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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.

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.

Objective To describe the training and early implementation of the ARIA model of genetic counseling (Accessible, Relational, Inclusive, Actionable). Methods As part of the Cancer Health Assessments Reaching Many (CHARM) study, an interdisciplinary workgroup developed the ARIA curriculum and trained genetic counselors to return exome sequencing results using the ARIA model. Curriculum The ARIA curriculum includes didactic elements, discussion, readings, role plays, and observations of usual care genetic counseling sessions. The ARIA model provides the skills and strategies needed for genetic counseling to be accessible to all patients, regardless of prior knowledge or literacy level; involves appropriate psychological and social counseling without overwhelming the patient with information; and leaves the patient with clear and actionable next steps. Conclusion With sufficient training and practice, the ARIA model appears to be feasible, with promise for ensuring that genetic counselors’ communication is accessible, relational, inclusive and actionable for the diverse patients participating in genomic medicine. Practice implications ARIA offers a coherent set of principles and strategies for effective communication with patients of all literacy levels and outlines specific techniques to practice and incorporate these skills into routine practice. The ARIA model could be integrated into genetic counseling training programs and practice, making genetic counseling more accessible and meaningful for all patients.

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.

BACKGROUND: Clinical genomic implementation studies pose challenges for informed consent. Consent forms often include complex language and concepts, which can be a barrier to diverse enrollment, and these studies often blur traditional research-clinical boundaries. There is a move toward self-directed, web-based research enrollment, but more evidence is needed about how these enrollment approaches work in practice. In this study, we developed and evaluated a literacy-focused, web-based consent approach to support enrollment of diverse participants in an ongoing clinical genomic implementation study. METHODS: As part of the Cancer Health Assessments Reaching Many (CHARM) study, we developed a web-based consent approach that featured plain language, multimedia, and separate descriptions of clinical care and research activities. CHARM offered clinical exome sequencing to individuals at high risk of hereditary cancer. We interviewed CHARM participants about their reactions to the consent approach. We audio recorded, transcribed, and coded interviews using a deductively and inductively derived codebook. We reviewed coded excerpts as a team to identify overarching themes. RESULTS: We conducted 32 interviews, including 12 (38%) in Spanish. Most (69%) enrolled without assistance from study staff, usually on a mobile phone. Those who completed enrollment in one day spent an average of 12 minutes on the consent portion. Interviewees found the information simple to read but comprehensive, were neutral to positive about the multimedia support, and identified increased access to testing in the study as the key difference from clinical care. CONCLUSIONS: This study showed that interviewees found our literacy-focused, web-based consent approach acceptable; did not distinguish the consent materials from other online study processes; and valued getting access to testing in the study. Overall, conducting empirical bioethics research in an ongoing clinical trial was useful to demonstrate the acceptability of our novel consent approach but posed practical challenges.

PURPOSE: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. Disparities in research populations persist, however, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into design and implementation of genomics research has yet to be realized. METHODS: The NIH-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination. RESULTS: Projects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle. CONCLUSION: Each CSER project utilized more than one approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value-added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research.

This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools.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 PREMMOf 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 PREMMThis accessible model of hereditary cancer risk assessment and genetic testing yielded results that were often acted upon by patients and physicians.

Hereditary cancer syndromes result from germline genetic alterations predisposing individuals to higher lifetime cancer risk than the general population. Hereditary cancer syndromes account for 5%-10% of all malignancies and are characterized by early-onset, aggressive tumors affecting multiple tissue types.1 For example, patients with hereditary breast and ovarian cancer syndrome (HBOC) have high lifetime risk of breast (41%-90%) and ovarian (8%-62%) cancers and elevated risk for several other cancers.2 Similarly, patients with Lynch syndrome (LS) have high lifetime risk of colorectal (12%-52%) and endometrial (0%-57%) cancers, as well as other cancers.3 Reduced cost of genetic technologies4 and new guidance on collecting family history in primary care5 have enabled better detection of these syndromes, providing opportunities to reduce cancer risk. CONTEXT Key Objective Individuals with hereditary cancer syndromes are predisposed to higher lifetime cancer risk than the general population. Early diagnosis of these syndromes can lead to downstream care that greatly reduces cancer morbidity and mortality. In this narrative review, we explore the factors affecting uptake of and adherence to hereditary cancer risk reduction strategies and how these factors interact with systemic barriers to care in medically marginalized populations. Knowledge Generated We identified factors at the health system, clinician, and patient levels that interact to affect downstream hereditary cancer care and have implications for health equity. We found that several interventions designed to improve downstream care utilization did not address systemic barriers affecting marginalized populations and suggest strategies to address these barriers in future intervention design. Relevance Our review creates a template for the design of more equitable interventions to improve downstream hereditary cancer care.

Aim: To increase Spanish speakers' representation in genomics research, accessible study materials on genetic topics must be made available in Spanish. Materials & methods: The Clinical Sequencing Evidence-Generating Research consortium is evaluating genome sequencing for underserved populations. All sites needed Spanish translation of recruitment materials, surveys and return of results. Results: We describe our process for translating site-specific materials, as well as shared measures across sites, to inform future efforts to engage Spanish speakers in research. Conclusion: In translating and adapting study materials for roughly 1000 Spanish speakers across the USA, and harmonizing translated measures across diverse sites, we overcame numerous challenges. Translation should be performed by professionals. Studies must allocate sufficient time, effort and budget to translate and adapt participant materials.

e18565 Background: Diagnosis of hereditary cancers by genetic testing (GT) has significant implications for treatment decisions for individuals and risk reduction among family members. Recent guidelines have expanded the eligibility criteria for GT. However, significant disparities in GT completion persist based on race, ethnicity, insurance status, and English proficiency. Thus, novel interventions are needed to provide diverse populations equitable access to GT. Methods: From March to October 2021, we conducted a single arm study of a genetic testing station (GTS) intervention in a safety net hospital. The GTS intervention included (1) screening of clinic schedules for eligible patients; (2) video-based GT education in English, Spanish, and Cantonese; (3) consent for GT and collection of a blood or saliva sample by a genetic counseling assistant; (4) telehealth-based post-test counseling with a genetic counselor (GC). Bilingual, culturally concordant staff developed the educational videos and study materials. Patients who met the NCCN criteria for GT were eligible. We compared this group to a historical cohort who initiated GT in the preceding nine months. The historical cohort underwent GT in a traditional model: (1) oncologist-initiated referral, (2) pretest counseling with a GC, (3) GT if appropriate, and (4) post-test counseling to review and discuss results. Our primary outcomes were accessibility and feasibility assessed by tracking the implementation process. Secondary outcomes included completion rates of GT and post-test GC visit, and time from enrollment to GT result disclosure. We evaluated all associations with Chi-square tests for categorical variables and Pearson’s Chi-square test of medians for time to post-test visit. Results: We approached 92 patients for GTS; 3 declined, 89 patients underwent the GTS intervention. Of 155 patients (GTS: n = 89, historical cohort: n = 66), 15% were Black, 28% Asian, 17% White, 31% Hispanic/Latinx, 2% Native Hawaiian/Pacific Islander, and 7% multiethnic/other; 51% spoke English, 27% Spanish, 17% Cantonese, and 5% other. In the GTS cohort, 85 (96%) of participants completed GT and 80 (90%) completed the post-test GC visit, compared to 46 (70%, p < 0.001) and 42 (64%, p < 0.001) respectively in the historical cohort. The median time to result disclosure was 30.5 days (IQR 23.8 - 38.8) for the GTS cohort and 80.5 days (IQR 37.5 - 137.5, p = 0.001) for the historical cohort. Conclusions: Implementation of GTS was feasible and acceptable in a safety net setting. GTS resulted in more patients completing GT and post-test counseling and significantly reduced the time to result disclosure, which has the potential to impact treatment decisions and outcomes. As GT eligibility criteria broaden, innovative interventions, workflows, and tailored educational resources for diverse populations are needed to ensure equitable access to GT.

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

Genomic sequencing results need to be effectively communicated across all populations and practice settings. Projects in the Clinical Sequencing Evidence-Generating Research (CSER) consortium enroll diverse racial/ethnic and medically underserved participants across various clinical contexts. This article explores a set of CSER results disclosure cases to expand the evidence base on experiences returning genomic results. Case details were collected using a structured set of questions. We identified common themes in the case set, and assessed challenges and strategies in achieving six relevant results disclosure objectives. CSER-affiliated patient/community stakeholder impressions of the findings were solicited via video conference calls. Seventeen cases across six CSER projects were included. Case themes sorted into four categories: (1) factors influencing participant understanding, (2) participant emotional response, (3) disease burden, and (4) logistical challenges. Challenges meeting results disclosure objectives included a lack of dialogue, health literacy level, unexpected findings, and complex concepts. Strategies were consistent with traditional genetic counseling practice, but also highlighted approaches being evaluated in CSER projects. Patient/community stakeholders supported the identified themes and provided additional suggestions to improve patient understanding and engagement. These experiences add valuable insights into adapting genomic results disclosure practices to best serve all patient populations.

The descriptor 'usual care' refers to standard or routine care. Yet, no formal definition exists. The need to define what constitutes usual care arises in clinical research. Often one arm in a trial represents usual care in comparison with a novel intervention. Accordingly, usual care in genetic counseling research appears predominantly in randomized controlled trials. Recent standards for reporting genetic counseling research call for standardization, but do not address usual care. We (1) inventoried all seven studies in the Clinical Sequencing Evidence-Generating Consortium (CSER) about how genetic counseling was conceptualized, conducted, and whether a usual care arm was involved; (2) conducted a review of published randomized control trials in genetic counseling, comparing how researchers describe usual care groups; and (3) reviewed existing professionally endorsed definitions and practice descriptions of genetic counseling. We found wide variation in the content and delivery of usual care. Descriptions frequently detailed the content of usual care, most often noting assessment of genetic risk factors, collecting family histories, and offering testing. A minority included addressing psychological concerns or the risks versus benefits of testing. Descriptions of how care was delivered were vague except for mode and type of clinician, which varied. This significant variation, beyond differences expected among subspecialties, reduces the validity and generalizability of genetic counseling research. Ideally, research reflects clinical practice so that evidence generated can be used to improve clinical outcomes. To address this objective, we propose a definition of usual care in genetic counseling research that merges common elements from the National Society of Genetic Counselors' practice definition, the Reciprocal Engagement Model, and the Accreditation Council for Genetic Counselors' practice-based competencies. Promoting consistent execution of usual care in the design of genetic counseling trials can lead to more consistency in representing clinical care and facilitate the generation of evidence to improve it.

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.

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.

Introduction:Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.Methods:A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.Results:Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.Conclusions:In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.

Purpose: Genetic counseling (GC) and testing for hereditary breast/ovarian cancer (HBOC) is concentrated in elite medical centers and not offered in most public hospitals despite comparable risk across income levels. GC may be extended remotely by phone or video to patients in low resource settings, but the benefits and harms of these modes for these patients are unknown. Methods: We conducted a multicenter partially randomized preference noninferiority trial in 3 public hospitals to compare the effectiveness of 3 GC modes (in-person, phone, video) among 679 diverse patients at high-risk for HBOC. To answer some of our most important questions (e.g. How engaged are patients with counselors and how does that affect outcomes? What about the GC affects key message recall? How do patients' life/health contexts affect GC impact? How do these dynamics differ by GC mode?), we compiled 23 case studies (CS) for a multifaceted understanding of patient context, intended to reveal influences that may be subtle, complex, and not accessible from individual self-report. The main trial outcome was presented at AACR 2020; here we report the case studies methods and findings. CS participants had consented to audio-recording their GC sessions; agreed to be contacted for further research during the final trial survey; and had been offered genetic testing but did not have results at the time of the in-depth CS interview. An iterative analytic process integrated and summarized qualitative and quantitative data from surveys, interviews, genetic counselor reflections and audio recordings for each case including: patient demographics, health literacy rating, GC mode; GC session duration, key points, and engagement; genetic counselor reflections; interview highlights; general conclusions about that case; conclusions based on mode; patient quotes; and an integrated conclusion from all the data elements. Results: Our randomized trial produced equivalent outcomes across 3 GC modes. But our case studies revealed critical differences including higher quality engagement and trust-building via in-person and video counseling compared with phone, where distractions and brevity were common. While more patients opted for the convenience of phone, and for many it was their only option due to work and other demands, those counseled by phone were least likely to complete genetic testing when it was offered. Patients in all modes struggled with information recall. Conclusions: GC by phone is an important source of access for low-income patients but research should strive for higher quality. GC by video holds promise but availability is a concern. For both remote modes, easy access to testing is required. Strategies to improve information recall are needed in all modes. Research using quantitative cognitive ascertainment should include mixed methods for a more multifaceted in-depth exploration that yields rich real-world insights. Citation Format: Rena J. Pasick, Claudia Guerra, Selina R. Flores, Galen Joseph. Blending research paradigms and methods to compare 3 modes of cancer genetic counseling with diverse public hospital patients: Insights from case studies [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-051.

Background: Underserved breast cancer survivors are typically offered fewer opportunities to participate in cancer research. To address this disparity, a community based navigator program, Shanti's Margot Murphy Breast Cancer Program (Shanti) initiated a collaboration with UCSF researchers and BreastCancerTrials.org (BCT), a nonprofit clinical trials matching service to explore the potential role of a trusted community-based organization as a source of culturally appropriate education and access to clinical trial information. Through formative research, we developed the Health Research Engagement Intervention (HREI), a one-on-one navigator-client education session emphasizing the range of treatment and non-treatment quality-of-life and observational studies, conducted at a time when the participant is not in the initial crisis of diagnosis. The HREI ends by providing participants with an information card listing BCT and other organizations that provide information about health research for breast cancer patients and survivors. Methods: We tested the HREI in a randomized controlled trial, comparing the HREI to simply providing the information card. Pre and post intervention surveys one month apart measured our primary outcome of health research information-seeking behavior. Secondary outcomes include health research knowledge, attitudes towards research participation, and health empowerment. All Shanti clients who spoke English, Cantonese or Spanish and had “low care navigation needs” (either completed treatment or no longer in the crisis of initial diagnosis and/or burdened by treatment protocols) were eligible. Results: We recruited 133 Shanti Clients, including 59 who spoke English, 48 Cantonese, and 26 Spanish; 66 were randomized to the intervention arm and 67 to the control arm, and 130 completed both pre- and post-test surveys. Almost one-third of participants in both the intervention and control arms reported having talked to someone about health research or having called a telephone number or visited a website listed on the card (30% vs. 30%, p=0.94); a smaller proportion of participants confirmed that their information-seeking was related to the content of the educational materials (17% vs. 9%, p=0.22). On average the change from pre- to post-test in a 5-item knowledge score, adjusted for pre-test knowledge, was greater in the intervention group than in the control group (p=0.028), but the proportion of participants who were very confident that they could find health research information (had health empowerment) remained essentially unchanged in both study arms (intervention: 20% post vs. 21% pre, p=0.76; control: 25% post vs. 25% pre, p=1.00). Women were more likely to seek information if they had higher pre-test knowledge scores (odds ratio [OR]=3.5 per item, 95% confidence interval [CI] 1.5-8.4) or a greater increase in knowledge from pre- to post-test (OR=2.2 per item, 95% CI 1.1-4.7); there was no association between information-seeking and health empowerment (OR=0.6, 95% CI 0.2-2.5) or study arm (OR=1.6, 95% CI 0.5-4.9). Conclusion: The HREI had a positive impact on knowledge of health research but did not significantly affect health empowerment or health research information-seeking behavior. Citation Format: Joseph G, Nickell A, Cohen E, Burke NJ, Colen S, Lawlor K, Guerra C, Stewart SL. Engaging linguistically and ethnically diverse low income women in health research: A randomized controlled trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-05.

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.

This abstract was withdrawn by the authors.

Purpose This study describes challenges faced while incorporating sometimes conflicting stakeholder feedback into study design and development of patient-facing materials for a translational genomics study aiming to reduce health disparities among diverse populations. Methods We conducted an ethnographic analysis of study documents including summaries of patient advisory committee meetings and interviews, reflective field notes written by study team members, and correspondence with our institutional review board (IRB). Through this analysis, we identified cross-cutting challenges for incorporating stakeholder feedback into development of our recruitment, risk assessment, and informed consent processes and materials. Results Our analysis revealed three key challenges: (1) balancing precision and simplicity in the design of study materials, (2) providing clinical care within the research context, and (3) emphasizing potential study benefits versus risks and limitations. Conclusion While involving patient stakeholders in study design and materials development can increase inclusivity and responsiveness to patient needs, patient feedback may conflict with that of content area experts on the research team and IRBs who are tasked with overseeing the research. Our analysis highlights the need for further empirical research about ethical challenges when incorporating patient feedback into study design, and for dialogue with genomic researchers and IRB representatives about these issues.

Objective Evaluate a community-based navigator intervention to increase breast cancer patients’ and survivors’ access to information about health research participation opportunities. Methods In the context of a Community Based Participatory Research collaboration, we conducted a prospective randomized controlled trial of the Health Research Engagement Intervention with pre- and post-intervention surveys (n = 133). The primary outcome was health research information-seeking behavior. Secondary outcomes were health research knowledge, willingness to participate in health research, and health empowerment. Qualitative interviews (n = 11) elucidated participant perspectives on the intervention. Results There was no statistically significant difference between intervention and control groups’ information-seeking behavior. Knowledge that not all health research studies are about drugs or treatments increased significantly from pre- to post-test among intervention group participants (32% to 48%, p = 0.012), but not in the control group (43% to 30%, p = 0.059); the difference between arms was statistically significant (p = 0.0012). Although survey responses indicated willingness to participate, qualitative interviews identified competing priorities that limited participants’ motivation to seek enrollment information. Conclusions and Practice Implications Community-based navigators are a trusted, and therefore promising link between health research and low-income underserved communities. However, systemic barriers in health research infrastructures need to be addressed to include low income, LEP and immigrant populations.

Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.

In public health settings, where availability of genetic counseling (GC) and testing for hereditary breast and ovarian cancer is limited, telehealth could expand access to academic centers where these services are concentrated. However, little is known about the effectiveness of remote modes for ethnically diverse and low health literacy patients. Methods. From 2017-20 UCSF researchers partnered with 3 public hospitals to conduct a partially randomized preference noninferiority trial with English-, Spanish-, and Cantonese-speaking patients with strong personal and/or family history of cancer. Participants received GC in person, by phone, or via video. Pre- and post-GC telephone surveys measured study outcomes: knowledge, cancer- specific distress, decisional conflict, risk perception, and satisfaction. A subset of 23 participants was recruited for case studies (CS) to elucidate quantitative findings. CS integrated patient and counselor in-depth interviews, GC session transcripts, and survey and tracking data for a multi-dimensional understanding of each individual’s GC experience. Results. Among 23,633 family history forms collected, 1,574 patients were eligible; 1404 were reached and 708 consented. Of 394 randomized, 322 attended GC and 312 completed the final survey. After GC, mean knowledge scores increased, and cancer-specific distress and decisional conflict decreased overall. Counseling attendance varied significantly by assigned mode (75% via video at a clinic, 77% in person, and 92% by phone), but the modes yielded noninferior outcomes. Respondents overwhelmingly rated all modes as “very convenient” and satisfaction with counseling as “very high.” Compared with baseline, knowledge increased significantly regardless of mode. However, this increase was significantly less for African Americans and for those with less education (with each adjusted for the other) across all modes. Completion of genetic testing (GT) was the inverse of counseling attendance: 94% in person, 93% video, and 65% by phone. Case studies (CS) revealed the complexities of counseling public hospital patients. Phone patients valued the access despite connection issues, but phone appointments tended to be briefer, and qualitative interviews suggested that communication was less effective by phone. While many phone patients said they would not be able to access GC any other way, several felt they would get more out it in person. Importantly, GT was offered on the spot to in-person patients while some counseled by phone had second thoughts and other barriers. CS of video counseling found benefits similar to in-person GC such as use of visual cues and formation of meaningful connections. Conclusion. Our findings indicate that GC can be delivered to high-risk public hospital patients remotely by phone, video, or in-person in order to fill a gap in access to critical genetic services. Further research is needed to achieve optimal outcomes for all patients and to increase the rate of testing for those counseled by phone. Citation Format: Rena J Pasick, Susan L. Stewart, Robin Lee, Claudia Guerra, Celia Kaplan, Galen Joseph, Selina Flores, Janice Tsoh, Niharika Dixit, Miya Frick, Heather Cedermaz, Lily Wong, Amal Khoury, Brittany Campbell. Genetic counseling for high-risk public hospital patients: A randomized and preference-based trial compares delivery in person, by phone, and video [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-051.

Genetic and genomic testing is reaching more people than ever, yet disparities in access to and application of hereditary cancer screening remain. Further, with the advent of lower cost sequencing, the amount and complexity of information that is conveyed to patients, including secondary results, has increased. As part of the Clinical Sequencing Evidence-Generating Research (CSER) consortium, the Cancer Health Assessments Reaching Many (CHARM) study implemented a hereditary cancer risk assessment program for healthy adults aged 18-49. Participants were recruited in English and Spanish from two primary care settings (Kaiser Permanente Northwest and Denver Health). Participants underwent clinical exome sequencing and were randomized to receive their test results via usual care or a “literacy-focused” genetic counseling approach (n=845). Genetic counselors in the literacy- focused arm received in-depth training to adapt and apply evidence-based methods for effective communication with individuals of all literacy levels. We hypothesized that the literacy-focused approach would be non-inferior to usual care genetic counseling and generate higher satisfaction, engagement, and understanding of and adherence to recommended care. We also collected qualitative data to explore the experience of receiving exome sequencing results in this setting. Here, we present findings from qualitative interviews with participants conducted within a month (n=35) and again at 6 months (n=15) after receiving results, including: pathogenic cancer risk variants, medically actionable secondary findings and carrier results; variants of uncertain significant (VUS) in cancer genes; and negative results. The mean age of participants was 33. 72% spoke English and 75% were considered medically underserved by CHARM criteria. Participants in both trial arms expressed overall satisfaction; however, some participants in the literacy-focused arm indicated that specific elements of the approach, such as teach-back and plain language, helped facilitate their understanding, while some in the usual care arm said the information was overly technical. Younger participants in both arms, whose sequencing results will not be clinically actionable for many years, reported less worry and recalled fewer details about their results than older participants. While participants recognized the utility of positive results for family, at six months only some had spoken with them about testing, and few relatives had undergone cascade testing offered by CHARM. Genomic medicine requires clear communication of disease risk and prevention recommendations. Our qualitative findings suggest that the literacy-focused approach to genetic counseling can help facilitate patient understanding of cancer and other genomic risk. These results can guide effective disclosure of sequencing results and have implications for training clinical genetics professionals in the provision of equitable care for diverse patients. Citation Format: Leslie Riddle, Laura M. Amendola, Marian J. Gilmore, Brad Rolf, Jamilyn Zepp, Claudia Guerra, Barbara Biesecker, Mikaella Caruncho, Katherine P. Anderson, Alan F. Rope, Tia L. Kauffman, Hannah Lewis, Stephanie A. Kraft, Devan M. Duenas, Benjamin Wilfond, Katrina A.B. Goddard, Galen Joseph. Reducing disparities in genomic medicine using a literacy-focused genetic counseling model for cancer risk assessment [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-050.