The need for an intersectionality framework in precision medicine research

Summary

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.

Graphical abstract

Cohort diversity in precision-medicine research is critical for promoting equitable health outcomes. Sabatello et al. explore key issues—(dis)trust, translational efforts, and responsive community engagement—to highlight the need for an intersectional framework that considers how multiple and overlapping factors (e.g., race, disability, and gender) jointly interact to impact research participation.

Introduction

Precision-medicine research raises hopes for preventive, diagnostic, and treatment options that take account of each person’s biological, genetic, environmental, and lifestyle factors. However, although the ability of precision-medicine research to develop generalizable knowledge and to offer benefits that can accrue to everyone hinges on the existence of large and diverse cohorts, studies consistently show disparities in enrollments into genomic and precision-medicine research. To date, diversification of cohorts has largely focused on increasing participation by women and racial and ethnic minoritized communities. The All of Us Research Program (AoURP), the national precision-medicine research initiative run by the National Institutes of Health, has emphasized enrollment of historically marginalized racial and ethnic communities and other underrepresented groups in biomedical research.¹ However, analyses of nuanced representation in the AoURP is lacking, and the data needed to allow assessment of diverse participation in other existing cohorts is often unavailable.

Although race and ethnicity are often considered the primary axes of identity in discussions on participation in precision-medicine research, racial and ethnic communities are neither homogeneous nor monolithic. Beyond a binary identification based on race and ethnicity (e.g., whether a participant is Hispanic or Indigenous), factors such as (dis)ability, sexual orientation, gender, class, residence (e.g., rural/urban, institutions/community dwelling), culture, and country of origin affect the lived experiences of individuals within these communities and are likely to affect participation in precision-medicine research. Moreover, contrary to the use of group-level analysis in precision-medicine research studies, translating knowledge from precision-medicine research to improved health outcomes at the individual and population levels (“translational efforts”) requires focusing on the full spectrum of an individual’s attributes. Yet only limited work exists about these aspects of diversity and, especially, how marginalization within minoritized racial and ethnic groups might impact participation in, and access to the benefits of, precision medicine research.

In this commentary, we consider three key issues where overlapping layers of marginalization might impede the promise of precision-medicine research: (dis)trust and representation, translational efforts to improve health outcomes, and responsive community engagement. We argue that common approaches to considering marginalization fall short and that a more nuanced—multi-layered and intersectional—approach to data collection, analyses, and implementation is needed if we are to achieve cohort diversity and community-responsive precision medicine research. An intersectional approach is useful because it considers how multiple categories of sociopolitical identity shape and substantiate one another and how systems of power and privilege create and maintain lived experiences of marginalization.² It highlights the fact that experiences of advantage and disadvantage are not “additive” in their effect and challenges the common assumption that it is possible to separate these experiences and add them into one sum. Rather, intersecting experiences synergistically shape and create distinct experiences that need to be considered jointly.³ We draw attention to gaps in existing work and offer strategies to facilitate the assurance that diverse participants and communities derive equitable benefits from precision-medicine research.

(Dis)trust and representation

Distrust is commonly postulated as a key barrier to the participation of minoritized racial and ethnic communities in biomedical research, including precision-medicine research. This distrust is the result of notorious incidents of research-related abuse and exploitation, such as the U.S. Public Health Syphilis Study at Tuskegee on Black and African American individuals and the genetic studies on members of the Havasupai Tribe, and the intergenerational trauma that has ensued.^4,5 Studies with marginalized racial and ethnic communities have further found that distrust in precision-medicine research in a community that experienced mistreatment in research (e.g., African Americans) transcends to other minoritized communities (e.g., the Hispanic/Latino and Asian communities) and erodes their trust in precision-medicine research as well.⁶ More generally, experiences of racism, whether by an individual or by a group an individual identifies with, in clinical and research settings are associated with perceptions of lack of trustworthiness of precision-medicine research.⁶

Less is known about the representation of, and distrust among, marginalized communities within racial and ethnic groups in precision-medicine research. Sexual and gender minorities and people with disability might experience additional forms of systemic discrimination that can sow distrust and impact recruitment efforts. Studies of transgender people, for example, have found distrust of clinicians and high prevalence of negative clinical encounters, including in genomic medicine and research⁷; these experiences were compounded among transgender people who identify as belonging to other marginalized groups (e.g., people of color, people with disability)⁸ and may exacerbate concerns about participation in precision-medicine research. Similarly, a study of people with disability found that, while accessibility, economic, communication and attitudinal barriers to participation were significant for all participants, as a group, participants experiencing higher levels of financial insecurity reported far more barriers than others.⁹ It also found that interest in participation was lower among participants with disability from minoritized racial and ethnic groups, and those from (dis)ability communities for whom medical genetics has been viewed as paternalistic and even genocidal (e.g., deaf or hard-of-hearing individuals).^9,10

How such diverse and overlapping experiences of marginalization interact and affect participation in precision-medicine research is understudied; analyses of existing cohorts are stymied by small sample sizes and data-collection practices that, without focused attention, are unlikely to be remedied by the growing expectations for data sharing. Participants’ demographic information is often limited to categories that are required for reporting purposes, such as binary sex, which is insufficiently specific and does not reflect the range of lived experiences of either sex or gender.¹¹ Other constructed categories, such as (dis)ability status, are rarely collected in mainstream (i.e., not disability-specific) precision-medicine research studies. Moreover, although collecting data on participants’ obstacles to participation and experiences of discrimination could provide valuable insights into the sources of distrust that affect interest in precision-medicine research, these data are often not systematically collected or reported. This lack of nuanced data-collection practices impedes our understanding of the barriers faced by those at the intersections of multiple marginalizations and our ability to develop, implement, and evaluate strategies to remove these barriers.

Translational efforts: Beyond individual results

A major hope for precision-medicine research is that individuals and communities will become better aware of their genetic risks for developing health conditions and take action to reduce these risks. The growing practice—and expectation—of returning individual genetic results to participants in precision-medicine research emerged from this goal.¹² Yet, current practice in genomic research only minimally considers how participants access and respond to their genetic results. It also rarely assesses long-term implementation of treatments or behavioral changes in response to the results or whether and how marginalized communities (different than individuals) stand to benefit from precision-medicine research, including return of results, to improve community health.¹³ These gaps can further disenfranchise marginalized communities.

For example, studies have found lower interest in receiving research-based genetic results among African Americans than among White participants because of a lower expectation of health benefits.¹⁴ Women have also been shown to be more likely than men to learn about and act on their genetic predispositions.¹⁵ Similarly, a study of people with disability found lower interest in genetic results among Black and African American participants, although unlike studies of the general public, also among women compared to men.¹⁶ These findings might stem from concerns about increased racial and disability stigma, restrictions on reproductive freedom¹⁷—reminiscent of eugenics—and being blamed for inaction in response to the results. Meanwhile, systemic issues such as no access to follow-up care, misperceptions among clinicians and researchers about the worthiness of diverse bodies, and inaccessible platforms for returning results or providing information about risk-reducing measures are ignored. Whether these (or other) reasons are prominent across, and within, the various sociopolitical categories of identity (e.g., race, ethnicity, sexual orientation, gender, (dis)ability, class) is understudied. Yet, each of these reasons—both independently and especially in interaction with others—can produce lower interest in receiving genetic results.

An intersectional approach that considers the social determinants of health could promote a more refined understanding and address the complexities by informing researchers about the overlapping barriers and help identify remedies that correspond with the interpersonal-, institutional-, and structural-level challenges that preclude equitable implementation of translational efforts. The “social determinants of health” framework, as developed by the World Health Organization¹⁸ and the U.S. Healthy People 2030 framework,¹⁹ identified five key domains that affect human flourishing: economic stability, education access and quality, healthcare access and quality, neighborhood and built environment (as assessed, e.g., by zip codes), and social and community context. These domains affect individuals uniquely and should guide the approach to the translational efforts of precision-medicine research.^20,21 For example, a study of Hispanic individuals found that interest in the return of genomic results from research was associated with levels of income and especially, education.²² Those with lower education perceived a lower value of pharmacogenomic results than did those with higher education, highlighting the need for culturally and linguistically targeted information as well as the importance of increasing educational attainment on a systems level.²² Although some efforts to more easily integrate social determinants of health into precision medicine within healthcare settings are underway,²³ they will have limited impact unless precision-medicine research studies systematically collect and integrate social determinants of health data into intersectional analyses to inform the subsequent development of policy recommendations.²⁴

Concurrently, a framework of social determinants of health calls for moving away from precision-medicine research’s exclusive focus on individuals who receive results to population health. Continuing the education example above: Healthy People 2030 redefines health literacy to encompass both personal and organizational capabilities that affect individuals’ ability to find, understand, and make informed health decisions and actions.²⁵ In precision-medicine research, this conceptualization would consider an individual’s education as a relevant factor but also uphold the responsibility of researchers and research institutions to increase health and genomic literacy of research participants at both individual and population levels. This could include providing genetic counseling services free of charge to ensure that research participants understand the meaning of results and their health implications, distributing health-related material and the results themselves in accessible formats (e.g., compatible with text-to-read programs that are used by blind individuals), utilizing patient navigators to assist participants with the interpretation of the results, connecting research participants with support groups for people with similar conditions, encouraging research participants to share their emerging health and genomic knowledge with others (e.g., family relatives, community members), instituting system-level policies to ensure health coverage for genetic counseling,²⁶ and assuring stronger legal protections to reduce the risks of genetic discrimination in coverage of life insurance, disability insurance, and long-term care (which are not currently protected under the Genetic Information non-Discrimination Act).

Other approaches that incorporate social determinants of health categories could operationalize social positions in ways that are tailored to advance health outcomes of (sub)populations. For example, given that health education is intertwined with economic stability,²⁷ studies could develop processes to ensure access to follow-up care to participants from diverse socioeconomic backgrounds after results are returned (e.g., by covering related costs). They could also identify more granular units of analysis in each domain of social determinants of health (e.g., by using years of education rather than dichotomized categories in data analyses or evaluating levels of financial instability and its association with environmental degradation) while incorporating new measures to assess the quality of education and health services that are provided in poorer geographic locales.²⁸ The intersectionality approach might not provide immediate solutions for all questions surrounding precision-medicine research. However, its significance lies in the call for new evaluation of existing research methods, emphasis on the need to develop innovative approaches to explore the complex interactions that impact health outcomes, and demand for active efforts to address the root causes of health disparities of populations that are at the intersection of multiple social positions and identity.

Community engagement

Engaging marginalized communities in precision-medicine research has gained momentum as a “best practice” to improve compatibility between research endeavors and community needs, build rapport between researchers and participants, and increase organizational commitment to accountability while enhancing diverse recruitment.^29,30 Community engagement encompasses a bidirectional learning process and justice-oriented goals, including enhancing researchers’ awareness, cultural humility, self-reflection on biases, and understanding of diverse health constructs and sociopolitical power imbalances.²⁹

However, existing practices for community engagement are unlikely to capture, and respond to, diversity within communities. Beyond the gold standard of community-based participatory research, community engagement encompasses many forms, some of which (e.g., outreach) involve limited substantive interaction with communities.²⁹ Information about the engaged community members is commonly unavailable beyond a single-axis attribute (e.g., race), if it is available all, reinforcing misperceptions of homogeneous communities and precluding the generation of knowledge about the representation of community members with overlapping marginalization—each of which can have ramifications for study goals, design, and implementation. Community engagement is further sometimes conflated with “stakeholder engagement,” although the latter includes a range of actors, some of whom might hold worldviews discordant to those of individuals with lived experience of marginalization (e.g., whether being deaf or autistic is a disability). Although the paramountcy of lived experience in research ethics might seem exaggerated to some,³¹ it must be considered from the perspective of unequal systems and power dynamics.³² In research settings, the risk is that minoritized community members and researchers, especially those with overlapping experiences of marginalization, are outnumbered and overpowered by more privileged participants in decision-making forums such as institutional review boards.^33,34

Although community engagement inherently involves only partial representation, diversity beyond a single-axis attribute (e.g., race, gender, age) is critical for precision-medicine research to deliver on its promise to be responsive to the health needs of all marginalized communities. Developing clear purpose and measures for community engagement in precision-medicine research, requiring that community-engaged studies include diversity reporting, and implementing approaches to evaluate the community-engagement process and outcomes can improve understanding of whose voices are missed in conversations about precision-medicine research and can guide researchers and funders to invest in more inclusive community-engagement efforts. Effective community engagement further necessitates taking steps to ensure that community members, including those at the intersection of marginalized identities, are empowered to partake in the dialogue on precision-medicine research.

The empowerment component in community-engaged precision-medicine research can be informed by the “Culturally Responsive Teaching” framework. Culturally Responsive Teaching—and its variations, e.g., culturally responsible, culturally congruent, culturally compatible, culturally appropriate, and culturally sustaining teaching³⁵—has been developed and used in the field of education for more than two decades.^36,37 It argues that student academic achievement is enhanced when educational practices and teacher–student interactions are within the nexus of the child’s culture and community environment, and it calls on teachers to support students’ leadership in incorporating cultural values and contexts into educational projects.³⁶

Expanding Culturally Responsive Teaching to community-engagement efforts in precision-medicine research is helpful in two key areas. First, it highlights the focus on the experiences and understanding of the end-users. Thus, for example, community engagement can be employed to develop study materials³⁸ that are responsive not only to those who identify on a single-axis datapoint (e.g., Hispanic, Black/African American) but also to those who are marginalized within marginalized communities (e.g., Black Deaf transgender individuals, for whom Black American Sign Language³⁹ and transgender-inclusive practices are important^40,41). Second, like teachers using Culturally Responsive Teaching, researchers should demonstrate openness to multicultural and intersectional perspectives—for instance, the meaning and experiences of being an Indigenous person with disability, for whom scientific colonialism³⁸ and scientific ableism, as well as unique Indigenous concepts of disability, are likely to exist.⁴² Although diversity training can be expanded to encompass marginalized communities beyond the race/ethnicity axis and intersectionality, it is challenging to effectively implement⁴³ and is not a panacea for prejudices that result in exclusion or mistrust.⁴⁴ Culturally responsive community engagement throughout and after the study cycle offers an opportunity for ongoing interactions between researchers and their community member partners and can improve understanding of heterogeneous contexts and values within these communities. Such personal relationships—built on mutual trust and respect—have been shown to reduce biases⁴⁵ and increase cultural humility.⁴⁶

Conclusions

Precision-medicine research holds great potential to improve personalized care and reduce health disparities. However, the realization of this potential depends on recognition of the multiple, overlapping, and intricate layers of marginalization that individuals can experience and identification of measures to address the synergetic barriers that these experiences have on research participation and equitable access to precision-medicine research benefits. To advance policies and practices that address gaps in existing studies, precision-medicine research should adopt an intersectional approach for data collection, analysis, and implementation. This framework considers more than binary or single-axis demographic characteristics and can better inform challenges related to (dis)trust and representation, translational efforts, and culturally responsive community engagement. By creating inclusive, contextually aware, and harmonized data-collection practices, knowledge dissemination, and engagement strategies, precision-medicine research can pave the way for identifying the communities within communities that are left behind and ensuring that they too can partake in, and benefit from, the promise of precision-medicine research.