Changing the Conversation about The Ethics of Genomics and Health Disparities Research with American Indian and Alaska Native Communities: A Report from the Field

Summary:

“Changing the conversation”* around genomic research with U.S. tribal communities may lead to new pathways to address persistent health disparities. Restoring trustworthiness between researchers and communities entails a willingness to listen to Indigenous voices, being flexible, and refining existing policies and frameworks to adapt to communities’ needs.

The National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) recently reiterated its commitment “to fund, conduct, and encourage diversity in biomedical research to build a strong foundation for genomic medicine.”^1[p.181] This renewed commitment is, in part, a response to recent findings that genomic research databases are lacking in representation from diverse populations,² which hinders their utility in genomic research on health disparities across these populations. Although it is widely acknowledged that social, economic, cultural, and political factors are determinants of health disparities, there is increasing recognition that health outcomes are the product of complex interactions between these factors, environmental exposures, and inherited characteristics.³ This suggests that more representative genomic variation data from diverse populations are needed in order to understand genomic contributions to health and disease, and to apply this knowledge to clinical practice. Some have argued that “inequities in the amount and quality of genetic and genomic data generated for various human populations have the potential to exacerbate [emphasis added] existing health disparities as genetic discoveries are translated into clinical and public health interventions.”^4[p.502] Indeed, if genomics is to become part of the delivery of clinical care, it is important to ensure that the populations who experience a disproportionate burden of disease are not excluded from the research that informs this care.

Yet at least some of the populations whose data have not been included in genomic research databases are reluctant to allow their data to be collected, stored, and used for broad, open-ended genomic research. This is especially true of American Indian and Alaska Native (AI/AN) tribes who have been harmed by instances of unethical or “helicopter” research, defined as “[t]he failure to return results or focus on community benefit … [whereby] the researcher drops into the community, extracts data, and is never heard from again, or at best provides information about the study in technical language that is unfamiliar to most in the community.”^5[p.343] Such research is particularly problematic when it deals with topics that are stigmatizing to tribal Nations; it has increased AI/AN tribes’ distrust of the research enterprise as a whole, and of genomic research in particular.^6,7

There is a conflict, therefore, between the desire to diversify participation in genomic research and the factors that limit the willingness of some populations to participate in such research. The incorrect conclusion, however, is that it is not possible to conduct genomic research with these populations. Bioethicists who work alongside researchers (including myself), among others, ought to be concerned about such a conclusion, which would effectively exclude entire populations from receiving benefits from the public investment in genomic research. Further, it is a misconception that tribal communities are wholly opposed to genomic research participation;⁸ indeed, tribal populations have voiced awareness of the potential benefits of health and genomic research to their communities. Navajo Nation’s 2002 moratorium on genetic research includes provisions to work towards creating a policy, with education and thoughtful engagement with the Nation’s citizens, that allows genetic research to proceed.⁹ Efforts to develop a Navajo genetic research policy that will replace the moratorium are underway.¹⁰ Examples of successful collaborations between genomic researchers and tribal communities have emerged, such as a pharmacogenomic study of warfarin that predicted a lower average dose requirement among AI/AN populations in Alaska than in other U.S. populations.¹¹ It would be helpful to identify factors that distinguish successful research collaborations such as this one from unethical examples of the past.

There are many components of an approach to increase inclusion and engagement of underrepresented populations in genomic research. A roundtable discussion hosted by NHGRI in 2015 articulated the following recommendations:

1. Provide leadership for the field of genomics in promoting in health disparities research using genomic methods.

2. Examine institutional factors that impede greater inclusion of underrepresented populations in genomics research.

3. Promote the incorporation of environmental data into genomics studies.

4. Promote comprehensive strategies for analysis of existing biospecimens from underrepresented populations.

5. Support sustained community engagement and community-based participatory research. (available at: https://www.genome.gov/pages/about/nachgr/february2016agendadocuments/2015_09_16_roundtable_report_final.pdf)

I interpret the second and fifth recommendations as directives to examine the ethical oversight of genomic research with underrepresented populations, particularly given that the extant federal regulatory framework for ethical review was insufficient to prevent the harms that befell AI/AN communities in previous genetic research. In their analysis of the Havasupai Indian Tribe v. Arizona Board of Regents case¹² and other examples of problematic genetic research with tribal populations, Goering and colleagues articulate arguments for “responsive justice” to address shortcomings in the ethical oversight of such research: “[A] profound disconnect exists between common academic research practices and legitimate community expectations, and justice requires this gap to be bridged.”^13[p.44] Addressing this disconnect requires us to transform research to be more sensitive to the needs of tribal communities.

The framework of community-based participatory research (CBPR) partially addresses this call for responsive justice in the context of genomic research.¹⁴ Within CBPR, where there is emerging attention to the oversight and governance of research within diverse populations,¹⁵ I have noted at least three approaches with the potential to bridge the gap between genomic researchers and tribal populations: (1) the increased presence and involvement of tribal-based institutional review boards (IRBs) in the oversight of genomic research with tribal populations, (2) flexibility in the application of federal research regulations and policies, and (3) refinement of existing ethical frameworks that guide the conduct of such research.

First, tribal-based IRBs provide a mechanism for AI/AN tribes to participate in the oversight of research that takes place within their communities, allowing them to “control new health science research, set their own research agenda, and protect their people in the same spirit as has been accomplished through the perpetuation of sovereignty rights.”^16[p.2161] Tribal IRBs have developed policies that address the scope of consent, data sharing, and other features of genetic research to ensure that it is conducted in a manner consistent with the values of the tribes that they serve. (See e.g., the document available at http://www.ncai.org/policy-research-center/events/ChickasawIRBSlides.pdf). Part of the mission of the NHGRI Bioethics Core, which I direct, is to support capacity-building in the areas of IRB review and research ethics oversight. Recently, in collaboration with the NIH Clinical Center’s Department of Bioethics, we turned our focus to expanding training and educational programs for tribal-focused IRBs, given their pivotal role in allowing beneficial research to be conducted ethically within tribal communities. (See e.g., the document available at https://www.primr.org/webinars/sept2016/ and https://www.bioethics.nih.gov/alumni/irb-training.shtml.)

Second, in 2016, tribal leaders issued an American Indian and Alaska Native Cultural Wisdom Declaration that urged federal funding agencies to “[m]odify your requirements to fit the relevant traditional tribal paradigm or allow room for flexibility when evaluating proposals submitted by American Indian and Alaska Native tribal nations.”^17[p.6] Although this document focused on behavioral health, the recommendations are applicable to the broader research context, including genomics research. An example of a constructive modification to research regulations appears in the recent revisions to the U.S. regulations that govern the ethical review of human research, also known as the Common Rule.¹⁸ Informed by consultation and community outreach,¹⁹ the new rule includes an acknowledgement of the sovereignty of tribal nations to pass regulations that provide additional protections beyond the provisions of the Common Rule.²⁰ As I have stated, this revision will promote respect for AI/AN communities by calling attention to the importance of tribal IRBs, laws, and policies that are crafted “both to safeguard the unique values and cultural heritage of AI/AN communities and to hold researchers accountable for interacting with these communities in a trustworthy, transparent manner.”^21[p61–62] Flexibilities in other federal research policies, e.g., related to genomic data-sharing (see the document available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html) and single IRB review (see the document available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-094.html) as they are applied to tribal research are also developments that hold promise for respecting tribal perspectives in the conduct of research.

Finally, I call attention to nascent efforts to refine the ethical framework that guides the conduct of research with tribal communities, such as a recent publication that proposes an ethical framework, borne out of engagement with tribal communities to discover the values that they prioritize in the ethical conduct of research.²² This structure, which was developed by a team of Indigenous researchers and is specific to the context of genomic research with Indigenous communities, includes concepts such as reciprocity, transparency, and cultural competency that are not explicit in the existing federal regulatory framework. Such an approach will have relevance to Indigenous communities globally, adding to an emerging body of scholarship, policies, and ethical frameworks that have the potential to advance collaborative genomic research programs by prioritizing respect for communities and paying attention to Indigenous voices.

Each of these developments represents a departure from the usual concerns about the ethics of genomic research. To achieve responsive justice,¹³ those of us who see the need to diversify participation in genomic research as part of a larger strategy to understand the complex causes of human disease must expand our thinking beyond the familiar ethical frameworks and mechanisms by which we oversee the conduct of research. We must help to change the conversation.