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Precision medicine holds promise for improving health care by tailoring disease treatment and prevention efforts to the needs of individual patients. It also raises ethical questions related to equitable distribution of the benefits of precision medicine; data management, including the terms of data ownership, sharing, and security; and, the nature and extent of community engagement in and oversight of research. These questions are particularly salient for minoritized communities that have been harmed by unethical research practices and often deprived the full benefit of advances in medical science. Understanding the perspectives of these communities is essential to the design and conduct of ethical and effective precision medicine research. This study explored perspectives on the acceptability, feasibility, value, and benefits and harms of precision medicine research among Alaska Native and American Indian (ANAI) peoples. We conducted four focus groups with ANAI individuals who receive primary care from a Tribal health organization in Anchorage, Alaska. Participants were willing to engage in precision medicine research provided specific requirements were met. Research must be conducted by the Tribal health organization or another trusted partner, community health priorities must drive the research agenda, and researchers must employ robust data protections to guard against loss of data security and maintain control over data use and access. These requirements work collectively to ensure research benefits and respects Tribal sovereignty. These findings could help inform efforts to design and implement precision medicine research programs tailored to concerns of ANAI peoples., Competing Interests: Declarations. Consent to participate: Informed consent was obtained from all study participants. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

The cognitive interview process is a method to validate a survey instrument's face validity and enhance confidence in item interpretation, as well as a method to engage communities in the research process. Trained American Indian and Alaska Native (AIAN) interviewers conducted retrospective cognitive interviews at three AIAN communities to assess the item quality of a 131-item survey item that measures AIAN knowledge and attitudes on genetics and biological specimens. A cognitive interview process was used to assess cultural consonance, thought processes used when considering survey instructions, items and responses, and language preference of survey items in the development of a survey to assess public knowledge and attitudes on genetics. Content analysis was used to analyze interview data. Survey instructions, items and scales generated no cognitive difficulties. The participants noted being unfamiliar with terminology used to describe genetic and biological specimens. In several cases, the participants' written response in the survey and verbal response in the interview did not align. A resultant 52-item survey for use in AIAN communities was finalized. Cognitive interviewing is resource-intensive; however, ignoring community engagement during survey development results in inappropriate interpretations about culturally diverse populations such as AIAN peoples.

Introduction: Alaska Native and American Indian (ANAI) people have a smoking prevalence of 23%. Nicotine metabolite ratio (NMR) and genetic testing may enable tailored selection of tobacco cessation medication., Aims and Methods: The purpose of this study was to evaluate the relative contributions of NMR, cessation medication, demographics, and tobacco use history to cessation. Participants were recruited into an observational cohort study consisting of a baseline visit prior to their quit date and 6-week follow-up. Demographic and tobacco use surveys and blood, urine, and breath samples were collected at each visit. Electronic health records were queried for cessation medications. NMR was categorized into slow or normal nicotine metabolism phenotypes (<0.31 and ≥ 0.31, respectively). The main outcome was cessation at 6 weeks. Analyses consisted of descriptive statistics, medication and phenotype concordance, and estimates of relative risk (RR) of quitting., Results: We enrolled 151 ANAI adults who smoked cigarettes daily. Two-thirds had normal nicotine metabolism phenotype. Retrospective medication and phenotype concordance was 39%. The overall quit rate was 25%. No demographic factors or tobacco use history were associated with quit success. Varenicline and bupropion increased the likelihood of quitting (RR = 2.93 [1.42, 6.03] and RR = 2.52 [1.12, 5.64], respectively) compared to nicotine replacement therapy. Non-optimal medication and phenotype concordance decreased likelihood of quit success (RR = 0.44 [0.22, 0.91]) compared to optimal concordance., Conclusions: This exploratory study found associations between quit success and tobacco cessation medication as well as medication and phenotype concordance. Additional research is needed to assess use of NMR for treatment selection among ANAI people., Implications: These results broadly support additional community-engaged research to improve medication and phenotype concordance in tribal health settings. Such future research on implementing meditcation and phenotype concordance holds promise to improve expectations, quit success, and health outcomes amongst individuals attempting to quit smoking., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Newborn screening in Alaska includes screening for carnitine palmitoyltransferase 1A (CPT1A) deficiency. The CPT1A Arctic variant is a variant highly prevalent among Indigenous peoples in the Arctic. In this study, we sought to elicit Alaska Native (AN) community member and AN-serving healthcare providers' knowledge and perspectives on the CPT1A Arctic variant. Focus groups with community members and healthcare providers were held in two regions of Alaska between October 2018 and January 2019. Thematic analysis was used to identify recurring constructs. Knowledge and understanding about the CPT1A Arctic variant and its health impact varied, and participants were interested in learning more about it. Additional education for healthcare professionals was recommended to improve providers' ability to communicate with family caregivers about the Arctic variant. Engagement with AN community members identified opportunities to improve educational outreach via multiple modalities for providers and caregivers on the Arctic variant, which could help to increase culturally relevant guidance and avoid stigmatization, undue worry, and unnecessary intervention. Education and guidance on the care of infants and children homozygous for the CPT1A Arctic variant could improve care and reduce negative psychosocial effects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alaska Native communities are working to prevent cancer through increased cancer screening and early detection. We examined the prevalence of self-reported colorectal (CRC), cervical, and breast cancer screening among Alaska Native participants in the southcentral Alaska Education and Research toward Health (EARTH) study at baseline (2004-2006) and ten-year follow-up (2015-2017); participant characteristics associated with screening; and changes in screening prevalence over time. A total of 385 participants completed questionnaires at follow-up; 72% were women. Of those eligible for CRC screening, 53% of follow-up participants reported a CRC screening test within the past 5 years, significantly less than at baseline (70%) ( p = 0.02). There was also a significant decline in cervical cancer screening between baseline and follow-up: 73% of women at follow-up vs. 90% at baseline reported screening within the past three years ( p < 0.01). There was no significant difference in reported breast cancer screening between baseline (78%) and follow-up (77%). Colorectal and cervical cancer screening prevalence in an urban, southcentral Alaska Native cohort declined over 10 years of follow-up. Increased cancer screening and prevention are needed to decrease Alaska Native cancer-related morbidity and mortality.

Introduction: Precision medicine research investigates the differences in individuals' genetics, environment, and lifestyle to tailor health prevention and treatment options as part of an emerging model of health care delivery. Advancing precision medicine research will require effective communication across a wide range of scientific and health care disciplines and with research participants who represent diverse segments of the population., Methods: A multidisciplinary group convened over the course of a year and developed precision medicine research case examples to facilitate precision medicine research discussions with communities., Results: A shared definition of precision medicine research as well as six case examples of precision medicine research involving genetic risk, pharmacogenetics, epigenetics, the microbiome, mobile health, and electronic health records were developed., Discussion/conclusion: The precision medicine research definition and case examples can be used as planning tools to establish a shared understanding of the scope of precision medicine research across multidisciplinary teams and with the diverse communities in which precision medicine research will take place. This shared understanding is vital for successful and equitable progress in precision medicine., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The American Indian/Alaska Native (AI/AN) suicide rate in Alaska is twice the state rate and four times the U.S. rate. Healthcare systems need innovative methods of suicide risk detection. The Mental Health Research Network (MHRN) developed suicide risk prediction algorithms in a general U.S., Methods: We applied MHRN predictors and regression coefficients to electronic health records of AI/AN patients aged ≥13 years with behavioral health diagnoses and primary care visits between October 1, 2016, and March 30, 2018. Logistic regression assessed model accuracy for predicting and stratifying risk for suicide attempt within 90 days after a visit. We compared expected to observed risk and assessed model performance characteristics., Results: 10,864 patients made 47,413 primary care visits. Suicide attempt occurred after 589 (1.2%) visits. Visits in the top 5% of predicted risk accounted for 40% of actual attempts. Among visits in the top 0.5% of predicted risk, 25.1% were followed by suicide attempt. The best fitting model had an AUC of 0.826 (95% CI: 0.809-0.843)., Conclusions: The MHRN model accurately predicted suicide attempts among AI/AN patients. Future work should develop clinical and operational guidance for effective implementation of the model with this population., (© 2022 The American Association of Suicidology.)

Introduction: Data on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with current use., Aims and Methods: EARTH Study urban south central ANAI participants (N = 376; 73% women) provided questionnaire data on smoking at baseline and 10-year follow-up. Multivariable-adjusted logistic regression assessed whether gender, cultural factors (Tribal identity, language spoken in the home), depressive symptoms (PHQ-9), baseline smoking status, and baseline cigarettes per day (CPD) were associated with current smoking at follow-up., Results: Current smoking was 27% and 23% at baseline and follow-up, respectively. Of baseline smokers, 60% reported smoking at follow-up (77% men, 52% women). From multivariable-adjusted analyses, the odds of current smoking at follow-up were lower among women than men, those who never or formerly smoked versus currently smoked at baseline, and smoking <10 CPD compared with ≥10 CPD at baseline. PHQ-9 score or cultural variables were not associated with smoking at follow-up. Smoking fewer baseline CPD was associated with former smoking status (ie, quitting) at follow-up among women, but not men., Conclusions: Our project is among the first to longitudinally explore smoking within an ANAI cohort. While we observed persistent smoking during a 10-year period, there were important differences by gender and CPD in quitting. These differences may be important to enhance the reach and efficacy of cessation interventions for ANAI people., Implications: This study contributes novel longitudinal information on cigarette smoking prevalence during a 10-year period among Alaska Native and American Indian (ANAI) people. Prior data on smoking prevalence among ANAI people are limited to cross-sectional studies or specific subpopulations. Our project is among the first to longitudinally explore smoking prevalence within an ANAI cohort. We observed persistent smoking during a 10-year period. The study also contributes information on differences by gender and cigarettes smoked per day in quitting. These findings have implications for enhancing the reach and efficacy of cessation interventions for ANAI people., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Genetic datasets lack diversity and include very few data from Indigenous populations. Research models based on equitable partnership have the potential to increase Indigenous participation and have led to successful collaborations. We report here on a meeting of participants in four Indigenous community-university partnerships pursuing research on precision medicine. The goal of the meeting was to define values and practices that strengthen opportunities for genetic research. The group accorded the highest priority to developing trusting relationships, ensuring respect for Indigenous community authority, and pursuing research that has the potential to lead to community benefit. Supporting priorities included incorporation of Indigenous expertise in research planning, transparent communication, and development of community capacity, including capacity to participate in formulating research questions, informing research methodology, and leading research projects. Participants also noted the importance of attention to social determinants of health so that genetic contributors to health are evaluated in the appropriate context.

Participant retention in longitudinal health research is necessary for generalizable results. Understanding factors that correlate with increased retention could improve retention in future studies. Here, we describe how participant and study process measures are associated with retention in a longitudinal tobacco cessation research study performed in Anchorage, Alaska. Specifically, we conducted a secondary analysis exploring retention among 151 Alaska Native and American Indian (ANAI) people and described our study processes using study retention categories from a recent meta-analysis. We found that our study processes influence retention among ANAI urban residents more than measures collected about the participant. For study process measures, calls where a participant answered and calls participants placed to the study team were associated with higher retention. Calls where the participant did not answer were associated with lower retention. For participant measures, only lower annual income was associated with lower retention at 6 weeks. Promoting communication from participants to the study team could improve retention, and alternative communication methods could be used after unsuccessful calls. Finally, categorizing our study retention strategies demonstrated that additional barrier-reduction strategies might be warranted.

Objective: To identify risk factors for postpartum hemorrhage in a population of Alaska Native women., Methods: A case-control study of 384 women (128 cases, 256 controls) delivering between August 1, 2018, and July 31, 2019, was conducted at a Level III maternal referral center for Alaska Native women in Alaska. Risk factors were assessed via retrospective chart review, and bivariate and conditional regression analyses were conducted to determine odds ratios (ORs) between women with and without postpartum hemorrhage., Results: Body mass index ≥40 (OR 2.6, 95% confidence interval [CI] 1.4-4.5), antepartum bleeding (OR 6.3, 95% CI 1.2-31.6), previous postpartum hemorrhage (OR 5, 95% CI 2.6-9.8), suspected macrosomia (OR 2.7, 95% CI 1.4-5.3), macrosomia with birthweight ≥4000 g (OR 3.1, 95% CI 1.8-5.3), pre-eclampsia with magnesium sulfate (OR 4.0, 95% CI 2.0-8.0), length of third stage of labor >20 min (OR 2.2, 95% CI 1.1-4.4), oxytocin use >12 h (OR 5.4, 95% CI 2.0-14.6), residence in a rural community (OR 2.2, 95% CI 1.4-3.6), and vitamin D supplementation (OR 1.7, 95% CI 1.1-2.6) were associated with greater risk of postpartum hemorrhage., Conclusion: Analysis of clinical and geographic risk factors for postpartum hemorrhage in Alaska Native women identified important targets for prevention., (© 2021 International Federation of Gynecology and Obstetrics.)

Prevalence of smoking is higher in Alaska Native and American Indian (ANAI) populations living in Alaska than the general US population. Genetic factors contribute to smoking and cessation rates. The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. ANAI (N = 151) people trying to quit smoking were recruited. DNA samples were genotyped for CYP2A6 variants *1X2A, *1B, *2, *4, *9, *10, *12, and *35. Multiple nicotine metabolites were measured in plasma and urine samples, including cotinine and 3'-hydroxycotinine used to determine CYP2A6 activity (e.g., nicotine metabolite ratio [NMR]). We calculated summary statistics for all of the genotypes and metabolites and assigned CYP2A6 activity scores based on known information. We studied the association of CYP2A6 variants with the NMR and smoking histories. The overall frequency of the CYP2A6*1B gain of function allele was high in the ANAI versus non-ANAI populations in other studies. Both *4 null and *9 decrease of function alleles had frequencies similar to previous studies of ANAI populations. In a multivariate analysis, the genotype-inferred CYP2A6 activity score was associated with both plasma and urine NMR (p value = 8.56E-08 and 4.08E-13, respectively). Plasma NMR was also associated with duration of smoking (p value < 0.01) but not urinary total nicotine equivalents uncorrected for creatinine (TNE9 uc ) or biological sex. Urine NMR was significantly associated (p value < 0.01) with TNE9 uc . Variation in NMR in this ANAI population is explained in part by CYP2A6 genetic variation., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The history of research in American Indian/Alaska Native (AI/AN) communities has been marked by unethical practices, resulting in mistrust and reluctance to participate in research. Harms are not limited to individual persons-tribal communities experience harmful misrepresentation and generalizations disrespectful of AI/AN groups' heritage, cultures, and beliefs. The Belmont Report's research ethics principles are applied primarily to protect individual research participants. The principles of sovereignty and solidarity are argued to be important concepts in extending Belmont's research protections to tribal communities. Sovereignty, an expression of respect for autonomy at a group level, is the basis for tribal self-determination. The principle of solidarity provides an ethical underpinning for tribes' obligations to protect community interests and culture. Extension of Belmont through these principles should serve to minimize harms to AI/AN groups in research.

Background: This paper describes the design, implementation, and process outcomes from three public deliberations held in three tribal communities. Although increasingly used around the globe to address collective challenges, our study is among the first to adapt public deliberation for use with exclusively Indigenous populations. In question was how to design deliberations for tribal communities and whether this adapted model would achieve key deliberative goals and be well received., Methods: We adapted democratic deliberation, an approach to stakeholder engagement, for use with three tribal communities to respect tribal values and customs. Public deliberation convenes people from diverse backgrounds in reasoned reflection and dialogue in search of collective solutions. The deliberation planning process and design were informed by frameworks of enclave deliberation and community-based participatory research, which share key egalitarian values. The deliberations were collaboratively designed with tribal leadership and extensive partner input and involvement in the deliberations. Each deliberation posed different, locally relevant questions about genomic research, but used the same deliberation structure and measures to gauge the quality and experience of deliberation., Results: A total of 52 individuals participated in the deliberations across all three sites. Deliberants were balanced in gender, spanned decades in age, and were diverse in educational attainment and exposure to health research. Overall, the deliberations were positively evaluated. Participant perceptions and external observer datasets depict three deliberations that offered intensive conversation experiences in which participants learned from one another, reported feeling respected and connected to one another, and endorsed this intensive form of engagement., Conclusion: The adapted deliberations achieved key deliberative goals and were generally well received. Limitations of the study are described.

Background: Precision medicine (PM) research and clinical application is moving forward at a rapid pace. To ensure ethical inclusion of all populations in PM, in-depth understanding of diverse communities' views of PM research and PM implementation is necessary., Methods: Semi-structured interviews were conducted to explore perspectives on PM in a tribally managed healthcare organization. Thematic analysis was used to analyze data from 46 interviews., Results: Participants described gains in diagnostic efficiency, risk identification for preventable disease, and the advancement of population-specific biomedical research as key benefits of PM. Concerns expressed related to privacy risks associated with data-sharing, overpromising on PM, and managing patient expectations related to PM. Stakeholders encouraged PM implementation to be preceded by health education activities that leverage a range of communication strategies., Conclusion: Perspectives described in this study may aid in and should be considered prior to implementation of PM in this and other healthcare systems, especially those serving diverse populations.

Genomic research raises unique ethical concerns among Alaska Native and American Indian (AN/AI) people and their communities. The Center for the Ethics of Indigenous Genomic Research (CEIGR) was created to foster research that takes these concerns into account while considering the sovereign status of AN/AI tribal nations. Relationships developed within CEIGR have allowed for effective, collaborative research among individuals who come from diverse cultures, political and historical backgrounds, and academic disciplines, and who work for organizations with varying resources, capacities, and expectations. The CEIGR framework may inform other groups seeking to conduct social science research related to genomic research with tribal people and their communities.

Background: Precision medicine seeks to better tailor medical care to the needs of individual patients, but there are challenges involved in communicating to patients, health care providers, and health system leaders about this novel and complex approach to research and clinical care. These challenges may be exacerbated for Alaska Native and American Indian (ANAI) people, whose experiences of unethical research practices have left some ANAI communities hesitant to engage in research that involves extensive data-sharing and diminished control over the terms of data management and who may have distinct, culturally-informed communication needs and preferences. There is need for communication research to support Tribal health organizations and ANAI people as they consider implementation of and participation in precision medicine. To address that need, this study characterizes the informational needs and communication preferences of patients, providers, and leaders at an Alaska Native Tribal health organization., Methods: We conducted 46 individual, semi-structured interviews to explore perspectives on precision medicine and related communication needs among patients, providers, and leaders of a Tribal health organization. Analysis involved team-based coding to identify a priori and emergent themes, followed by identification and recoding of content relevant to precision medicine informational needs and communication preferences., Results: Patients, providers, and leaders were described as both sources and recipients of information about precision medicine. Information deemed essential for making decisions about whether to participate in or implement a precision medicine program included information about the clinical and research applications of precision medicine, benefits and risks, health system costs and impacts, and data management practices. Preferred communication channels included digital and non-digital informational materials, as well as in-person learning opportunities for individuals and groups. Participants also describe contextual factors and barriers that influenced the acceptability and effectiveness of approaches to health communication., Conclusion: Results can inform approaches to communicating information about precision medicine to stakeholders within Tribal and other health care systems considering implementation of precision medicine in clinical or research contexts., Competing Interests: Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Aims: This study estimates incidence of diabetes (DM) and pre-DM relative to DM risk factors among relatively healthy Alaska Native and American Indian (henceforth AN) adults living in urban south central Alaska., Methods: Baseline (2004-2006) and follow-up (2014-2017) surveys, blood samples, and medical chart review data were collected from AN adults living in south central Alaska. We analyzed associations between prevalent risk factors and incident DM and pre-DM using Cox proportional hazards and used multivariable models to identify independent predictors for both DM and pre-DM., Results: Among 379 participants with follow-up data, overall DM incidence was 16.5/1,000 PY; overall pre-DM incidence was 77.6/1,000 PY, with marked differences between men and women. Prevalent cardiometabolic risk factors also varied with greater amounts of overweight in men and greater amounts of obesity in women. Controlling for age and sex, obesity, abdominal adiposity, pre-DM, and metabolic syndrome independently increased DM risk., Conclusion: Health care providers of AN populations must seize the opportunity to screen, refer, and treat individuals with pre-DM and other modifiable DM risk factors prior to DM diagnosis if we are to alter the epidemiologic course of disease progression in this urban AN population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation., Methods: Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations)., Results: Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup., Conclusions: Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations., Implications: Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

As genetic testing technology advances, genetic testing will move into standard practice in the primary care setting. Genetic research, testing, and return of results are complex topics that require input from Alaska Native and American Indian (ANAI) communities as policies are developed for implementation. This study employed a day and half long public deliberation with ANAI primary care patients to elicit value-laden views of genetic research, testing, and return of results. Participants emphasized the need for a balance between the potential for genetics research, testing, and return of results to empower individuals and improve health with the potential to expose individuals and communities to privacy breaches, discrimination, and emotional harms. Public deliberation was well received by this group of participants and elicited rich discussion on the complex topic of genetic research, testing, and return of results., Competing Interests: The authors have declared that no competing interests exist.

Persistent, unresolved issues stemming from a legacy of scientific exploitation and bio-colonialism have kept many tribal nations from participating in genomic research. The Center for the Ethics of Indigenous Genomic Research (CEIGR) aims to model meaningful community engagement that moves toward more inclusive and equitable research practices related to genomics. This article reflects on key successes and challenges behind CEIGR's efforts to shape Ethical, Legal and Social Implications (ELSI) research in ways that are informed by Indigenous perspectives, to locate community partnerships at the center of genomics research, and to conduct normative and empirical research with Indigenous communities that is grounded in the concepts of reciprocity, transparency and cultural competency. The structure of CEIGR represents an important shift away from a traditional model centered on a university-based principal investigators toward a partner-centered research approach that emphasizes equity and community control by distributing power and decision-making across all CEIGR partner sites. We discuss three features of CEIGR that have contributed to this shift towards an equitable, community-driven partnership: 1) balancing local priorities with collective goals; 2) distributing power in ways that promote equitable partnerships; and 3) capacity building and co-learning across partner sites. The discussion of these three areas in this article speaks to a particular strength of our Center: the interdependence among partners and collective willingness to maintain a plasticity of leadership that creates space for all of our partners to lead, support, exchange and strengthen ELSI research., Competing Interests: Competing Interests The authors have no competing interests to declare.

This study explored the lived experiences of suicidality and help-seeking for suicide prevention among Alaska Native and American Indian (AN/AI) people in a tribal health system. An interpretive phenomenological approach was used to analyze semi-structured, in-depth interviews with 15 individuals (ages 15-56) with self-reported histories of suicide ideation and/or attempt. Several factors were found to be central to acquiring resilience to suicide risk among AN/AI people across a wide age range: meaningful and consistent social connection, awareness about how one's suicide would negatively effect loved ones, and knowledge and utilization of available health services. Findings highlight the mutable nature of suicide risk and resilience, as well as the importance of interpersonal factors in suicidality.

Background: Multiple factors, including experiences with unethical research practices, have made some Indigenous groups in the United States and Canada reticent to participate in potentially beneficial health-related research. Yet, Indigenous peoples have also expressed a willingness to participate in research when certain conditions related to the components of data management-including data collection, analysis, security and storage, sharing, dissemination, and withdrawal-are met. A scoping review was conducted to better understand the terms of data management employed in health-related research involving Indigenous communities in the United States and Canada. Methods: PubMed, Embase, PsychINFO, and Web of Science were searched using terms related to the populations and topics of interest. Results were screened and articles deemed eligible for inclusion were extracted for content on data management, community engagement, and community-level research governance. Results: The search strategy returned 734 articles. 31 total articles were extracted, of which nine contained in-depth information on data management and underwent detailed extraction. All nine articles reported the development and implementation of data management tools, including research ethics codes, data-sharing agreements, and biobank access policies. These articles reported that communities were involved in activities and decisions related to data collection (n=7), data analysis (n=5), data-sharing (n=9), dissemination (n=7), withdrawal (n=4), and development of data management tools (n=9). The articles also reported that communities had full or shared ownership of (n=5), control over (n=9), access to (n=1), and possession of data (n=5). All nine articles discussed the role of community engagement in research and community-level research governance as means for aligning the terms of data management with the values, needs, and interests of communities. Conclusions: There is need for more research and improved reporting on data management in health-related research involving Indigenous peoples in the United States and Canada. Findings from this review can provide guidance for the identification of data management terms and practices that may be acceptable to Indigenous communities considering participation in health-related research., (Copyright © 2019 Woodbury, Beans, Hiratsuka and Burke.)

Background: Alaska Native (AN) traditional foods and associated harvesting activities are beneficial to human health., Objective: This study assessed longitudinal self-reported traditional food use and harvesting activities among Alaska Native and American Indian (AN/AI) participants in the Alaska Education and Research Towards Health (EARTH) study., Methods: In 2004-2006, southcentral Alaska EARTH study participants ( n  = 1320) completed diet and activity questionnaires which were repeated in 2015-2017; results were compared between participants who completed both questionnaires ( n  = 388)., Results: In the follow-up questionnaire, >93% of participants reported eating ≥1 traditional food in the past year. The top 3 traditional foods were fish (75%), moose (42%), and shellfish (41%). Women were more likely than men to consume traditional foods, especially fish, gathered berries, shellfish, and seal oil ( P  < 0.05). Participants aged ≥60 y in the original cohort were significantly more likely to consume fish and shellfish at follow-up, whereas those aged 40-59 y were the most likely of the 3 age groups to consume seal oil ( P  < 0.05). Between the original cohort and follow-up, there was a significant decline in the mean number of traditional foods eaten from 6.3 to 5.5, as well as reduced consumption of multiple traditional foods ( P  < 0.001). Over 59% of participants reported ≥1 traditional harvesting activity in the past year; this proportion did not significantly change between baseline and follow-up. Picking berries/greens (44%), cutting/smoking fish or meat (33%), and fishing (30%) were the most common activities. Participation in traditional harvesting activities was greater among women than men ( P  < 0.05), but did not differ by age., Conclusions: Longitudinal follow-up demonstrated that AN/AI people maintained participation in traditional harvesting activities, but the variety of traditional foods declined significantly among both men and women. Promotion of traditional foods and harvesting activities that serve as protective factors against chronic diseases may benefit this population., (Copyright © The Author(s) 2019.)

Longitudinal data are needed to investigate chronic disease causation and improve prevention efforts for Alaska Native and American Indian (ANAI) people. This paper describes the methods used to conduct follow-up data collection of a longitudinal cohort that enrolled ANAI adults between 2004 and 2006 in south central Alaska. The follow-up study re-examined ANAI participants in a large, urban centre in south central Alaska between 2015 and 2017. Computerized surveys were used to collect self-reported health, lifestyle, physical activity, and diet data. Clinical measurements included blood pressure, fasting blood glucose and lipid panel, urine albumin/creatinine, height, weight, and waist and hip circumference. Participants were provided individual results at the conclusion of their visit. A total of 1320 south central Alaska study participants completed the baseline visit. Study staff attempted to contact all living cohort members for inclusion in the follow-up study. More than 11,000 attempted contacts were made. Of the 637 available for participation, 388 completed the follow-up visit. The proportion of women increased from baseline to follow-up examinations (67 vs. 72%, p < 0.01). Self-reported health status of being married or living as married (46% vs. 39%, p < 0.01), and those reporting being employed or self-employed (55% vs. 47%, p < 0.01) were higher at follow-up when compared to baseline. Almost all participants at follow-up (97%) agreed to long-term storage of biological specimens for future study. Despite demographic differences between the follow-up and baseline cohorts, longitudinal data collected will provide novel insight on chronic disease development and prevention for ANAI people as well as other populations.

Precision medicine initiatives, such as Cancer Breakthrough 2020, promise to improve cancer outcomes by tailoring treatment to an individual's genes, environment, and lifestyle. This promise will fall short unless researchers successfully engage diverse communities, including those with histories of medical and research abuse. We examined a rural Alaska Native community's viewpoints about biospecimen collection and storage; interest and recall in reporting family health history; and interest and engagement in biospecimen collection for conducting a genetic test for cancer. In 2014, four focus groups were held with 28 adult Alaska Native rural community members. Thematic analysis was performed after establishing a coding scheme by team consensus. Study participants shared interest in engaging in genetic cancer research and suggested ways to improve community engagement in research. These included transparency and continuous communication with researchers at all stages of the research, clear communication about the intent of the research, and that research and results take into consideration the community's needs. These suggestions may be beneficial for future efforts to expand precision medicine research in Alaska Native communities and similar, diverse populations.

Experiences with unethical research practices have caused some American Indian and Alaska Native (AIAN) individuals, organizations, and tribes to mistrust health research. To build trust and repair relationships, current research with AIAN peoples often involves participatory research (PR) approaches. This article assesses community-level protections described in the scientific literature on PR involving AIAN communities. A scoping review search in PubMed and PsychInfo for articles published between January 2000 and June 2017 yielded an AIAN PR article dataset. Of 178 articles, a subset of 23 articles that described aspects of community protections were analyzed for descriptions of community-level protection practices. We identified the presence or absence of a description of four community protection measures in each article: a tribal research department, the development of community-level mechanisms for research regulation if not present, community collaboration throughout the research process, and project employment of a community member. The development of community-level mechanisms for research regulation was described in 39% of the articles. Ninety-one percent of these articles described community collaboration during the research process. Seventeen percent included descriptions of all four community-level protection measures. The extent and consistency to which community-level protections are described is variable; the current literature lacks reporting on community-level protection practices specific to tribal communities., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Despite evidence that pharmacogenetics can improve tamoxifen pharmacotherapy, there are few studies with American Indian and Alaska Native (AIAN) people. We examined variation in cytochrome P450 (CYP) genes (CYP2D6, CYP3A4, CYP3A5, and CYP2C9) and tamoxifen biotransformation in AIAN patients with breast cancer (n = 42) from the Southcentral Foundation in Alaska and the Confederated Salish and Kootenai Tribes in Montana. We tested for associations between CYP diplotypes and plasma concentrations of tamoxifen and metabolites. Only the CYP2D6 variation was significantly associated with concentrations of endoxifen (P = 0.0008) and 4-hydroxytamoxifen (P = 0.0074), tamoxifen's principal active metabolites, as well as key metabolic ratios. The CYP2D6 was also the most significant predictor of active metabolites and metabolic ratios in a multivariate regression model, including all four genes as predictors, with minor roles for other CYP genes. In AIAN populations, CYP2D6 is the largest contributor to tamoxifen bioactivation, illustrating the importance of validating pharmacogenetic testing for therapy optimization in an understudied population., (© 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Alaska Native and American Indian (AN/AI) people experience a disproportionate burden of health disparities in the United States. Including AN/AI people in pharmacogenetic research offers an avenue to address these health disparities, however the dissemination of pharmacogenetic research results in the community context can be a challenging task. In this paper, we describe a case-study that explores the preferences of AN/AI community members regarding pharmacogenetic research results dissemination. Results were presented as a PowerPoint presentation at the 2016 Alaska Native Health Research Forum (Forum). An audience response system and discussion groups were used to gather feedback from participants. Descriptive statistics were used to assess attendee understanding of the presentation content. Thematic analysis was used to analyze discussion group data. Forum attendees needed time to work through the concept of pharmacogenetics and looked for ways pharmacogenetics could apply to their daily life. Attendees found pharmacogenetics interesting, but wanted a simple description of pharmacogenetics. Community members were optimistic about the potential benefit pharmacogenetic medicine could have in the delivery of health care and expressed excitement this research was taking place. Researchers were urged to communicate throughout the study, not just end research results, to the community. Furthermore, attendees insisted their providers stay informed of research results that may have an impact on health care delivery. Conversational forms of dissemination are recommended when disseminating pharmacogenetic research results at the community level.

In May 2016, Southcentral Foundation (SCF), a regional tribal health corporation based in Anchorage, Alaska convened a half-day health research forum for Alaska Native and American Indian community members to obtain feedback on communication of research findings. Thirty one individuals attended the Forum and 22 completed a pre and post survey. Respondents found the Forum to be a useful method to learn about research projects and their willingness to participate in health research reportedly increased because of the event. Forum attendees also endorsed use of direct mail, electronic mail, and messages via an electronic health record patient portal as communication methods for health researchers to inform potential participants about research studies occurring at SCF and for return of individual and community level results.

Southcentral Foundation, a tribal health organization serving Alaska Native and American Indian (AN/AI) people in southcentral Alaska, convened the Alaska Native Health Research Forum (Forum) for AN/AI people in May 2016. The purpose of the Forum was to obtain AN/AI community member feedback about sharing health research results. This article describes the funding mechanism that provided resources for the Forum and other factors that were considered when designing the Forum. This is followed by a description of how attendees were invited, the audience response system, and process used to collect quantitative data on participants and qualitative feedback from small group discussions with Forum attendees. Finally, we describe the quantitative and qualitative data analysis processes used to evaluate responses.

Alaska Native (AN) and American Indian (AI) people are underrepresented in health research, yet many decline to participate in studies due to past researcher misconduct. Southcentral Foundation (SCF), an Alaska Native-owned and operated health care organization, is transforming the relationship between researchers and the tribal community by making trust and accountability required features of health research in AN/AI communities. In 1998, SCF assumed ownership from the federal government of health services for AN/AI people in south central Alaska and transformed the health system into a relationship-based model of care. This change reimagines how researchers interact with tribal communities and established community oversight of all health research conducted with AN/AI people in the region. We describe the SCF research review process, which requires tribal approval of the research concept, full proposal, and dissemination products, as well as local institutional review board approval, and a researcher-signed contract. This review evaluates research through the lens of tribal principles, practices, and priorities. The SCF example provides a framework for other tribes and organizations seeking to reshape the future of health research in AN/AI communities., Competing Interests: The authors declare no conflict of interest.

Aim: Describe patients,' providers' and healthcare system leaders' perceptions of pharmacogenetic research to guide tobacco cessation treatment in an American Indian/Alaska Native primary care setting., Materials & Methods: This qualitative study used semistructured interviews with 20 American Indian/Alaska Native current or former tobacco users, 12 healthcare providers and nine healthcare system leaders., Results: Participants supported pharmacogenetic research to guide tobacco cessation treatment provided that a community-based participatory research approach be employed, research closely coordinate with existing tobacco cessation services and access to pharmacogenetic test results be restricted to providers involved in tobacco cessation., Conclusion: Despite a history of mistrust toward genetic research in tribal communities, participants expressed willingness to support pharmacogenetic research to guide tobacco cessation treatment.

Background: American Indian (AI) and Alaska Native (AN) communities confront some of the highest rates of tobacco use and its sequelae., Methods: This formative research project sought to identify the perspectives of 41 stakeholders (community members receiving care within the healthcare system, primary care providers, and tribal healthcare system leaders) surrounding the use of pharmacogenetics toward tobacco cessation treatment in the setting of an AI/AN owned and operated health system in south central Alaska., Results: Interviews were held with 20 adult AI/AN current and former tobacco users, 12 healthcare providers, and 9 tribal leaders. An emergent theme from data analysis was that current tobacco screening and cessation efforts lack information on electronic cigarette (e-cigarette) use. Perceptions of the use of e-cigarettes role in tobacco cessation varied., Conclusion: Preventive screening for tobacco use and clinical cessation counseling should address e-cigarette use. Healthcare provider tobacco cessation messaging should similarly address e-cigarettes.