Evaluation of mailed results versus telephone disclosure of normal cancer genetic test results in a low-risk underserved population.

Scalable models for result disclosure are needed to ensure large-scale access to genomics services. Research evaluating alternatives to genetic counseling suggests effectiveness; however, it is unknown whether these findings are generalizable across populations. We assessed whether a letter is non-inferior to telephone genetic counseling to inform participants with no personal or family history of cancer of their normal results. Data were collected via self-report surveys before and after result disclosure (at 1 and 6 months) in a study sample enriched for individuals from underserved populations. Primary outcomes were subjective understanding of results (global and aggregated) and test-related feelings, ascertained via three subscales (uncertainty, negative emotions, and positive feelings) of the Feelings About genomiC Testing Results (FACToR) measure. Secondary outcomes related to satisfaction with communication. Non-inferiority tests compared outcomes among disclosure methods. Communication by letter was inferior in terms of global subjective understanding of results (at 1 month) and non-inferior to telephoned results (at 6 months). Letter was non-inferior to telephone for aggregated understanding (at 6 months). Letter was superior (at 1 month) to telephone on the uncertainty FACToR subscale. Letter was non-inferior to telephone on the positive-feelings FACToR subscale (at 6 months). Letter was non-inferior to telephone for satisfaction with mode of result delivery and genetic test results. Communication via letter was inferior to telephone in communicating the "right amount of information." The use of written communication to relay normal results to low-risk individuals is a promising strategy that may improve the efficiency of care delivery.

Genetic counseling services delivered in the usual way­during clinic visits­can take up a lot of time for patients and genetic counselors. Alternatives to this practice have been studied among genetic counseling patients to spare genetic counselors' time and expand access and flexibility for patients. Yet, in these studies, the participants have lacked diversity. So, it is not known how these research findings pertain to all populations. In this study, we looked at the use of an alternative care model, a mailed letter, for sharing normal genetic test results with study participants from underserved populations. We tested whether patients viewed the mailed letter as no worse than a telephone conversation with a genetic counselor, which has been shown to be well received by patients. We learned that study participants felt they understood their results, were not distressed to receive the results, and were satisfied with how their results were delivered. Lastly, we found that participants were more satisfied with the amount of information provided about their test results during the telephone conversation compared with the mailed letter. This study provides new information about different ways to deliver test results to individuals receiving genetic services.

Refining a Multifaceted Model of Perceived Utility of Genomic Sequencing Results.

INTRODUCTION: Research on the perceived utility of genomic sequencing has focused primarily on pediatric populations and on individuals and families with rare genetic diseases. Here, we evaluate how well a multifaceted perceived utility model developed with these populations applies to a diverse, adult population aged 18-49 at risk for hereditary cancer and propose new considerations for the model. METHODS: Participants received clinical genomic sequencing in the Cancer Health Assessments Reaching Many (CHARM) study. Semi-structured qualitative interviews were conducted with a subset of participants at 1 and 6 months after results disclosure. We used an approach influenced by grounded theory to examine perceptions of the utility of genomic sequencing and analyzed how utility in CHARM mapped to the published multifaceted perceived utility model, noting which domains were represented or absent and which were most salient to our population. RESULTS: Participants' discussions of utility often involved multiple domains and revealed the variety of ways in which receiving sequencing results can impact one's life. Results demonstrated that an individual's perception of utility can change over the life course when sequenced at a relatively young age and may be influenced by the resources available to them to act on the results. CONCLUSION: Our findings demonstrate the relevance of a multifaceted perceived utility model for a diverse adult population at risk for hereditary cancer. We identified refinements that could make the model more robust, including emphasizing the overlapping nature of the domains and the importance of life stage and personal resources to the perception of utility.

Most people share genetic test results with relatives even if the findings are normal: Family communication in a diverse population.

PURPOSE: With increasing utilization of genetic testing, sharing genetic information can become part of general family health communication while providing biological relatives with important information about their own genetic risk. Importantly, little is known about motivations for and barriers to family communication of genetic information in historically underserved populations. METHODS: Using mixed methods, we explored patient experiences with family communication in a study population of English- and Spanish-speaking adults aged 18 to 49 years, enriched for participants from historically underserved backgrounds. Risk screening for hereditary cancer guided genetic testing for cancer risk genes and other medically actionable findings. RESULTS: Most participants overall (91%), including most with normal findings (89%), shared or planned to share their results with relatives. Common motivations for sharing results were to give relatives information about their genetic risk and because the participant thought the results were interesting. Reasons for not sharing were limited contact with relatives, perceptions of limited clinical utility for relatives, and concern that discussion of genetic information was stigmatized or taboo. CONCLUSION: Results demonstrate high rates of sharing genetic information, indicate motivations for sharing go beyond facilitating genetic testing for relatives, and suggest general willingness to share genetic information as part of family health communication.

The role of polygenic risk scores in breast cancer risk perception and decision-making.

Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information. We conducted an embedded Ethical, Legal, and Social Implications (ELSI) study to examine if and how unaffected participants in a US population breast cancer screening trial understood and utilized PRS, as part of a multifactorial risk score combining traditional risk factors with a genetic risk assessment, to make screening and risk-reduction decisions. Semi-structured qualitative interviews were conducted with 24 trial participants who were designated at elevated risk for breast cancer due to their combined risk score. Interviews were analyzed using a grounded theory approach. Participants understood PRS conceptually and accepted it as one of many risk factors to consider, yet the value and meaning they ascribed to this risk estimate varied. Most participants reported financial and insurance barriers to enhanced screening with MRI and were not interested in taking risk-reducing medications. These findings contribute to our understanding of how PRS may be best translated from research to clinical care. Furthermore, they illuminate ethical concerns about identifying risk and making recommendations based on polygenic risk in a population screening context where many may have trouble accessing appropriate care.

Medical interpreter-mediated genetic counseling for Spanish preferring adults at risk for a hereditary cancer syndrome.

The objective of this study was to identify interpretation challenges specific to exome sequencing and errors of potential clinical significance in the context of genetic counseling for adults at risk for a hereditary cancer syndrome. Thirty transcripts of interpreter-mediated telephone results disclosure genetic counseling appointments were coded for errors by bilingual researchers, and the coders applied an overall rating to denote the degree to which the errors interfered with communication overall. Genetic counselors reviewed a subset of errors flagged for potential clinical significance to identify those likely to have clinical impact. Qualitative interviews with 19 interpreters were analyzed to elucidate the challenges they face in interpreting for genetic counseling appointments. Our analysis identified common interpretation errors such as raising the register, omissions, and additions. Further, we found errors specific to genetic counseling concepts and content that appeared to impact the ability of the genetic counselor to accurately assess risk. These errors also may have impacted the patient's ability to understand their results, access appropriate follow-up care, and communicate with family members. Among interpreters' strengths was the use of requests for clarification; in fact, even more use of clarification would have been beneficial in these encounters. Qualitative interviews surfaced challenges stemming from the structure of interpreter work, such as switching from medical and nonmedical interpretations without substantial breaks. Importantly, while errors were frequent, most did not impede communication overall, and most were not likely to impact clinical care. Nevertheless, potentially clinically impactful errors in communication of genetics concepts may contribute to inequitable care for limited English proficient patients and suggest that additional training in genetics and specialization in healthcare may be warranted. In addition, training for genetic counselors and guidance for patients in working effectively with interpreters could enhance interpreters' transmission of complex genetic concepts.

An accessible, relational, inclusive, and actionable (ARIA) model of genetic counseling compared with usual care: Results of a randomized controlled trial.

PURPOSE: Effective approaches to communicate genomic information are needed to ensure equitable care. In a randomized controlled superiority trial, we tested a novel practice model that aims to make genetic counseling inclusive, by making the communication accessible, relational, and actionable (ARIA). METHODS: In total, 696 English- and Spanish-speaking patients aged 18 to 49 years, enriched for individuals from historically underserved backgrounds, were randomized in 1:1 ratio to ARIA or usual care. Primary outcomes were accuracy of recall, communication satisfaction, and perceived understanding. In total, 33 participants completed qualitative interviews. RESULTS: Recall and understanding were high for all participants. ARIA participants scored higher on the relationship scale of communication satisfaction (mean difference = 0.09, 95% CI = <0.01 to 0.17). Moderator analyses of communication satisfaction showed that those with lower health literacy reported less communication difficulty in ARIA and those using medical interpreters reported greater communication ease in ARIA. No significant difference was found on other primary and secondary outcomes. Qualitative data enhanced understanding of how and why ARIA can be effective. CONCLUSION: This study provides evidence that a genetic counseling intervention that focuses on specific communication skills to enhance relationship-building, patient engagement, and comprehension can be effective with all patients and may be especially valuable for patients of lower health literacy and Spanish-speakers who use a medical interpreter.

A qualitative study of unaffected ATM and CHEK2 carriers: How participants make meaning of 'moderate risk' genetic results in a population breast cancer screening trial.

Relatively little is known about experiences of individuals with a pathogenic variant in a moderately penetrant breast cancer gene, particularly those without a personal history of cancer. The WISDOM trial is testing a model of risk-based breast cancer screening that integrates genomic (nine genes and polygenic risk) and other risk factors. In the context of an embedded Ethical, Legal, and Social Implications (ELSI) study of WISDOM, we conducted qualitative interviews at two timepoints post-result disclosure with 22 ATM and CHEK2 carriers. Results disclosure and interview recordings were transcribed and analyzed using a grounded theory analysis framework. We found that participants minimized the significance of their results in comparison to BRCA; were surprised but not alarmed by the results in the absence of family history; did not fundamentally change their perception of their breast cancer risk despite the new genomic information; exhibited variable responses to WISDOM's screening and risk reduction recommendations; and shared test results with family but did not strongly encourage cascade testing. Participants viewed the results as having limited utility and responded accordingly. Our study offers important insights into how genetic test results for moderate-risk genes are received, understood, and acted upon in population screening context.

Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews.

BACKGROUND: Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral - a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study. METHODS: Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard. We conducted semi-structured interviews with participants about barriers and facilitators to tool use and overall tool acceptability; interviews were recorded and professionally transcribed. Transcripts were coded based on a codebook developed using inductive techniques, and coded excerpts were reviewed to identify overarching themes related to barriers and facilitators to family history self-assessment and acceptability of the study tool. RESULTS: Interviewees endorsed the tool as easy to navigate and understand. However, they described barriers related to family history information, literacy and language, and certain tool functions. Participants offered concrete, easy-to-implement solutions to each barrier. Despite experience barriers to use of the tool, most participants indicated that electronic family history self-assessment was acceptable or preferable in comparison to clinician-collected family history. CONCLUSIONS: Even for participants who experienced barriers to tool use, family history self-assessment was considered an acceptable alternative to clinician-collected family history. Barriers experienced could be overcome with minor adaptations to the current family history tool. TRIAL REGISTRATION: This study is a sub-study of the Cancer Health Assessments Reaching Many (CHARM) trial, ClinicalTrials.gov, NCT03426878. Registered 8 February 2018.

Factors that contribute to disparities in time to acute leukemia diagnosis in young people: an in depth qualitative interview study.

BACKGROUND: Racial and ethnic disparities in outcomes for Black and Hispanic children with acute leukemia have been well documented, however little is known about the determinants of diagnostic delays in pediatric leukemia in the United States. The primary objective of this study is to identify factors contributing to delays preceding a pediatric leukemia diagnosis. METHODS: This qualitative study utilized in-depth semi-structured interviews. Parents and/or patients within two years of receiving a new acute leukemia diagnosis were asked to reflect upon their family's experiences preceding the patient's diagnosis. Subjects were purposively sampled for maximum variation in race, ethnicity, income, and language. Interviews were analyzed using inductive theory-building and the constant comparative method to understand the process of diagnosis. Chart review was conducted to complement qualitative data. RESULTS: Thirty-two interviews were conducted with a diverse population of English and Spanish speaking participants from two tertiary care pediatric cancer centers. Parents reported feeling frustrated when their intuition conflicted with providers' management decisions. Many felt laboratory testing was not performed soon enough. Additional contributors to delays included misattribution of vague symptoms to more common diagnoses, difficulties in obtaining appointments, and financial disincentives to seek urgent or emergent care. Reports of difficulty obtaining timely appointments and financial concerns were disproportionately raised among low-income Black and Hispanic participants. Comparatively, parents with prior healthcare experiences felt better able to navigate the system and advocate for additional testing at symptom onset. CONCLUSIONS: While there are disease-related factors contributing to delays in diagnosis, it is important to recognize there are multiple non-disease-related factors that also contribute to delays. Evidence-based approaches to reduce outcome disparities in pediatric cancer likely need to start in the primary care setting where timeliness of diagnosis can be addressed.

Laboratory-related outcomes from integrating an accessible delivery model for hereditary cancer risk assessment and genetic testing in populations with barriers to access.

PURPOSE: This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools. METHODS: Patients from clinics that serve populations with access barriers, who are screened at risk for a hereditary cancer syndrome based on adapted family history collection tools (the Breast Cancer Genetics Referral Screening Tool and PREMM5), were offered exome-based panel testing for cancer risk and medically actionable secondary findings. We used descriptive statistics, electronic health record review, and inferential statistics to explore participant characteristics and results, consultations and actions related to pathogenic/likely pathogenic variants identified, and variables predicting category of findings, respectively. RESULTS: Of all the participants, 87% successfully returned a saliva kit. Overall, 5% had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Almost all (14/15, 93%) participants completed recommended consultations with nongenetics providers after an average of 17 months. The recommended actions (eg, breast magnetic resonance imaging) were completed by 17 of 25 participants. Participant personal history of cancer and PREMM5 score were each associated with the category of findings (history and colon cancer finding, Fisher's exact P = .02; history and breast cancer finding, Fisher's exact P = .01; PREMM5TM score; and colon cancer finding, Fisher's exact P < .001). CONCLUSION: This accessible model of hereditary cancer risk assessment and genetic testing yielded results that were often acted upon by patients and physicians.

Quality of life of colorectal cancer survivors participating in a pilot randomized controlled trial of physical activity trackers and daily text messages.

PURPOSE: There are over 1.3 million colorectal cancer (CRC) survivors in the USA, many of whom report lower health-related quality of life (HRQoL) years after treatment. This study aimed to explore the effect of digital health tools on HRQoL in CRC survivors. METHODS: We conducted a two-arm, randomized controlled trial of 42 subjects who had completed treatment for CRC. Participants in the intervention arm received a Fitbit Flex™ and daily text messages for 12 weeks. HRQoL was assessed as a secondary endpoint in both arms at enrollment and 12 weeks using the Medical Outcomes Study Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy-Colorectal (FACT-C). Survey score changes from enrollment to 12 weeks were compared between the two arms using independent t tests, and scores at enrollment and 12 weeks were compared using paired t tests. RESULTS: An increase in the FACT-C functional well-being subscale was observed in individuals in the intervention arm pre- to post-intervention (median difference, 2; interquartile range (IQR), 1, 4; P = .02). Although the between-group comparison was not statistically significant, no change in the functional well-being subscale was observed in the control arm (median difference, 0; IQR, 1, 1; P = .71). No other measures of HRQoL appeared to differ within arm across time points or between arms. CONCLUSION: A 12-week digital physical activity intervention may improve functional well-being among CRC survivors. Larger randomized studies are needed to determine if digital health tools improve functional well-being among CRC survivors and if this improvement can be sustained over time. TRIAL REGISTRATION: NCT02966054; registration date, November 17, 2016.

Development and evaluation of an exome sequencing training course for medical interpreters.

Aim: As genomic medicine reaches more diverse populations, there is an increased need for healthcare interpreters who understand and can effectively interpret genomics concepts. Methods: We designed a course for healthcare interpreters on exome sequencing to enhance their preparedness for genomic results disclosure appointments in the Cancer Health Assessments Reaching Many (CHARM) study and beyond. The course was evaluated via pre/post surveys and qualitative interviews. Results: 23 interpreters completed the course; 87% rated it as excellent/very good. Improved pre/post confidence interpreting for genetics appointments was statistically significant; pre/post knowledge was not. Interviews highlighted the need for more discussion time. Conclusion: While the course increased confidence interpreting for exome sequencing results appointments, suggested modifications could enhance knowledge and retention of key concepts.

"It's personalized, but it's still bucket based": The promise of personalized medicine vs. the reality of genomic risk stratification in a breast cancer screening trial.

Adaptive pragmatic clinical trials offer an innovative approach that integrates clinical care and research. Yet, blurring the boundaries between research and clinical care raises questions about how clinicians and investigators balance their caregiving and research roles and what types of knowledge and risk assessment are most valued. This paper presents findings from an ethnographic ELSI (Ethical, Legal, Social Implications) study of an innovative clinical trial of risk-based breast cancer screening that utilizes genomics to stratify risk and recommend a breast cancer screening commensurate with the assessed risk. We argue that the trial demonstrates a fundamental tension between the promissory ideals of personalized medicine, and the reality of implementing risk stratified care on a population scale. We examine the development of a Screening Assignment Review Board in response to this tension which allows clinician-investigators to negotiate, but never fully resolve, the inherent contradiction of 'precision population screening'.

The limits of personalization in precision medicine: Polygenic risk scores and racial categorization in a precision breast cancer screening trial.

Population-based genomic screening is at the forefront of a new approach to disease prevention. Yet the lack of diversity in genome wide association studies and ongoing debates about the appropriate use of racial and ethnic categories in genomics raise key questions about the translation of genomic knowledge into clinical practice. This article reports on an ethnographic study of a large pragmatic clinical trial of breast cancer screening called WISDOM (Women Informed to Screen Depending On Measures of Risk). Our ethnography illuminates the challenges of using race or ethnicity as a risk factor in the implementation of precision breast cancer risk assessment. Our analysis provides critical insights into how categories of race, ethnicity and ancestry are being deployed in the production of genomic knowledge and medical practice, and key challenges in the development and implementation of novel Polygenic Risk Scores in the research and clinical applications of this emerging science. Specifically, we show how the conflation of social and biological categories of difference can influence risk prediction for individuals who exist at the boundaries of these categories, affecting the perceptions and practices of scientists, clinicians, and research participants themselves. Our research highlights the potential harms of practicing genomic medicine using under-theorized and ambiguous categories of race, ethnicity, and ancestry, particularly in an adaptive, pragmatic trial where research findings are applied in the clinic as they emerge. We contribute to the expanding literature on categories of difference in post-genomic science by closely examining the implementation of a large breast cancer screening study that aims to personalize breast cancer risk using both common and rare genomic markers.

Community research collaboration to develop a promotores-based hereditary breast cancer education program for Spanish-speaking Latinas.

Breast cancer (BC) is the most common cancer in Latinas and the leading cause of cancer death. Latinas tend to be diagnosed at later stages, receive poorer quality care and have a higher risk of mortality than non-Latina White (NLW) women. Among women with a genetic predisposition to hereditary BC, genetic counseling can be beneficial. Latinas participate in genetic counseling at lower rates than NLW women. The goal of this study was to develop comprehensive, culturally appropriate materials for community health educators (promotores)-led hereditary BC education program for Spanish-speaking Latinas. We developed the curriculum through feedback from 7 focus groups, with a total of 68 participants (35 promotores and 33 community members). We used a mixed-methods approach that relied on quantitative analysis of survey questions and qualitative content analysis of the focus groups transcripts. Pre and post promotores' training survey responses suggested improvement in the promotores' cancer-related knowledge. Themes that emerged from the qualitative analyses were (i) barriers to health education and/or care; (ii) importance of educating the Latino community about BC and genetics and (iii) role of the promotores. Future research will further evaluate the impact of the program in promotores' knowledge and community members' screening behaviors.

Cancer Health Assessments Reaching Many (CHARM): A clinical trial assessing a multimodal cancer genetics services delivery program and its impact on diverse populations.

Advances in the application of genomic technologies in clinical care have the potential to increase existing healthcare disparities. Studies have consistently shown that only a fraction of eligible patients with a family history of cancer receive recommended cancer genetic counseling and subsequent genetic testing. Care delivery models using pre-test and post-test counseling are not scalable, which contributes to barriers in accessing genetics services. These barriers are even more pronounced for patients in historically underserved populations. We have designed a multimodal intervention to improve subsequent cancer surveillance, by improving the identification of patients at risk for familial cancer syndromes, reducing barriers to genetic counseling/testing, and increasing patient understanding of complex genetic results. We are evaluating this intervention in two large, integrated healthcare systems that serve diverse patient populations (NCT03426878). The primary outcome is the number of diagnostic (hereditary cancer syndrome) findings. We are examining the clinical and personal utility of streamlined pathways to genetic testing using electronic medical record data, surveys, and qualitative interviews. We will assess downstream care utilization of individuals receiving usual clinical care vs. genetic testing through the study. We will evaluate the impacts of a literacy-focused genetic counseling approach versus usual care genetic counseling on care utilization and participant understanding, satisfaction, and family communication. By recruiting participants belonging to historically underserved populations, this study is uniquely positioned to evaluate the potential of a novel genetics care delivery program to reduce care disparities.