Identification of Sociodemographic, Clinical, and Genetic Factors to Aid Alaska Native and American Indian People to Successfully Quit Smoking.

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.

Measuring Attitudes About Alcohol Misuse and Dependence Among Alaska Native People Within a Tribal Health Care System.

OBJECTIVES: Attitudes about alcohol misuse and dependence influence alcohol use and help-seeking behavior. Alaska Native and American Indian (AN/AI) people have higher rates of alcohol-related morbidity and mortality but engage in treatment at lower rates than the general population. No validated instruments exist to assess attitudes of AN/AI people about alcohol misuse and dependence to inform treatment and prevention efforts. This study aimed to develop an instrument to assess public attitudes among AN/AI people of alcohol misuse and dependence. METHODS: This multiphase, mixed-methods study was conducted at Southcentral Foundation, a tribally owned health system serving 65,000 AN/AI people in Alaska. We conducted focus groups and interviews with health system users, providers, and leaders to adapt the Public Attitudes About Addiction Survey. The adapted instrument was piloted with 200 people. Cognitive interviews and exploratory and confirmatory factor analyses were used to refine the instrument, which were then administered to 777 AN/AI people. RESULTS: Initial exploratory factor analysis identified 5 factors, including 3 from the original Public Attitudes About Addiction Survey (moral, disease, nature), a combined psychology and sociology factor (psychosocial), and a new factor (environment). A final 4-factor model (psychosocial, moral, disease, nature) with 14 items had good fit with root mean square error of approximation (0.035; comparative fit index = 0.977; Tucker-Lewis index = 0.970; standardized root mean residual = 0.040) and loadings ranging from 0.41 to 0.80. CONCLUSIONS: This study developed the first instrument to assess AN/AI attitudes about alcohol misuse and dependence. This instrument has potential to inform alcohol-related treatment in AN/AI communities. Future research is warranted to adequately measure place-based contributors salient to AN/AI people.

Ensuring equity: Pharmacogenetic implementation in rural and tribal communities.

Implementation strategies for pharmacogenetic testing have been largely limited to major academic medical centers and large health systems, threatening to exacerbate healthcare disparities for rural and tribal populations. There exists a need in Montana (United States)-a state where two-thirds of the population live in rural areas and with a large proportion of tribal residents-to develop novel strategies to make pharmacogenetic testing more broadly available. We established partnerships between University of Montana (UM) and three early adopter sites providing patient-centered care to historically neglected populations. We conducted 45 semi-structured interviews with key stakeholders at each site and solicited participant feedback on the utility of a centralized pharmacogenetic service at UM offering consultations to patients and providers statewide via telehealth. For settings serving rural patients-tribal and non-tribal-participants described healthcare facilities without adequate infrastructure, personnel, and funding to implement pharmacogenetic services. Participants serving tribal communities stressed the need for ethical practices for collecting biospecimens and returning genetic results to patients, largely due to historical and contemporary traumas experienced by tribal populations with regard to genetic research. Participants expressed that pharmacogenetic testing could benefit patients by achieving therapeutic benefit sooner, reducing the risk of side effects, and improving adherence outcomes for patients with limited access to follow-up services in remote areas. Others expressed concern that financial barriers to pharmacogenetic testing for patients of lower socioeconomic status would further exacerbate inequities in care. Participants valued the role of telehealth to deliver pharmacogenetic consults from a centralized service at UM, describing the ability to connect providers and patients to resources and expertise as imperative to driving successful pharmacogenetic implementation. Our results support strategies to improve access to pharmacogenetic testing for neglected patient populations and create opportunities to reduce existing healthcare inequities. By exploring critical challenges for pharmacogenetic implementation focused on serving underserved communities, this work can help guide equitable frameworks to serve as a model for other resource-limited settings looking to initiate pharmacogenetic testing.

Communicating Precision Medicine Research: Multidisciplinary Teams and Diverse Communities.

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.

Perceived Social Influences on Women's Decisions to use Medications not Studied in Pregnancy. A Qualitative Ethical Analysis of Preexposure Prophylaxis Implementation Research in Kenya.

Implementation research ethics can be particularly challenging when pregnant women have been excluded from earlier clinical stages of research given greater uncertainty about safety and efficacy in pregnancy. The evaluation of human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) during pregnancy offered an opportunity to understand important ethical considerations and social influences shaping women's decisions to participate in the evaluation of PrEP and investigational drugs during pregnancy. We conducted interviews with women (n = 51), focus groups with male partners (five focus group discussions [FGDs]), interviews with health providers (n = 45), four FGDs with pregnant/postpartum adolescents and four FGDs with young women. Data were analyzed using thematic content analysis, including ethical aspects of the data. Our study reveals that women navigate a complex network of social influences, expectations, support, and gender roles, not only with male partners, but also with clinicians, family, and friends when making decisions about PrEP or other drugs that lack complete safety data during pregnancy.

Alaska Native genomic research: perspectives from Alaska Native leaders, federal staff, and biomedical researchers.

Meaningful engagement of Alaska Native (AN) tribes and tribal health organizations is essential in the conduct of socially responsible and ethical research. As genomics becomes increasingly important to advancements in medicine, there is a risk that populations not meaningfully included in genomic research will not benefit from the outcomes of that research. AN people have historically been underrepresented in biomedical research; AN underrepresentation in genomics research is compounded by mistrust based on past abuses, concerns about privacy and data ownership, and cultural considerations specific to this type of research. Working together, the National Human Genome Research Institute and two Alaska Native health organizations, Southcentral Foundation and the Alaska Native Health Board, cosponsored a workshop in July 2018 to engage key stakeholders in discussion, strengthen relationships, and facilitate partnership and consideration of participation of AN people in community-driven biomedical and genomic research. AN priorities related to translation of genomics research to health and health care, return of genomic results, design of research studies, and data sharing were discussed. This report summarizes the perspectives that emerged from the dialogue and offers considerations for effective and socially responsible genomic research partnerships with AN communities.

Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study.

BACKGROUND: Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES. PURPOSE: To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT). METHODS: The primary outcome was clinical sensitivity for the diagnosis of inherited CRCP; secondary outcomes included psychosocial outcomes, family communication, and healthcare resource utilization. Participants were surveyed 2 and 4 weeks after results return and at 3-month intervals up to 1 year. RESULTS: Evolving outcome measures and standard of care presented critical challenges. The majority of participants in the UC arm received multi-gene panels [94.73%]. Rates of genetic findings supporting the diagnosis of hereditary CRCP were 7.5% [7/93] vs. 5.4% [5/93] in the CES and UC arms, respectively (P = 0.28). Differences in privacy concerns after receiving CRCP results were identified (0.88 in UC vs 0.38 in CES, P = 0.05); however, healthcare resource utilization, family communication and psychosocial outcomes were similar between the two arms. More participants with positive results (17.7%) intended to change their life insurance 1  month after the first return visit compared to participants returned a variant of uncertain significance (9.1%) or negative result (4.8%) (P = 0.09). CONCLUSION: Our results suggest that CES provides similar clinical benefits to multi-gene panels in the diagnosis of hereditary CRCP.

The Feelings About genomiC Testing Results (FACToR) Questionnaire: Development and Preliminary Validation.

The purpose of this study was to develop a brief instrument, the Feelings About genomiC Testing Results (FACToR), to measure the psychosocial impact of returning genomic findings to patients in research and clinical practice. To create the FACToR, we modified and augmented the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire based on findings from a literature review, two focus groups (N = 12), and cognitive interviews (N = 6). We evaluated data from 122 participants referred for evaluation for inherited colorectal cancer or polyposis from the New EXome Technology in (NEXT) Medicine Study, an RCT of exome sequencing versus usual care. We assessed floor and ceiling effects of each item, conducted principal component analysis to identify subscales, and evaluated each subscale's internal consistency, test-retest reliability, and construct validity. After excluding items that were ambiguous or demonstrated floor or ceiling effects, 12 items forming four distinct subscales were retained for further analysis: negative emotions, positive feelings, uncertainty, and privacy concerns. All four showed good internal consistency (0.66-0.78) and test-retest reliability (0.65-0.91). The positive feelings and the uncertainty subscales demonstrated known-group validity. The 12-item FACToR with four subscales shows promising psychometric properties on preliminary evaluation in a limited sample and needs to be evaluated in other populations.

Discordance in selected designee for return of genomic findings in the event of participant death and estate executor.

BACKGROUND: Legal and ethical questions arise regarding disseminating genetic research results to family members in the event of a research participant's death; failure to return or return to legal next of kin or estate executor may not reflect participant desires. We sought to determine participant preferences for whether and to whom they would like their data released in the case of their death prior to receiving genomic results, focusing on whether the person selected was also their estate executor. METHODS: The University of Washington NEXT Medicine Study of the Clinical Sequencing Exploratory Research program previously reported participant preferences regarding designating an individual to receive genomic results in the event of death, including whether they want results shared, and if so, with what person. Participants were also asked whether this designee is executor of their will or estate. RESULTS: To date, 61 individuals were asked about the concordance of their study designee and legal representative: 42 (69%) reported having a will or estate plan and of these, 14 (33%) chose someone other than their executor to receive their results. For the 14 who chose someone other than their estate executor to receive genetic results, 12 (86%) chose a family member, typically a biological relative, as their designee. Those with a different genomic designee than their executor were less likely to be partnered (P = 0.0024). For those partnered participants without an estate plan, spouses were not always chosen for return of genomic results. CONCLUSION: For one-third of our participants, the individual deemed most appropriate by the participant to receive their genomic results was not the executor. In the absence of an explicit designation, HIPAA may prohibit access to genomic results to persons other than the executor; hence asking for designation at the time of study enrollment (or initiation of clinical testing) is important.

Application of the PEN-3 Model to Tobacco Initiation, Use, and Cessation Among American Indian and Alaska Native Adults.

American Indian (AI) and Alaska Native (AN) communities confront some of the highest rates of tobacco use and its sequelae. As part of a formative research project investigating stakeholder understandings, preferences, and needs surrounding the use of pharmacogenetics toward tobacco cessation treatment, we sought to characterize sociocultural issues related to tobacco use and cessation. We used the PEN-3 cultural model to frame the research question and analysis of stakeholder interviews with 20 AI/AN patients, 12 health care providers, and 9 tribal leaders. Our study found high knowledge levels of the negative health effects of tobacco use; however, most patient participants ascribed negative health effects only to regular, heavy tobacco use and not to light use, which is more common in the population. The majority of patient participants did not endorse use of tobacco cessation treatment despite evidence of efficacy among AI/AN adults. Health promotion messaging to target low-tobacco consuming AI/AN people is needed. Additionally, messaging to promote tobacco cessation treatment using successful AI/AN former tobacco users to improve community perception of tobacco cessation treatment is recommended.

Patients' Choices for Return of Exome Sequencing Results to Relatives in the Event of Their Death.

The informed consent process for genetic testing does not commonly address preferences regarding disclosure of results in the event of the patient's death. Adults being tested for familial colorectal cancer were asked whether they want their exome sequencing results disclosed to another person in the event of their death prior to receiving the results. Of 78 participants, 92% designated an individual and 8% declined to. Further research will help refine practices for informed consent.

Views on electronic cigarette use in tobacco screening and cessation in an Alaska Native healthcare setting.

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.

Comparative effectiveness of next generation genomic sequencing for disease diagnosis: design of a randomized controlled trial in patients with colorectal cancer/polyposis syndromes.

Whole exome and whole genome sequencing are applications of next generation sequencing transforming clinical care, but there is little evidence whether these tests improve patient outcomes or if they are cost effective compared to current standard of care. These gaps in knowledge can be addressed by comparative effectiveness and patient-centered outcomes research. We designed a randomized controlled trial that incorporates these research methods to evaluate whole exome sequencing compared to usual care in patients being evaluated for hereditary colorectal cancer and polyposis syndromes. Approximately 220 patients will be randomized and followed for 12 months after return of genomic findings. Patients will receive findings associated with colorectal cancer in a first return of results visit, and findings not associated with colorectal cancer (incidental findings) during a second return of results visit. The primary outcome is efficacy to detect mutations associated with these syndromes; secondary outcomes include psychosocial impact, cost-effectiveness and comparative costs. The secondary outcomes will be obtained via surveys before and after each return visit. The expected challenges in conducting this randomized controlled trial include the relatively low prevalence of genetic disease, difficult interpretation of some genetic variants, and uncertainty about which incidental findings should be returned to patients. The approaches utilized in this study may help guide other investigators in clinical genomics to identify useful outcome measures and strategies to address comparative effectiveness questions about the clinical implementation of genomic sequencing in clinical care.

Reframing the goals of care conversation: "we're in a different place".

PURPOSE: Existing recommendations for communicating with patients with metastatic cancer about redefining goals of care when anticancer treatment is unlikely to provide benefit are based on limited evidence. This study was designed to elicit patient and family views on commonly used communication practices. STUDY DESIGN AND METHODS: Participants were 37 patients with metastatic gastrointestinal cancer and 20 bereaved family members who listened to audiorecordings of oncology fellows instructed to discuss a transition in goals of care with a standardized patient for whom evidence-based palliative chemotherapy was no longer effective. During semistructured qualitative interviews, participants commented on the audiorecordings to give feedback on what they liked or disliked about the oncologist's communication. These comments were transcribed and analyzed. RESULTS: Three preferred communication practices were identified from participants' comments. The first practice involves a necessary disruption of the patient's expectations about "trying another chemo" ("We're in a different place"). The second practice is offering actionable responses to the disruption ("Here's what we can do now"). The third practice is to find a new place that acknowledges death is closer yet still allows for "living forward" ("Use your inner wisdom"). CONCLUSION: This study of patient and family feedback indicates that patients and families perceive a conversation about goals of care to require disruption of an existing routine, followed by a process of searching and then reconfiguration, rather than a logical decision process. These findings suggest that assessing quality from patient perspectives must take into account a period of disruption and chaos.

Building partnerships in community-based participatory research: budgetary and other cost considerations.

Community-based participatory research (CBPR) is an important framework for partnering with communities to reduce health disparities. Working in partnership with community incurs additional costs, some that can be represented in a budget summary page and others that are tied to the competing demands placed on community and academic partners. These cost considerations can inform development of community-academic partnerships. We calculated costs from a case study based on an ongoing CBPR project involving a Community Planning Group (CPG) of community co-researchers in rural Alaska and a bicultural liaison group who help bridge communication between CPG and academic co-researchers. Budget considerations specific to CBPR include travel and other communication-related costs, compensation for community partners, and food served at meetings. We also identified sources of competing demands for community and academic partners. Our findings can inform budget discussions in community-academic partnerships. Discussions of competing demands on community partners' time can help plan timelines for CBPR projects. Our findings may also inform discussions about tenure and promotion policies that may represent barriers to participation in CBPR for academic researchers.

Silent loss and the clinical encounter: Parents' and physicians' experiences of stillbirth-a qualitative analysis.

BACKGROUND: In the United States, an estimated 70 stillbirths occur each day, on average 25,000 each year. Research into the prevalence and causes of stillbirth is ongoing, but meanwhile, many parents suffer this devastating loss, largely in silence, due to persistent stigma and taboo; and many health providers report feeling ill equipped to support grieving parents. Interventions to address bereavement after neonatal death are increasingly common in U.S. hospitals, and there is growing data on the nature of parent bereavement after a stillbirth. However, further research is needed to evaluate supportive interventions and to investigate the parent-clinician encounter during hospitalization following a stillbirth. Qualitative inquiry offers opportunities to better understand the lived experience of parents against the backdrop of clinicians' beliefs, intentions, and well-meaning efforts to support grieving parents. METHODS: We present a secondary qualitative analysis of transcript data from 3 semi-structured focus groups conducted with parents who had experienced a stillbirth and delivered in a hospital, and 2 focus groups with obstetrician-gynecologists. Participants were drawn from the greater Seattle region in Washington State. We examine parents' and physicians' experiences and beliefs surrounding stillbirth during the clinical encounter using iterative discourse analysis. RESULTS: Women reported that the cheery, bustling environment of the labor and delivery setting was a painful place for parents who had had a stillbirth, and that the well-meaning attempts of physicians to offer comfort often had the opposite effect. Parents also reported that their grief is deeply felt but not socially recognized. While physicians recognized patients' grief, they did not grasp its depth or duration. Physicians viewed stillbirth as an unexpected clinical tragedy, though several considered stillbirth less traumatic than the death of a neonate. In the months and years following a stillbirth, these parents continue to memorialize their children as part of their family. CONCLUSIONS: Hospitals need to examine the physical environment for deliveries and, wherever possible, offer designated private areas with staff trained in stillbirth care. Training programs in obstetrics need to better address the bereavement needs of parents following a stillbirth, and research is needed to evaluate effective bereavement interventions, accounting for cultural variation. Critical improvements are also needed for mental health support beyond hospitalization. Finally, medical professionals and parents can play an important role in reversing the stigma that surrounds stillbirth.

Genetics researchers' and IRB professionals' attitudes toward genetic research review: a comparative analysis.

PURPOSE: Genetic research involving human participants can pose challenging questions related to ethical and regulatory standards for research oversight. However, few empirical studies describe how genetic researchers and institutional review board (IRB) professionals conceptualize ethical issues in genetic research or where common ground might exist. METHODS: Parallel online surveys collected information from human genetic researchers (n = 351) and IRB professionals (n = 208) regarding their views about human participant oversight for genetic protocols. RESULTS: A range of opinions were observed within groups on most issues. In both groups, a minority thought it likely that people would be harmed by participation in genetic research or identified from coded genetic data. A majority of both groups agreed that reconsent should be required for four of the six scenarios presented. Statistically significant differences were observed between groups on some issues, with more genetic researcher respondents trusting the confidentiality of coded data, fewer expecting harms from reidentification, and fewer considering reconsent necessary in certain scenarios. CONCLUSION: The range of views observed within and between IRB and genetic researcher groups highlights the complexity and unsettled nature of many ethical issues in genome research. Our findings also identify areas where researcher and IRB views diverge and areas of common ground.

What patients value when oncologists give news of cancer recurrence: commentary on specific moments in audio-recorded conversations.

PURPOSE: Recommendations for communicating bad or serious news are based on limited evidence. This study was designed to understand patient perspectives on what patients value when oncologists communicate news of cancer recurrence. STUDY DESIGN AND METHODS: Participants were 23 patients treated for a gastrointestinal cancer at a tertiary U.S. cancer center within the past 2 years, who had semistructured qualitative interviews in which they listened to audio recordings of an oncology fellow discussing news of cancer recurrence with a standardized patient. Participants paused the audio recording to comment on what they liked or disliked about the oncologist's communication. RESULT: Three themes were identified that refine existing approaches to discussing serious news. The first theme, recognition, described how the oncologist responded to the gravity of the news of cancer recurrence for the patient. Participants saw the need for recognition throughout the encounter and not just after the news was given. The second theme, guiding, describes what participants wanted after hearing the news, which was for the oncologist to draw on her biomedical expertise to frame the news and plan next steps. The third theme, responsiveness, referred to the oncologist's ability to sense the need for recognition or guidance and to move fluidly between them. CONCLUSION: This study suggests that oncologists giving news of cancer recurrence could think of the communication as going back and forth between recognition and guidance and could ask themselves: "Have I demonstrated that I recognize the patient's experience hearing the news?" and "Have I provided guidance to the next steps?"

Attitudes toward genetic research review: results from a national survey of professionals involved in human subjects protection.

The recent expansion of human genetics research has raised complex ethical and regulatory issues. However, few published reports describe the views of professionals involved in human subjects protection (HSP) regarding the risks and benefits of genetic research. This anonymous, web-based study elicited the opinions of 208 HSP professionals about review of genetic research. The majority of respondents felt that different guidance is needed for various aspects of genetic protocol review compared with other types of human subjects research. Importantly, opinions were divided on specific genetic research issues, such as what constitutes human subjects research, when to re-consent, and the likelihood and risks of research participant identification. Findings from this study illustrate the need for a collaborative approach to ethics oversight in the review and conduct of genetic research.