructures to foster precision medicine (PM), which is hoped to better tailor disease treatment and prevention to individual patients. But who can expect to benefit from PM? The answer depends not only on scientific developments but also on the willingness to address the problem of structural injustice. One important step is to confront the problem of underrepresentation of certain populations in PM cohorts via improved research inclusivity. Yet, we argue that the perspective needs to be broadened because the (in)equitable effects of PM are also strongly contingent on wider structural factors and prioritization of healthcare strategies and resources. When (and before) implementing PM, it is crucial to attend to how the organisation of healthcare systems influences who will benefit, as well as whether PM may present challenges for a solidaristic sharing of costs and risks. We discuss these issues through a comparative lens of healthcare models and PM-initiatives in the United States, Austria, and Denmark. The analysis draws attention to how PM hinges on-and simultaneously affects-access to healthcare services, public trust in data handling, and prioritization of healthcare resources. Finally, we provide suggestions for how to mitigate foreseeable negative effects.

How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia?

Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry.

Increasing inclusivity in precision medicine research: Views of deaf and hard of hearing individuals.

PURPOSE: Deaf/hard of hearing (HoH) individuals can benefit from precision medicine research (PMR) but are underrepresented in mainstream health research and may experience barriers to participation. Understanding their views and concerns about PMR can inform processes to foster inclusion in future studies and reduce health disparities. METHODS: We administered an online disability-accessible survey to explore perceptions of PMR among, inter alia, deaf/HoH individuals. Questions included willingness to participate, interest in results, and barriers and facilitators to participation. Analyses describe results for participants who self-identified their primary condition as being deaf/HoH and compared results for key demographic characteristics. RESULTS: A total of 267 deaf/HoH participants completed the survey. Interest in PMR was high, although many reported inaccessible facilities and information about medical research; 51% reported that communication with health professionals is a barrier. Concerns about harm, lack of access to benefits, misinformed allocation decisions, and limited disability-relevant knowledge among researchers and health care providers were significant. Differences across racial, ethnic, and sex groups were observed and are discussed. CONCLUSION: Strategies to remove barriers to participation of deaf/HoH individuals in PMR are suggested. Distrust is a major challenge for cohort diversity, and research is needed to identify measures to increase the trustworthiness of PMR endeavors.

Structural Racism in the COVID-19 Pandemic: Moving Forward.

The COVID-19 pandemic has taken a substantial human, social and economic toll globally, but its impact on Black/African Americans, Latinx, and American Indian/Alaska Native communities in the U.S. is unconscionable. As the U.S. continues to combat the current COVID-19 cycle and prepares for future pandemics, it will be critical to learn from and rectify past and contemporary wrongs. Drawing on experiences in genomic research and intersecting areas in medical ethics, health disparities, and human rights, this article considers three key COVID-19-related issues: research to identify remedies; testing, contact tracing and surveillance; and lingering health needs and disability. It provides a pathway for the future: community engagement to develop culturally-sensitive responses to the myriad genomic/bioethical dilemmas that arise, and the establishment of a Truth and Reconciliation Commission to transition the country from its contemporary state of segregation in healthcare and health outcomes into an equitable and prosperous society for all.

Disability, Ethics, and Health Care in the COVID-19 Pandemic.

This article considers key ethical, legal, and medical dilemmas arising for people with disabilities in the COVID-19 pandemic. We highlight the limited application of existing frameworks of emergency planning with and for people with disabilities in the COVID-19 pandemic, explore key concerns and issues affecting the health care of people with disabilities (i.e., access to information and clinician-patient communication, nondiscrimination and reasonable accommodations, and rationing of medical goods), and indicate possible solutions. Finally, we suggest clinical and public health policy measures to ensure that people with disabilities are included in the planning of future pandemic-related efforts.The devastation evoked by the COVID-19 pandemic raises challenging dilemmas in bioethics. It also speaks to social justice issues that have plagued historically marginalized communities in the United States.Responses to the pandemic must be bound by legal standards, principles of distributive justice, and societal norms of protecting vulnerable populations-core commitments of public health-to ensure that inequities are not exacerbated, and should provide a pathway for improvements to ensure equitable access and treatment in the future.

Disability inclusion in precision medicine research: a first national survey.

PURPOSE: Including people with disabilities in precision medicine research (PMR) is key for increasing cohorts' diversity, improving understanding of population health, and attaining social justice for the United States' largest health disparities group. We conducted a national survey to explore the views of people with disabilities about PMR. METHODS: An online survey was developed in disability-accessible formats. Key questions included views on PMR, willingness to participate and to provide data, perceived barriers to participation and potential remedies, and interest in engagement in the study. Analyses described results for all participants and compared results for key demographic characteristics. RESULTS: In total, 1294 participants completed the survey. Participants expressed strong support for PMR, and willingness to participate in PMR; to provide lifestyle, biological, and medical information; and to engage with the study. However, 76% identified a total of 3 to 8 barriers to participation, and most would not provide environmental samples or information from their social media account(s) and activity trackers. Differences were observed across racial, ethnic, and gender groups and are discussed. CONCLUSIONS: Barriers to disability inclusion need to be removed, and further research conducted to better understand concerns about PMR and to develop studies that resonate with the interests and needs of this population.

Increasing genomic literacy among adolescents.

PURPOSE: Adolescents increasingly need to be "genomics literate," and may engage more with video educational formats than traditional written formats. We conducted a pilot study to assess and compare the impact of two modes of education about genome sequencing (GS) on adolescents' genomic knowledge and genomic-related decisions. METHODS: Using an online survey, 43 adolescents ages 14-17 years were randomly assigned to watch a video or read a pamphlet about GS. Measures included pre- and postintervention assessment of genomic knowledge, perceived utility of these materials for decisions about participating in genetic research, interest in receiving GS results, and overall satisfaction with these materials. Analyses described results for all participants and compared results between intervention groups. RESULTS: Self-reported genomic knowledge increased overall (p < 0.001). Postintervention knowledge about GS limitations was higher among video group than pamphlet group participants (p = 0.038). More video group than pamphlet group participants expressed satisfaction with the material's understandability (45% vs. 29%) and suitability (91% vs. 76%). Interest in receiving personal GS results was significantly associated with being female (p = 0.01) and younger (14-15 years vs. 16-17 years) (p = 0.002). CONCLUSION: A video format may be preferable for increasing genomic literacy among adolescents. Further research with adolescents is needed to better understand how gender and age may impact genomic decisions and preferences.

Including the blind community in precision medicine research: findings from a national survey and recommendations.

PURPOSE: Despite ongoing efforts to increase diversity of cohorts in precision medicine research (PMR), little is known about the obstacles to inclusion of blind people and those with low vision ("the blind community") in PMR. The blind community comprises ~10% of the US adult population and its members commonly experience health disparities. Understanding barriers to inclusion of this community is necessary to facilitate their participation. METHODS: An online survey was developed in disability-accessible formats. Key questions included views on PMR; willingness to participate, provide data, and engage in the study; data sharing and consent; and perceived barriers to participation. Analyses describe results for all participants. RESULTS: Two hundred seventy-one blind/low-vision participants completed the survey. Participants expressed strong support for PMR, and willingness to participate in PMR, to provide lifestyle, biological and medical information, to engage with the study, and to have their data shared with other researchers. Preferences for data sharing and consent models varied. Significantly, 65% identified 3-6 barriers to participation, particularly inaccessible transportation, clinics, and facilities; inaccessible information; and attitudinal and institutional barriers. CONCLUSION: Removing the identified barriers is key. Measures that could increase inclusivity of blind people and those with low vision in PMR are suggested.