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

Abstract

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.

Introduction

As support for precision medicine – a field that aims to improve prevention, diagnosis, and treatment by accounting for individual variability in genes, environment, and lifestyle – has accelerated in the USA, both funders and investigators have acknowledged a serious challenge [1]. To ensure that advances in this field benefit all Americans, precision medicine research (PMR) and the data on which it is based must become far more inclusive of minoritized groups in the USA, as well as diverse populations globally. With regard to the genomic data at the core of the precision research enterprise, numerous experts have warned that without decisive action to better capture genetic ancestral diversity in PMR databases, population-specific mutations associated with non-European populations will likely be missed and health disparities worsened [2–5]. Others have cautioned that PMR must include minoritized communities in translation studies in order to ensure equity in future access to and implementation of its innovations [4, 6, 7].

In response to these challenges, the US National Institutes of Health (NIH) and Federal Drug Administration (FDA) have prioritized the enrollment of diverse participants for PMR in guidance and funding solicitations [3, 8], urging that researchers reverse historically low rates of inclusion in clinical trials persistent across most biomedical research fields [9–13]. With measured success [14], precision medicine researchers are increasingly expanding their outreach, recruitment, and retention of historically underrepresented communities, especially minoritized communities of color. This has also necessarily involved increased interaction with low-resource and medically underserved communities due to historic and ongoing systemic racism that broadly disadvantages communities of color [15]. Some researchers are, for example, expanding the infrastructure necessary to partner with and conduct PMR at low-resource clinical sites, such as federally qualified health centers [16].

Barriers driving low rates of research participation among minoritized communities have been widely examined [17, 18]. A recent systematic review of factors influencing racial and ethnic minorities’ participation specifically in genetic research found that while mistrust of healthcare providers and systems is often generalized as the primary barrier to participation, mistrust (or lack of perceived trustworthiness) does not fully explain lower participation [19]. Other important factors included access to and awareness of research opportunities, competing priorities in the daily lives of potential participants, concerns over privacy and discrimination, and – of particular interest here – the potential direct benefits of participating in a given study [19]. Despite these findings, policy discussions across the field and empirical analyses investigating benefit have remained narrowly focused on the return of individual research results to participants [20].

In this paper, we examine the experiences of US-based investigators and frontline research staff, who are working to engage minoritized communities in PMR, in order to assess how standard approaches to benefit are received, contested, and negotiated “on the ground.” In numerous cases, the researchers we interviewed challenged standard approaches to benefit and responsibility in PMR. Their reflections indicate a common experience of “moral distress” at the frontlines of PMR targeting diverse communities, defined as “ethical unease or disquiet resulting from a situation where a clinician believes they are contributing to avoidable patient or community harm through their involvement in an action, inaction, or decision that conflicts with their own values” [21, p. 207]. Our interviewees’ reflections also point to alternative benefits that researchers and bioethicists may consider in planning future studies and revising research guidelines and policy.

Reconsidering Benefit and Responsibility

Historically, researchers and bioethicists have framed research participation as an act of altruism, free from expectations of direct benefit. Instead, the calculus of beneficence (i.e., risk-benefit assessment) underpinning ethics protocols typically emphasizes the broad, aspirational benefit of advancing scientific knowledge [22]. As King [23] noted, the Common Rule includes limited language addressing benefit, calling only for consideration of “the potential benefits of the research to the subjects and others and the importance of the knowledge gained or to be gained” [24]. While these guidelines are intended to inform research governance and approval practices of Institutional Review Boards (IRBs), there remains a notable absence of language focusing on any meso-level benefit between that provided to individual participants and the broader societal-level benefits of advanced knowledge.

Further, in contrast to a clinician’s fiduciary responsibility for the care and wellbeing of their patient, it is widely accepted that a researcher’s top priority is to seek generalized knowledge for societal benefit. Indeed, researchers are constrained by their obligation to follow a research protocol, even when this necessarily excludes some participants’ broader needs [25]. This presumed distinction between research and clinical care has been foundational to both 20th-century bioethics and health law, and governing policies and guidelines continue to endorse this perspective [26].

Contrary to these conventions, the expectation and actual accrual of a range of benefits to research participants are routine in practice, though largely unrecognized. Benefit is especially clear in oncology, where the integration of research and care has become near-standard and research participation frequently offers access to emerging therapies [27]. AIDS treatment activists also powerfully positioned access to emerging HIV therapies via research participation as a social good that should be equitably distributed [28]. More recently, in the context of cardiovascular drug trials, Wadmann and Hoeyer [29] documented benefits that researchers provide (typically informally) to participants, including referrals to social services, sharing of insider information about the healthcare system, and friendship and emotional support.

Within genomic and precision medicine, one proposed alternative to the sharp research/care divide is a reciprocity-based framework, in which researchers explicitly bear some responsibility (if narrow) for the individualized care of participants who entrust them with their data and specimens. Proponents of this framework have built broad consensus around researchers’ duties to return actionable individual-level research results. While some opponents have “objected to refocusing research effort away from creating generalized knowledge to conferring individual benefit” and to “devoting scarce research dollars to identifying individual problems for clinical pursuit” [30, p. 448], the accepted calculus of researcher responsibility and benefit to participants has already begun to shift in these fields.

Global health experts and practitioners, especially those working within and across African nations, increasingly debate a broader set of benefits potentially owed to research participants in return for their participation. For example, the ethical framework of ancillary care [31–33], thus far adopted primarily in the context of HIV/AIDS research in low-resource settings [34, 35], delineates the obligations of researchers to provide additional medical care and non-medical support to research participants. The framework suggests a responsibility to provide services beyond those necessary “to answer the scientific question (or) to avoid or mitigate harm resulting from participation in the research” [36, p. 709].

Global health ethicists have also argued that researchers have a responsibility to communities in developing-country contexts where internationally funded research is carried out [37–39]. Such benefits include expectations around the “reasonable availability” of innovations following the research stage or, more generally, investments in local human and health infrastructure capacity building [40–42]. More recently, researchers have documented growing expectations around “benefit sharing” as a necessary component of ethical global health research [43–46]. Benefit sharing, in the long term, aims to equitably distribute profit generated by research innovation, for example, by funding healthcare or educational infrastructure to foster the wellbeing of entire communities from which research participants are drawn.

As we show below, the experiences and reflections of many researchers in US-based PMR echo and build upon these global debates over what broader benefits are owed, to whom, and within what timeframe. The emerging debate we describe, however, re-situates these concerns within the sphere of US-based domestic research, where the state’s interest in advancing science overlaps with its responsibility to ensure the basic welfare of its citizens. Further, in the case of international research, scientists not only negotiate the terms of ethical practice with their own IRB, but they also observe protections established by sovereign foreign governments. Typically, no such formal gatekeeper exists to collectively negotiate the terms of research on behalf of the racially minoritized and socioeconomically disadvantaged communities now increasingly targeted for PMR in the USA. Finally, funders and scientists involved in PMR have widely framed their push to engage diverse participants not simply as a practicality of research but rather as an issue of social justice and racial inclusion. Such invocations of justice have raised the stakes regarding the tangible difference PMR participation will make for participants and their communities.

Methods

Study Design

The data reported here are drawn from a multi-sited, qualitative project examining how commitments to diversity and inclusion are interpreted and operationalized in five ongoing studies across three national PMR consortia. Five PMR studies were selected to maximize geographic diversity of the study sites, capture heterogeneous strategies to engage, recruit, and retain underrepresented individuals as research participants, and, as studies were at different stages of their rollout, provide maximum insight into study practices across the research “lifecourse” (i.e., from the development of funding mechanisms to study design, enrollment, data collection and analysis, and dissemination and translation of findings).

We committed to maintaining the confidentiality of the five study names and other clearly identifying details. We also maintained the anonymity of the individuals we interviewed. The three national consortia from which these five studies are drawn include: a large-scale initiative recruiting diverse participants through regional study sites to build a database for future research; another consortium funding ongoing cohort studies to integrate genomic analyses; and a third consortium funding studies to examine the translation of precision findings in clinical care. Institutional Review Board approval for this project was obtained from (blinded for review).

Data Collection

Our project included 125 in-depth interviews (60–90 min each) conducted between July 2019 and December 2021 with a purposive sample of investigators, research staff, community advisory board members, and NIH program officers linked to these 5 PMR studies. Interviews explored experiences with engagement, recruitment, and retention of underrepresented participants, as well as data analysis and dissemination of findings. Interview guides were tailored according to investigator and staff roles to ensure that questions were appropriate for each participant. Additionally, we conducted observations of study team and consortium meetings and scientific conferences totaling approximately 450 h, during which we took detailed fieldnotes. These observations informed our ongoing interviews. We obtained verbal informed consent for all observations and written informed consent for all interviews. We also reviewed 76 key documents (e.g., funding solicitations, research publications, consent forms, and recruitment materials) linked to these studies and consortia.

The theme of “moral distress” discussed in this paper was not initially included in our interview guides, but rather emerged inductively during ongoing analysis. We incorporated specific questions about benefit into interview guides, only after multiple interviewees brought up these issues (including respondents working at the front lines of research and more senior members of research teams).

While maintaining the anonymity of our interviewees, we also include indicators of their social positions. For this, we draw on their responses to open-ended demographic questions posed at the conclusion of our interviews – across race, ethnicity, and gender – that were necessary to meet our study’s NIH reporting requirements. We include this information to situate our informants as both gendered and racialized individuals, each with distinct proximities to the minoritized communities they interacting with. Additional dimensions of social difference that we did not capture may also be relevant.

Data Analysis

All interviews were recorded and professionally transcribed verbatim. Following a modified grounded theory approach [47], the research team generated an initial codebook based on study aims, the existing literature, and issues that had arisen repeatedly throughout data collection. Using the qualitative analysis software, Dedoose, the research team coded a small sample of documents, interview transcripts, and observation fieldnotes to test this initial codebook’s effectiveness and to generate inductively additional codes. Through consecutive waves of independent and joint coding, followed by discussion and reconciliation, we finalized a codebook of 176 codes. For this analysis, from this larger set, we extracted data using codes related to the promise of PMR, research impact, participant motivations, managing participant expectations, responsibility, and trust. The quotes included below are illustrative of the subset of data collected related to these codes.

Results

Below, we show that while some interviewees considered a standard approach to conceptualizing benefit – that is, an emphasis on the eventual advancement of scientific knowledge – to be sufficient, others contested this as an acceptable framework through which to articulate what is owed by researchers to the individuals and communities they engage in PMR. Further, when confronted with unmet clinical, psychosocial, and material needs within the communities where they were working, some of our interviewees reported ethical uncertainty regarding the limits of their responsibility to provide assistance or help participants obtain care. In response, some interviewees improvised within their research roles to meet what they perceived as their ethical obligation to provide forms of care and other resources to those in need. Others expressed moral distress at not being able to do so.

Scientific Advancement: A Promise Unfulfilled

In discussing the recruitment of diverse research participants, specifically from communities previously underrepresented in genomic databases, one senior investigator, a white man, contended that research participation is the only way that communities can ensure they will benefit from precision medicine advances:

The argument in large measure to these populations is, if you want your community to benefit. You can’t stand by and say, “well, let people from other backgrounds participate; we don’t trust [researchers].” It’s important right now for us to communicate to these communities that if this is an investment in the future, then participate now, and there’ll be long-term benefits, potentially. You can’t really know for certain [there] will [be]. But you can know for certain there won’t be if they don’t participate.

While this investigator accepted as a given that the communities his study was targeting may “potentially” – but not definitely – experience medical benefits and improved health, numerous others we interviewed troubled the idea that the prospect of a “potential” health benefit was sufficient. Indeed, many challenged the value of scientific progress to the communities being recruited. Especially as they recruited from low-resource and medically underserved communities, our informants were concerned with a model of biomedical research that seems to produce myriad publications, but not necessarily better health outcomes.

As one investigator, a Black woman, put it, “collecting data for data’s sake, it’s just not okay. It’s not just about knowledge production. It’s also about action.” She added, “I mean, do you really want to make a difference, or do you want to continue to just study these things and not actually show any improvement in the health of people and communities?” This question of “science for what?” and “science for whom?” were common themes for participants in our study.

Several researchers reported that the lack of evident benefit sometimes led to tension in their ongoing interactions with community members. The same researcher, who questioned “data for data’s sake,” noted her study had been ongoing in an underserved community for more than a decade and continued:

I think it’s an ethical issue that we pump billions of dollars into this work and many of the participants don’t see any benefit to themselves or their communities even after many, many years of studying them. And communities have often said, “Oh, you come and get your data, but nothing ever happens. We give you our time. We literally give you our blood, our sweat. And nothing ever happens.”

She went on to endorse the importance of collaboration between investigators and policymakers to implement already existing public health knowledge, especially for the timely benefit of communities where research has been conducted. At the same time, she acknowledged that her own promotion and tenure depended on publications and that no formal mechanism existed by which meaningful policy engagement would also further the long-term security of her job.

Additionally, some researchers cautioned that the kind of health information that PMR studies promise to make available most quickly would have only a limited impact. For example, the impact of returning individually tailored risk scores accompanied by recommendations for behavioral modification would still be constrained by broader structural determinants negatively influencing health in these communities. For example, one senior investigator, a white man, expressed this frustration:

Underlying a lot of this, though, is socioeconomic challenges, right? I mean, it is more expensive to eat healthy than it is to eat poorly in this country. I don’t have any power to change that. Changing that’s going to take an act of Congress.

It was also clear that our informants understood that the stakes were especially high with regard to the fragile relationships they were building with communities previously underrepresented in biomedical research. Citing the ways in which the scientific enterprise has historically exacerbated marginalization, several noted a sense of responsibility to ensure that promises made were kept. As one senior investigator, a white woman, explained:

I don’t think science has a particularly good reputation for taking the people upon which the project design is built into consideration. And I think that many communities have very reasonable mistrust, actual mistrust of science at the end of research [studies] exactly like this. And I think we’re asking an awful lot of people; we’re asking for very sensitive information, we’re asking for a lot of it, and we’re asking them to trust us with that. And I think if it’s misused, it can both do damage to individuals, it can also do damage to communities, to groups of people, and it can do damage to that very fragile trust that communities have begun to build back with the scientific community.

Given these stakes, traditional approaches to benefit that center on the advancement of scientific knowledge seemed to fall short for many researchers at the front lines of PMR. Consequently, as we explore in the following two sections, some of our informants described ways that they already were negotiating both clinical and extra-clinical benefits for their participants in their day-to-day work and a desire to amplify these practices. Others described ways in which they imagined the research enterprise could or should be redesigned to benefit recruited communities more directly.

Negotiating Clinical Care for Research Participants

Regarding direct clinical benefits, multiple interviewees expressed a personal commitment to helping participants access needed medical care, even while this was not a formal component of their study protocols. Their reflections reveal an understanding of these individuals, first, as situated precariously within the unequal US healthcare system and, second, as research participants. Our interviewees described experiencing tension between their role in the research study and their role as clinical providers, often referring to research participants as their “patients.”

For example, one genetic counselor, a white woman, emphasized she was the only available prenatal genetic counselor in the economically depressed region where she worked. She described the ethically challenging negotiations she experienced when her boundaries as a member of the research staff did not align with her professional commitments to the provision of standard clinical care in this resource-limited context:

I think a hard thing for me on this study was I had my years of clinical experience and it can be very challenging changing those hats. I had a lot of conflict the first year of the study where I got really upset and scared because I didn’t want to violate IRB and drift away from what I was supposed to be doing [for the study] – but also, at the end of the day, my patient is so important and I didn’t want them to lose [out] on an opportunity for information and so I just have to make sure that they get the follow-up that they need, and there are some safety nets built in so I can do it on the back end.

She described having a conversation with a participant where she discussed the research results as a study staff member. Afterward, she literally exited, turned around, and then re-entered the room, explaining that she was now “wearing her clinical hat” to discuss additional medical considerations.

Research staff linked to a second PMR consortium pointed to the importance of the medical tests that the study provided for participants, pointing to this as a clear benefit of participation they widely promoted. A long-time staff member, a Black woman, explained, “there have been persons who actually found out that they had certain things (i.e., medical conditions) and were really grateful because it saved their lives.” She added that research staff were committed to returning results as quickly as possible to participants and would return those that they could the same day:

Just in case something shows up that you can let them be aware of that day, instead of waiting 3 weeks before someone at the reading center actually reads it. We try to be a little bit proactive on things that we can be.

However, this study’s commitment went further than the timely return of research results. She explained a social worker was brought onto the study’s staff to help respond to the needs of uninsured participants requiring follow-up care:

There were people who may not have been able to have access to a physician, so we assisted them with that. There are some community clinics that do see low-income participants there are those clinics available. That’s the purpose of the social worker, trying to find some means that they can actually see a physician.

This study leveraged existing community resources to help ensure the accessibility of follow-up care. The same research staff member explained that the social worker was also attentive to non-medical needs. Food security, for example, had come onto the study staff’s radar as a key issue impacting their participants. Indeed, as we discuss below, frontline interactions with participants often led to a concern over unmet material and psychosocial needs across the three consortia we studied.

Confronting Material and Psychosocial Benefits

Multiple interviewees encountered participant needs that went beyond clinical care (e.g., transportation and poor neighborhood conditions) and described grappling with how to respond. One research coordinator we interviewed, a Black man, said he had accepted a job with his PMR study out of a desire to work for the wellbeing of the low-income and historically medically underserved community in which he lived. Yet he found himself deeply frustrated by what he perceived as a mismatch between the community members’ needs and concerns and what the study offered. He explained:

Sometimes I think that there’s some confusion about really understanding what this population kind of is going through and what that looks like. I wish that there was more of a view to look at research as service. Just being able to give information [about] other things that could be helpful in the community like in their lives or what they actually might need or be able to kind of steer them in the right direction for some of these other needs.

The same research coordinator continued:

I mean, there are a whole host of life events, life decisions, things that they have to deal with. Like immediate things: How am I gonna pay the rent? Do I have enough money for groceries? I mean, just 2 weeks ago I had someone yell at me and [say], “You’re out here passing out flyers. You know, why don’t you call about the housing conditions in this building that you guys are out in front of? How is this helping?”

He described uncomfortable interactions with potential enrollees when he had only inadequate responses to what he felt were legitimate questions about the utility and benefit of the research study for community members. Another research staff member working on a different study, a woman who identified as Hispanic and white, described feeling a moral responsibility to address participants’ immediate material needs and being given the latitude to respond by her supervisor. She explained:

She’s the one who will allow us to foster these things. She’s not in the clinic, so obviously, when we come up to her and we tell her that this is what we’re experiencing, she really will give us the space to figure out a plan for action for those people or a way to assist them.

She said that in many cases, she found the incentive payment that the study offered to participants felt insufficient:

People who really need it, they’re always kind of like, “This isn’t enough for what I’m giving you.” And in those times, I wish that I could help them more because I know what that’s like. They’re not just there for altruistic reasons, they’re there to [get money in order to] have food or something.”

For our interviewees, the onset of the COVID-19 pandemic brought into even sharper relief the range of unmet material needs of enrolled and potential participants. The same staff member described her team’s desire to provide direct benefits to the communities they were engaging in response to the crisis:

We’re really thinking about communities [in our region] that have been really affected, like the Latinx community. They’ve been highly affected by COVID, and so we’re trying to design either something really easy for them to see where they could find help, food banks or clinics in their area, or any type of mental health resource. When you’re in the clinic, you can really foster a relationship with them, and if they need help, they’ll be very open to you, from my experience.

Similarly, another staff member, a white woman from a different study, explained that as the COVID-19 pandemic progressed, her team realized they could no longer conduct retention activities. Instead, their check-in telephone calls to participants became longer conversations in which they dedicated time to listening to the experiences of participants who were sheltering in place and others who were required to work in-person as “essential workers.” She explained:

We were able to talk to our participants during an incredibly harrowing time, to show our humanity. And all of us feel so passionate about our participants. We all feel so responsible for keeping those participants engaged. And so being able to make those phone calls was huge.

While she emphasized that her team members were not trained as mental health or social workers, she recognized that giving space for listening to and acknowledging the broader in which participants were living felt necessary. We found that an understanding of this kind of psychosocial need was common; it was by no means limited to the context of the pandemic. Research staff from a different consortium reported that periodic telephone calls and visits to participants carried out to collect longitudinal data often involved, in practice, far more intimacy than was contemplated by the research protocol. In one example, a research staff member, a Black woman who was also a participant in the study she worked for, described going to a participant’s house on a Sunday after repeatedly failing to reach her by phone. When she arrived, the woman invited the staff member into her home:

I ended up being there a long time because she needed to talk. She didn’t know me. She could confide in me, and I could listen. I was able to listen to her, and she could get her feelings out. I gave her what she needed.

The same staff member said that some participants, who were also her community members, asked her to pray for them and she did. She explained:

We’re not supposed to do religious things, but when you’re dealing with your people, you know that means a lot to them. And, I’m being perfectly frank, like I told my boss, if they asked me to pray for them, I do it right then and there.

At the front lines, our interviewees’ often impromptu negotiations in response to unmet material and psychosocial needs reflect the lack of clear guidelines around a broader range of benefits that many PMR researchers consider to be necessary on the ground. In the absence of clearer policy regarding benefit, frontline research staff experience the moral burden of negotiating research protocols themselves – as in the case of the research staff member who prays for her participants although she believes she is not supposed to – or they carry the frustration of inaction.

Discussion

Precision medicine researchers are increasingly engaging minoritized and under-resourced communities for inclusion in research studies to fulfill diversity goals. Traditionally neglected and/or exploited by the biomedical research enterprise, these communities are being targeted to redress existing inequities in genomic databases and to support equity in the future translation of precision medicine innovations. Despite these intentions and the existing guidance provided by institutionally approved ethics protocols, our findings indicate that many staff and investigators take issue with and sometimes actively negotiate, at the front lines of research practice, what is owed to participants and their communities in exchange for the data they provide. Here, not only is the divide between research and care challenged, but the very framing of benefit comes under scrutiny.

Like critics who have elsewhere contended with the “unsure promise” offered by PMR [48, p. 71], our informants shared that when they told potential enrollees that the objective of PMR was to eventually improve prevention, treatment, and ultimately health outcomes in the future, this promise felt inadequate for two reasons. First, researchers recognized the fraught experiences of many members of these communities with local health systems, including unequal and unaffordable access to health products and services, as well as experiences of discrimination. Second, they recognized more immediate unmet needs of the individuals they encountered, including access to medical attention, to food, and to mental health support.

Here, critical tensions over the temporal nature of benefit become clear. While standard ethics guidelines accept the uncertain “promise” and potential future benefits of PMR as sufficient, frontline researchers grapple with the contrast between the promissory nature of future benefits and the highly constrained (and sometimes nonexistent) resources available to address immediate needs in the present.

Researchers also grapple with the reality that participation is required in the present for underrepresented and minoritized groups to equitably attain the future promises of PMR, while historical evidence suggests little reason for faith that such promises will be fulfilled. Such promises of dramatic improvements in health are woefully complicated by the realities of the stratified US healthcare system, disproportionately structured by private interests [49]. Skepticism – and even “biodefection” (i.e., informed refusal to participate in biotechnological projects) [50] – among members of minoritized communities makes sense when they have rarely witnessed the political will necessary to improve basic healthcare or otherwise support the health and wellbeing of their communities. Our findings indicate that many PMR staff are well aware of these politics and history.

Some researchers found themselves unequipped to respond to the immediate needs of research participants and called for the establishment of mechanisms to more closely integrate research with service in the communities where they were working. Others conveyed that they had some tools, albeit limited, at their disposal with which to respond on an ad hoc basis to immediate needs. For example, where a full-time social worker was employed to work with participants who required services outside the scope of the study. Others recounted drawing on their personal emotional and spiritual resources to help meet participants’ psychosocial needs – performing a form of often unrecognized labor sociologists have described as “care work” [51, 52]. Importantly, none described the development of structured safety nets to follow-up with participants to ensure their basic needs were being met.

Beyond the individuals they were recruiting or had enrolled, researchers also indicated that community-level benefits were important to consider, shifting the scale of potential benefits well beyond the return of individual-level research results, which is currently accepted as best practice within US-based PMR. Indeed, some informants shared their desire to work more closely with policymakers to implement research findings. However, they recognized that doing so would divert time and energy away from the requirements of career progression and tenure and promotion. Others raised doubts that the foreseeable innovations PMR is likely to deliver could truly impact health in the communities they were targeting in the absence of major structural reforms.

It is critical to recognize that this moral distress warrants systematic redress not by individual researchers, but by the broader research infrastructure. Like Wadmann and Hoeyer [29], who have studied the “moral frictions” that arise in the everyday work of clinical trials, we view the frontline tensions reported here as potentially generative – likely to produce innovative approaches and spur necessary action – rather than debilitating for the research enterprise. In this case, our informants’ negotiations and frustrations point to potential reforms to research practice.

The perspectives presented here indicate how research that prioritizes maximizing benefits may also foster deeper engagement in reconceptualizing the research/care relationship – not as a divide – in partnership with those groups that are underserved by both, in aspiring toward more equitable inclusion of diverse individuals and communities within the PMR enterprise. For example, a significant shift in PMRs approach to benefit through the explicit integration of research with care in the form of health and social services to vulnerable communities – as one of our interviewees envisioned – may be perceived initially as a radical change. However, we emphasize that such alternative approaches are well within the scope of conversations already taking place globally with regard to biomedical research justice, including initiatives to provide ancillary care, fair benefits, and benefit sharing [31, 32]. These initiatives are grounded within justice-driven frameworks that directly account for the stark social, economic, and health inequalities raised by internationally funded research carried out in developing countries. As US-based researchers deepen their engagement with vulnerable communities within the USA in response to diversity mandates, these global conversations offer useful resources with which to begin rethinking approaches to benefit and responsibility.

Finally, given the experiences of our interviewees, we contend that the field of precision medicine is more likely to meet its goals for inclusion if these debates are moved from the front lines to the center of institutional power within the field. It is necessary that funders, policymakers, and IRB representatives push beyond the present focus on “return of results” to PMR research participants. Now is the time to confront tough questions, such under what circumstances it might be appropriate to forgo research in order to funnel resources into more pressing healthcare needs and whether nationally funded large-scale research programs can be reconciled with our market-based healthcare system. Ultimately, a formal recalibration of how benefit and responsibility are conceptualized and allocated within the US research enterprise is not only possible but also a necessary step on the path toward improving health equity in the USA.

Limitations

Given our focus on researchers linked to five PMR studies, our sample may not be representative of the viewpoints of all those involved in PMR. We also did not assess the viewpoints of PMR study participants themselves. Finally, additional analysis is necessary to assess whether similar tensions around benefit are evident in other areas of biomedical research beyond PMR, a field in which medical and public health benefit remains a particularly elusive promise of the distant future.

Acknowledgments

We thank the participants of this study, who generously shared their time and insights. We also acknowledge the contributions of team members from the Ethics of Inclusion study, from which these data were drawn, and Larissa Saco, who reviewed a previous draft of this article.

Statement of Ethics

The study was approved by the University of California, San Francisco Institutional Review Board (IRB#: 18-25971) and Columbia University. All participants provided informed consent to participate. We obtained verbal informed consent for all observations and written informed consent for all interviews. The requirement to obtain verbal informed consent for observations was specifically approved by both Institutional Review Boards.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This work was supported by the National Institutes of Health (R01-HG010330).

Author Contributions

Study designed by J.S., S.L., A.S., and S.M.F. Interviews conducted by J.S., S.L., E.V., M.J., M.B., N.F., C.M., and S.M.F. Data analysis performed by all authors. Literature review conducted by E.V., N.F., and C.M. Manuscript drafted and revised by E.V., N.F., C.M., M.J., J.S., and S.L.

Funding Statement

This work was supported by the National Institutes of Health (R01-HG010330).

Data Availability Statement

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants. Further inquiries regarding data availability may be directed to Sandra Soo-Jin Lee, PhD (sandra.lee@columbia.edu).