Precision Medicine Research with American Indian and Alaska Native Communities: Results of a Deliberative Engagement with Tribal Leaders

Abstract

Purpose.

Amid calls for greater diversity in precision medicine research, the perspectives of Indigenous people, have been underexplored. Our goals were to understand Tribal leaders’ views regarding the potential benefits and risks of such research, explore its priority for their communities, and identify the policies and safeguards they consider essential. This paper reports on participants’ perspectives regarding governance and policy; stewardship and sharing of information and biospecimens; and informed consent.

Methods.

Following informal local dialogs with 21 Tribal leaders, we convened a 2.5-day deliberation with Tribal leaders (N=10) in Anchorage, Alaska in June 2019, using a combination of small group and plenary discussion, ranking, and voting exercises to explore perspectives on precision medicine research.

Results.

Tribal sovereignty was central to participants’ ideas about precision medicine research. Although views were generally positive, provided that appropriate controls are in place, some kinds of research were deemed unacceptable, and the collection of certain biospecimens was rejected by some participants. Differences were observed regarding the acceptability of broad consent.

Conclusion.

Tribal leaders in this study were generally supportive of precision medicine research, with the caveat that Tribal oversight is essential to the establishment of research repositories and the conduct of research involving Indigenous participants.

Introduction

If precision medicine research is to improve healthcare for all, people from all walks of life must participate. Worldwide, Indigenous populations bear a disproportionate burden of ill health, due in large part to social determinants,¹ and are underrepresented in research, including precision medicine research.² In the United States, lower rates of American Indian and Alaska Native (AIAN) research participation reflect a history of mistreatment by outsiders that has generated lasting mistrust.^3,4 AIAN Tribes are sovereign nations with an inherent right to self-determination, including deciding whether and how health research may be conducted.⁵

How best to operationalize respect for both Tribal authority and individual autonomy of Tribal members in precision medicine research is undetermined; and human subjects regulations emphasize protecting individuals, rather than avoiding group harms.⁶ Some AIAN communities are willing to participate in precision medicine research if appropriate safeguards and governance are established.^7–11 What those protections entail, under what circumstances they apply, and where the requirements of particular communities may differ have not been specified. We convened a deliberation with Tribal leaders from three regions in Alaska and Montana to consider three topics: stewardship of research information and biospecimens; return of research results; and how precision medicine research may align with Tribal health priorities.

Democratic deliberation convenes diverse people for in-depth discussion of value-laden issues in search of collective solutions.^12,13 It differs from other forms of public engagement, such as surveys and focus groups, by yielding well-informed and carefully considered opinions that are civic-minded.¹⁴ Although democratic deliberation is increasingly used to gather informed public input on important social issues, its use with Tribal communities is rare. Deliberations have been conducted that include Indigenous people, but we know of only one other study that involved exclusively Indigenous people.¹⁵

A deliberative approach to engaging Tribal leaders was well-suited to this project because deliberation is purpose-built for issues that involve conflicting values, controversy, low trust in government, and shared challenges or community or societal goods.¹⁶ All of these apply to questions about the potential relevance and use of precision medicine research with Tribal communities. Second, deliberation’s collectivist orientation—’what ought we to do about this shared challenge?’—aligns with Tribal leaders’ responsibilities to protect their people, cultures, and nations. Third, deliberative democratic theory and practice emphasize the inclusion of voices that have been excluded from mainstream decision-making processes. Finally, in response to critiques that, despite its egalitarian intentions, deliberation’s emphasis on reason-giving, argumentation, and consensus tends to discount minority voices,^17–19 deliberative theory and practice have evolved to accommodate diverse speech forms, self-interest and emotion, disagreement), and enclave deliberation (wherein deliberants share one or more important characteristics).^12,20–22 These expanded frameworks and tools have created opportunities for innovative deliberation designs. A full description of the deliberative methodology and process outcomes for this project is under review.

Materials and Methods

Design, setting, and participants

The deliberation was the central research activity of a National Human Genome Research Institute grant, “Community-Engaged Research toward Precision Medicine with AIAN People,” built on more than a decade of collaboration within the Northwest-Alaska Pharmacogenomics Research Network (NWA-PGRN).²³ The NWA-PGRN involves a partnership among three regions in Alaska and Montana, their respective Tribal health departments/organizations, and investigators at the University of Washington, Southcentral Foundation (SCF), Oregon Health and Science University (OHSU), and the University of Montana (UM). Together, the Tribal health departments/organizations – SCF, the Yukon-Kuskokwim Health Corporation (YKHC), and the Confederated Salish and Kootenai Tribes (CSKT) Tribal Health Department – serve more than 100 Tribes in Alaska and Montana (Table 1). The shared understanding and trust that have developed regarding the values and priorities of the participating AIAN communities facilitated use of this unfamiliar approach to engagement.

Table 1.

Community Partner Characteristics

Tribal Health Organization	Southcentral Foundation (SCF)	Yukon-Kuskokwim Health Corporation (YKHC)	Confederated Salish and Kootenai Tribes (CSKT)
Location	Southcentral Alaska; mixed urban and rural	Southwestern Alaska; rural	Northwestern Montana; rural
Population	~ 70,000 AIAN people in the Anchorage area and 55 outlying communities over 107,400 square miles	~23,000 residents in 58 federally recognized Tribes across 75,000 square miles	8,078 enrolled members; >5,000 on the Flathead Reservation covering ~2,000 square miles
Cultural group(s)	All 230+ Alaska Native Tribes and over 100 American Indian tribes	Yup’ik	• Bitterroot Salish • Upper Pend d’Oreille • Kootenai
Health system components	• Anchorage Native Primary Care Center • Benteh Nuutah Valley Native Primary Care Center • 13 village clinics• Alaska Native Medical Center*	• Regional hospital • 5 sub-regional clinics • 41 village clinics	• 7 health centers providing comprehensive health care services • 3 fitness centers

^*co-managed with the Alaska Native Tribal Health Consortium

The deliberation was preceded by local dialogs in Bethel and Anchorage, Alaska, and Polson, Montana in April – May 2019. We used a convenience sampling frame to recruit AIAN adults serving in leadership positions within their respective region (Yukon-Kuskokwim Delta, SCF, and CSKT). We aimed to recruit 3–5 Tribal leaders from each region to participate in each local dialog, with the goal of convening a cross-site deliberation of 12–15 Tribal leaders, a common size for face-to-face deliberations. Seven leaders from each region (N=21) participated in the dialogs, where they were introduced to the idea of precision medicine research and began to familiarize themselves with relevant terms and concepts, discuss the issues amongst themselves, and situate this information within their own Tribal contexts. The dialogs were a culturally appropriate adaptation of the printed briefing materials typically sent to participants in advance of deliberations.

Ten Tribal leaders participated in the deliberation: 4 from the YK Delta in southwest Alaska; 3 from SCF in Anchorage, Alaska; and 3 CSKT representatives from the Flathead Reservation in western Montana. Due to competing priorities, the CSKT dialog participants were unable to attend the deliberation; members of the Community Pharmacogenetics Advisory Council, who were familiar with relevant concepts, attended in their stead. Deliberants represented a range of roles, including formal leadership or advisory positions on Tribal Councils or other decision-making bodies, and all identified as Indigenous. Seven women and three men between the ages of 33 and 70 participated; eight participants were 60 years of age or older. All had at least a high school education. Seven had a 4-year college degree and four had education beyond a baccalaureate degree.

The deliberation design used plenary and small-group discussions and voting and ranking exercises to deepen individual learning, promote full participation, create opportunities for shifts in views, and encourage cross-site conversation and learning. Mixed small groups were used to discuss two topics: Tribal health priorities and return of results. For data stewardship, deliberants were grouped by region, because of the salience of particular governance structures, sovereignty issues, and varied histories with research.

Although consensus is sometimes the overarching goal of deliberations, we aimed to identify areas of agreement and disagreement ^12,13,24 to avoid silencing non-dominant perspectives, encourage a wide-ranging discussion, and respect the sovereignty and heterogeneity of Tribal communities. Moreover, techniques such as voting and ranking exercises made the research team and deliberants aware in real time where there was, and was not, common ground. Another central feature of deliberation is that exposure to new information and discussion with others may lead participants to shift their perspectives. Whether or not this occurs, the duration, intensity, and iterative nature of deliberations provide participants with a much deeper understanding of viewpoints that differ from their own.^12,13 As we discuss below, this immersive discussion enabled Tribal leaders to learn from each other and explore the translation of community values into viable policy options.^14,25

Data collection

The deliberation was held June 13 –15, 2019, on the Alaska Native Medical Center campus in Anchorage, Alaska. It was moderated by two study team members who are bioethicists and experienced facilitators (EB, SBT). Lead researchers from each region (BBB, VYH, SEH, ELW) were present to observe and provide technical assistance, with additional staff (RBW) on hand to assist with logistics. We audio-recorded and transcribed deliberations, collected voting sheets and worksheets, and took digital photos of whiteboard and flipchart notes.

For the stewardship portion of the deliberation, SBT provided a review of the ideas and questions that surfaced in the local dialogs. We then invited deliberants to break into regionally defined small groups to discuss data stewardship, guided by a written worksheet (Table 2). While the deliberants conversed, the facilitators drew a table on the whiteboard with the 10 topic areas as rows and the three regions as columns. We asked each small group to hand in their worksheet, which the facilitators transferred to the whiteboard during a break. When we reconvened, a deliberant reported out from each small group. This was followed by open discussion, with deliberants and the facilitators asking clarifying questions. Deliberants compared notes with their counterparts from other regions, identifying commonalities as well as ideas and structures not currently present in their respective regions; using stickers, they tagged the ideas they endorsed from other groups..

Table 2.

Worksheet: Design a Data Stewardship Model for Your Community

TOPIC	QUESTIONS TO CONSIDER
MATERIALS COLLECTED	• What kinds of materials – data and/or biospecimens – should be collected and stored for future research? • Are there any materials that should be off limits?
SPECIAL PROTECTIONS	• Are there any kinds of information or biospecimens that need special protections? • Which ones?
OWNERSHIP	• Who should own these resources once they are collected? • What does “ownership” mean to you?
MANAGEMENT	• Who should be responsible for managing the electronic databases, freezers, etc.? • Who should pay for this?
SETTING POLICY	• Who should decide what the rules are about how data can be accessed, how it may be used (e.g. for what purposes)?
CONTROLLING ACCESS	• Who should review incoming requests for information and biorepository access to make sure the research is beneficial to participants and their communities and that the researchers are trustworthy?
WHO CAN ACCESS DATA AND BIOSPECIMENS	• What are the criteria for researchers: academic researchers, government researchers, drug company, insurance companies, Tribal Health organization, anyone?
ALLOWABLE RESEARCH QUESTIONS	• Are there any kinds of research questions that should NOT be allowed? • If so, what are examples?
COMMUNITY CONSENT	• Must there be community consent and Tribal approval for individual community members to participate? • What should community consent look like? • What about Tribal members who live in urban areas and/or off Reservation lands?
INDIVIDUAL INFORMED CONSENT	• Is broad consent – permission for all future research uses – OK? • If not, what should be done instead?

Data analysis

SBT consolidated the small-group worksheets into a single table to gain an overview of how ideas coalesced or diverged by topic. This was reviewed by VYH, who added additional content from her notes and the transcripts. The consolidated table was checked against the photos of the whiteboard. SBT then reviewed the relevant portions of the transcripts, together with her notes, to create a more detailed picture. We then performed a descriptive qualitative analysis, relying on a combination of deductive coding (based on the worksheet topics) and inductive coding (identifying additional themes that emerged from the discussion).²⁶ Where we report consensus and divergence, these were based on the final conclusions of the deliberants, rather than tracing changes in participants’ discourse or views throughout the 2.5 days.²⁷ SBT drafted the initial results, with review and amendment from VYH and EB. All authors were involved in a final review of results.

Results

Governance and policy

All deliberants agreed that the information and biospecimens contained in a precision medicine biorepository are the property of the community, with oversight properly delegated to the relevant Tribal government. Deliberants expressed responsibility for promoting the interests of individual participants as well as the community, equating “control” with decision-making authority over data and biospecimens. Asked who should have responsibility for policy-setting (e.g., determining access to a biorepository containing information about Tribal members), deliberants unanimously responded that such decisions belong to the community, via established bodies such as the Tribal Council, Tribal IRB, and/or ethics review board. One of the SCF leaders said:

It’s our opinion that the Tribes are the ultimate authority, and who gives the Tribe authority are the individuals [in the community]. But if the individuals tell the Tribe “no,” then the Tribe needs to tell everybody else not just “no,” but “hell no.” Because it all comes down, when we look at this genome project, it has major, major ramifications associated with genocide, and so that’s my concern.

All of the groups felt that a multi-level process would be appropriate for the review of requests for information and biospecimens. The YK Dela group said that, for their region, the local Tribal Council and YKHC should review, as well as the IRB of the academic researchers’ institution. The CSKT group said that primary responsibility should rest with the Tribal Council, the IRB of the Tribally chartered Salish Kootenai College (SKC), and the Séliš-Ql̓ispé and Kootenai Culture Committees, and that a Tribal ethics committee could also be established. The SCF group said that both Tribal review and Alaska Area IRB review would be required. SCF deliberants also said that access should be strictly controlled by the participating community, through its established bodies, and that access to or use of data falling outside the original terms consented to by participants would require additional approvals and participant consent.

With respect to biorepository access, we asked whether there were any particular classes of possible requestors who should not be granted access to Tribal members’ data or biospecimens. Deliberants did not identify any category that should be barred from access, but the CSKT group drew a distinction between university researchers and commercial entities:

While we want to give our samples to pharmaceutical companies so that they can make better medication for our people . . . they’re going to make us pay for that information. They definitely should not [laughs] be having access to us because they’re just going to take our information and turn it around and make money off it, versus academically, [university researchers] come in, they’re going to do the research, but also give us the information back free, versus paying for it.

Deliberants agreed that, subject to the approval of the relevant Tribal ethics committee/IRB, academic researchers and Tribal health leadership should have access. SCF and YK Delta leaders stressed that, in their regions, it would never be acceptable for researchers to approach a community directly: researchers must work through the Tribal health agency.

We also asked whether there were kinds of research that ought not be permitted under any circumstances or that would require special protections. Leaders from CSKT stated that neither research on “lineage” nor broader research on “origins and evolution” should be permitted, with one leader commenting, “We are here, we were put here, but you don’t need to figure out the trace to . . . the beginning point.” Leaders from the YK Delta agreed, noting that the information and materials collected for use in precision medicine research should be used for health research only, and not for other purposes. A member of the SCF group reported, “We ended up saying everything needed special protection because it defines us, but the one that we felt a little more protective of was anything that would define us as a people or try to say that this Tribe or this group . . . . but really, everything needs special protection, especially when it’s identifying us as Indigenous.”

Stewardship of information and biospecimens

We asked whether there were particular kinds of information or biospecimens that ought not be used for precision medicine research. Leaders from all groups said that the collection and storage of blood was acceptable provided that samples were obtained, stored, and disposed of appropriately. The CSKT group said that, across the three Tribes that make up the Confederated Tribes, hair and other bodily tissues generally should not be used, explaining, “If something leaves our body, we want to know what happens to it . . . because a lot of our belief system is, we cannot move forward to the next life without all of our pieces . . . . So, we really are just thinking blood is about the only material that we would be ok with letting go of.” Later in the discussion, a CSKT leader added that the potential for an ill-intentioned person to use such materials “to put bad medicine on you” is another source of concern. Leaders from all three regions considered that the collection of organs (“body parts”) for use in health research should not be allowed; the SCF group clarified that organ donation in the clinical setting is permissible. The SCF group also commented that data collection practices should be determined on a case-by-case basis.

Deliberants expressed interest and, in some cases, concern about how information and materials would be stored and whether, when, and in what manner they would be destroyed or returned. Deliberants spoke of “taking care of” these resources. Leaders from the YK Delta focused on privacy concerns, identifying DNA, fingerprints, and personal identifiers as requiring extra protections against loss of confidentiality. CSKT leaders said that if Tribal permission had been granted to collect specimens other than blood, ceremonial treatment to restore or dispose of these materials may be needed when the research is completed.

Regarding oversight of the ongoing operations of a biorepository (e.g., managing databases, facilities, equipment) views diverged widely. Participants from the YK Delta said that researchers should manage and pay for the upkeep of the repository, under Tribal oversight. The CSKT group expressed a desire to keep these materials on Tribal land, identifying the SKC as a possible home for research information and biospecimens. They thought that researchers should pay SKC for these services, and suggested that this approach would also have the benefit of giving students “experience in handling sacred samples, and then also they gain knowledge from it, too.” The SCF group thought that SCF should hold responsibility – and thus control – for biobank operations, and that the costs should be shared by the Tribal health agency, researchers, and funders.

Informed consent

In addition to review by a Tribal IRB or ethics oversight board, research with Tribal communities often requires some form of community consent. The CSKT group spoke of “layers of protection,” explaining that community consent is not inconsistent with individual autonomy: “It’s not ownership, like the Tribe owns me. I own myself, but then the Tribe, as a group, we’re trying to protect everybody within the Tribe. We have our warriors, our men, our women, and our children. So, we have these layers.” For the CSKT, the Tribal Council reviews proposed studies and provides approval via vote; proposed research should then be reviewed by an ethics committee, if one were to be established, and by the SKC IRB. The importance of researchers investing the time and effort to present to Tribal Council was explained this way: “If a researcher wants to come in . . . then if they aren’t going to try really hard, then they don’t need to be doing research on our people . . . . If they can’t get up in front of Tribal Council, then they don’t need to be doing research on us.”

In the YK Delta, leaders said, individuals who live away from their home communities (e.g., in an urban setting) may decide for themselves, without Tribal Council input, whether to take part. For studies to be conducted in Tribal communities in the YK Delta, YK leaders stressed the importance of receiving approval to enter the community: one said, “If [researchers] want to come into our community to take some samples or [recruit for] the research, they would have to ask the community leaders if they can come in.” Similarly, one of the participants from SCF stated, “[T]here has to be an invitation of willingness by the Tribe for research to be a part of what . . . they want. You have to talk to the Tribes, and you have to be invited. And it’s not a phone call. It’s conversations, it’s relationship, it’s boots on the ground.” Researchers who wish to work in the SCF service area cannot directly approach Tribal communities; SCF serves as a central broker for all research review and consent for the communities it serves. They also said that, while individuals may choose to enroll in a study without Tribal/SCF permission, their participation should not be construed as representing the Tribe more generally:

We started talking about, could an individual consent if a Tribe said no? So, could I do it if my Tribe is in the Lower 48 [states], but could an individual say yes? And we said yes, but then you do not represent the Tribe. I mean, you can’t take away that I’m [Tribal affiliation], but I’m not representing my Tribe if I individually consent, and the Tribe hasn’t.

As health research, and precision medicine research in particular, is moving in the direction of broad consent we elicited deliberants’ views about one-time consent for future, undefined research purposes and studies. Deliberants felt that there is great uncertainty about the aims and parameters of future research. For example, a leader from SCF said, “[T]he future is unknown so far as technology and research and how the data will be used, because there will be other interests and other subjects to research to make our health a lot better.” Participants from SCF said that broad consent is acceptable, provided that clear and complete explanations are provided up front and participants fully understand what they are agreeing to. Leaders from the YK Delta and the CSKT, by contrast, said that broad consent was, in the words of one of the CSKT group, “a no-go.” The YK leaders said that individuals should have the opportunity to review proposed studies/research questions and decide whether they want to participate.

The YK Delta group indicated interest in allowing individual participants to retain some level of control over how their information could be used. Similarly, the SCF group stated that individuals should be able to select from a list of permission options: unlimited use, restricted use, do not contact me again, okay to contact me for future research. For all of the leaders, the most important issues were ensuring that (1) participants understand what they are signing up for, and (2) researchers abide by the terms of the original consent, and seek re-consent if there is any change in purpose or scope of the research.

Discussion

The paramount importance of Tribal sovereignty and self-determination in research was a common theme, notwithstanding substantial differences in Tribal governance structures. Sovereignty shapes the way Tribal leaders weigh the possible risks and benefits of research to their communities, as well as how individual community members make decisions about participation. Deliberants expressed appreciation for the opportunity to discuss these issues with their counterparts and learn from each other, and they said more such forums would be welcome.

Much precision medicine research, as currently envisioned, is premised on broad consent and widespread sharing of information and biospecimens. Broad consent was acceptable to leaders from one of the three study sites, raising the question of whether researchers’ definition of the range of activities that may be considered “health research” – the general term often used in broad consent procedures – aligns with communities’ and participants’ ideas. For example, while some researchers may categorize genetic research regarding human origins as health research, our study suggests such studies fail to align with Tribal definitions of health research. Until further research addresses this issue, broad consent that relies on such vague terminology is ethically problematic.²⁸ Consistent with prior research, we heard strong interest in tiered approaches that would allow Tribal leaders and individual participants to define how their information and specimens may be used in future studies.^29,30 These views may also be influenced by AIAN cultural norms of individual choice and noninterference.³¹

Group harm was a key consideration for deliberants. As has been described elsewhere, the regulatory system is geared to the protection of individual participants and does not yet satisfactorily address the issue of group harm.^6,23 For at least some Indigenous people, the prospect of genomic research is associated with the US government’s repeated attempts to eliminate them as peoples. The Office of Human Research Protections has begun to recognize the special standing of Tribal nations (e.g., by acknowledging that the new single IRB policy ought not supplant Tribal review³²), but more work remains to be done. For example, some Tribal communities have protested the recruitment of urban AIAN people into research studies as an “end run” around Tribal review protocols.³³

Consistent with research involving other Indigenous communities, deliberants were concerned with ownership, control, access, and use of Tribally derived information and biospecimens.^10,34,35 We noted an important difference between the way we and other investigators have framed the question of data stewardship and the way deliberants spoke about it. Our questions generally conceptualized the issues as related to the management of a scientific resource (e.g., what procedures are needed to maintain control and security). Deliberants’ primary emphasis, in contrast, was on “taking care of” the community’s resources and interests, including its identity as a community, its futurity (considering both future generations and the preservation of cultural and social integrity), and the wellbeing of its current members.^34,36 Moreover, deliberants’ concerns regarding ownership were not primarily about financial gain; rather, they related to protecting community interests and ensuring that communities would receive some tangible health benefit from participation. Consistent with Garrison and colleagues’ findings,¹⁰ deliberants wanted a high degree of Tribal engagement in ongoing governance and were unwilling to delegate oversight to outsiders, even trusted outsiders.

Variability in Tribal review was a recurring theme. Deliberants highlighted community and regional differences, in both local research capacity (e.g., availability of resources needed to manage research review) and interest in expanding capacity. Cultural differences in how communities view biospecimens must also be considered. Some communities view materials that are exempt from federal human subjects protections (e.g., hair samples) as sacred and still “of the person,” requiring special handling and/or ceremonial treatment.³⁷ Investigators must get to know the community, build relationships, and understand community members’ values and procedures, rather than presume that compliance with federal standards is sufficient. The burgeoning literature on participatory health research demonstrates positive effects on study participation and offers useful implementation guidance.^38–43

Our study had a few limitations. Deliberants’ views may not fully represent those of the communities where they live and work.⁴⁴ Tribal communities have their own unique histories, cultures, and governance, and these results are not generalizable to all Tribal communities. The lead investigators have a long history with the respective communities with which they work. While the lead investigators were not actively engaged in facilitation, it is possible their presence may have dampened questions or critique; conversely, it may have increased participants’ comfort.

Tribal leaders in this study expressed hope that the inclusion of genetics, environment, and lifestyle in precision medicine research will improve health of Indigenous peoples. Researchers must go beyond acknowledging Tribal sovereignty to enacting its recognition. For a start, this means inviting the engagement of Tribal leaders in defining the parameters of precision medicine research at the outset, and ensuring their involvement in the ongoing governance of the research and resulting repositories.

Data Availability

De-identified data will be made available upon request with the express permission of study participants and relevant Tribal review bodies.