Protecting Privacy of Pregnant and LGBTQ+ Research Participants.

This Viewpoint summarizes existing federal regulations aimed at protecting research data, describes the challenges of enforcing these regulations, and discusses how evolving privacy technologies could be used to reduce health disparities and advance health equity among pregnant and LGBTQ+ research participants.

Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real-World Patient Data.

PURPOSE: Although immune checkpoint inhibitors (ICIs) have improved outcomes in certain patients with cancer, they can also cause life-threatening immunotoxicities. Predicting immunotoxicity risks alongside response could provide a personalized risk-benefit profile, inform therapeutic decision making, and improve clinical trial cohort selection. We aimed to build a machine learning (ML) framework using routine electronic health record (EHR) data to predict hepatitis, colitis, pneumonitis, and 1-year overall survival. METHODS: Real-world EHR data of more than 2,200 patients treated with ICI through December 31, 2018, were used to develop predictive models. Using a prediction time point of ICI initiation, a 1-year prediction time window was applied to create binary labels for the four outcomes for each patient. Feature engineering involved aggregating laboratory measurements over appropriate time windows (60-365 days). Patients were randomly partitioned into training (80%) and test (20%) sets. Random forest classifiers were developed using a rigorous model development framework. RESULTS: The patient cohort had a median age of 63 years and was 61.8% male. Patients predominantly had melanoma (37.8%), lung cancer (27.3%), or genitourinary cancer (16.4%). They were treated with PD-1 (60.4%), PD-L1 (9.0%), and CTLA-4 (19.7%) ICIs. Our models demonstrate reasonably strong performance, with AUCs of 0.739, 0.729, 0.755, and 0.752 for the pneumonitis, hepatitis, colitis, and 1-year overall survival models, respectively. Each model relies on an outcome-specific feature set, though some features are shared among models. CONCLUSION: To our knowledge, this is the first ML solution that assesses individual ICI risk-benefit profiles based predominantly on routine structured EHR data. As such, use of our ML solution will not require additional data collection or documentation in the clinic.

Participant-guided development of bilingual genomic educational infographics for Electronic Medical Records and Genomics Phase IV study.

OBJECTIVE: Developing targeted, culturally competent educational materials is critical for participant understanding of engagement in a large genomic study that uses computational pipelines to produce genome-informed risk assessments. MATERIALS AND METHODS: Guided by the Smerecnik framework that theorizes understanding of multifactorial genetic disease through 3 knowledge types, we developed English and Spanish infographics for individuals enrolled in the Electronic Medical Records and Genomics Network. Infographics were developed to explain concepts in lay language and visualizations. We conducted iterative sessions using a modified "think-aloud" process with 10 participants (6 English, 4 Spanish-speaking) to explore comprehension of and attitudes towards the infographics. RESULTS: We found that all but one participant had "awareness knowledge" of genetic disease risk factors upon viewing the infographics. Many participants had difficulty with "how-to" knowledge of applying genetic risk factors to specific monogenic and polygenic risks. Participant attitudes towards the iteratively-refined infographics indicated that design saturation was reached. DISCUSSION: There were several elements that contributed to the participants' comprehension (or misunderstanding) of the infographics. Visualization and iconography techniques best resonated with those who could draw on prior experiences or knowledge and were absent in those without. Limited graphicacy interfered with the understanding of absolute and relative risks when presented in graph format. Notably, narrative and storytelling theory that informed the creation of a vignette infographic was most accessible to all participants. CONCLUSION: Engagement with the intended audience who can identify strengths and points for improvement of the intervention is necessary to the development of effective infographics.

Incidence of Adolescent Syncope and Related Injuries Following Vaccination and Routine Venipuncture.

PURPOSE: Vaccination is associated with syncope in adolescents. However, incidence of vaccine-associated syncope and resulting injury, and how it compares to syncope incidence following other medical procedures, is not known. Here, we describe the incidence of syncope and syncope-related injury in adolescents following vaccination and routine venipuncture. METHODS: We identified all Kaiser Permanente Northwest members ages 9-18 years with a vaccination or routine venipuncture and a same-day International Classification of Diseases diagnosis of syncope from 2013 through 2019. All cases were chart reviewed to establish chronology of events (vaccination, venipuncture, syncope, and injury, as applicable) and to attribute cause to vaccination or venipuncture. Incidence rates for vaccine-associated and venipuncture-associated syncope were calculated overall, by sex and age group. Syncope events resulting in injury were assessed for each event type. RESULTS: Of 197,642 vaccination and 12,246 venipuncture events identified, 549 vaccination and 67 venipuncture events had same-day syncope codes. Chart validation confirmed 59/549 (10.7%) events as vaccine-associated syncope, for a rate of 2.99 per 10,000 vaccination events (95% confidence interval (CI): 2.27-3.85) and 20/67 (29.9%) events as venipuncture-associated syncope, for a rate of 16.33 per 10,000 venipuncture events (95% CI: 9.98-25.21). The incidence rate ratio of vaccine-associated to venipuncture-associated syncope events was 0.18 (95% CI: 0.11-0.31). The incidence of vaccine-associated syncope increased with each additional simultaneously administered vaccine, from 1.51 per 10,000 vaccination events (95% CI: 0.93-2.30) following a single vaccine to 9.94 per 10,000 vaccination events (95% CI: 6.43-14.67) following three or more vaccines. Syncope resulted in injury in about 15% of both vaccine and venipuncture events. DISCUSSION: Syncope occurs more commonly following venipuncture than vaccination. The number of simultaneously administered vaccines is a risk factor for postvaccination syncope in adolescents.

Conducting inclusive research in genetics for transgender, gender-diverse, and sex-diverse individuals: Case analyses and recommendations from a clinical genomics study.

A person's phenotypic sex (i.e., endogenous expression of primary, secondary, and endocrinological sex characteristics) can impact crucial aspects of genetic assessment and resulting clinical care recommendations. In studies with genetics components, it is critical to collect phenotypic sex, information about current organ/tissue inventory and hormonal milieu, and gender identity. If researchers do not carefully construct data models, transgender, gender diverse, and sex diverse (TGSD) individuals may be given inappropriate care recommendations and/or be subjected to misgendering, inflicting medical and psychosocial harms. The recognized need for an inclusive care experience should not be limited to clinical practice but should extend to the research setting, where researchers must build an inclusive experience for TGSD participants. Here, we review three TGSD participants in the Family History and Cancer Risk Study (FOREST) to critically evaluate sex- and gender-related survey measures and associated data models in a study seeking to identify patients at risk for hereditary cancer syndromes. Furthermore, we leverage these participants' responses to sex- and gender identity-related questions in FOREST to inform needed changes to the FOREST data model and to make recommendations for TGSD-inclusive genetics research design, data models, and processes.

Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study.

BACKGROUND: Genetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services. METHODS: CHARM was implemented in Kaiser Permanente Northwest (KPNW) and Denver Health (DH) between 2018 and 2020. We identified post-testing screening (mammography, breast MRI, colonoscopy) and surgical (mastectomy, oophorectomy) procedures using electronic health records. We examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines. RESULTS: CHARM participants were followed for an average of 15.4 months (range: 0.4-27.8 months) after results disclosure. Less than 2% (11/680) received actionable risk management recommendations (i.e., could be completed in the initial years following testing) based on their test result. Among those who received actionable recommendations, risk management utilization was moderate (54.5%, 6/11 completed any procedure) and varied by procedure (mammogram: 0/3; MRI: 2/4; colonoscopy: 4/5; mastectomy: 1/5; oophorectomy: 0/3). Cancer screening and surgery procedures were rare in participants without actionable recommendations. CONCLUSION: Though the number of participants who received actionable risk management recommendations was small, our results suggest that implementing CHARM's risk assessment and testing model increased access to evidence-based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging risk management overuse.

Longitudinal adherence to breast cancer surveillance following cancer genetic testing in an integrated health care system.

PURPOSE: Screening with mammography and breast magnetic resonance imaging (MRI) is an important risk management strategy for individuals with inherited pathogenic variants (PVs) in genes associated with increased breast cancer risk. We describe longitudinal screening adherence in individuals who underwent cancer genetic testing as part of usual care in a vertically integrated health system. METHODS: We determined the proportion time covered (PTC) by annual mammography and breast MRI for individuals with PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, and ATM. We determined time covered by biennial mammography beginning at age 50 years for individuals who received negative results, uncertain results, or with PVs in genes without specific breast cancer screening recommendations. RESULTS: One hundred and forty individuals had PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, or ATM. Among these individuals, average PTC was 48% (range 0-99%) for annual screening mammography and 34% (range 0-100%) for annual breast MRI. Average PTC was highest for individuals with PVs in CHEK2 (N = 14) and lowest for individuals with PVs in TP53 (N = 3). Average PTC for biennial mammography (N = 1,027) was 49% (0-100%). CONCLUSION: Longitudinal screening adherence in individuals with PVs in breast cancer associated genes, as measured by the proportion of time covered, is low; adherence to annual breast MRI falls below that of annual mammography. Additional research should examine screening behavior in individuals with PVs in breast cancer associated genes with a goal of developing interventions to improve adherence to recommended risk management.

Evaluating cancer genetic services in a safety net system: overcoming barriers for a lasting impact beyond the CHARM research project.

Underserved patients face substantial barriers to receiving cancer genetic services. The Cancer Health Assessments Reaching Many (CHARM) study evaluated ways to increase access to genetic testing for individuals in underserved populations at risk for hereditary cancer syndromes (HCS). Here, we report the successful implementation of CHARM in a low-resource environment and the development of sustainable processes to continue genetic risk assessment in this setting. The research team involved key clinical personnel and patient advisors at Denver Health to provide input on study methods and materials. Through iterative and collaborative stakeholder engagement, the team identified barriers and developed solutions that would both facilitate participation in CHARM and be feasible to implement and sustain long term in clinical care. With a focus on infrastructure building, educational modules were developed to increase awareness among referring providers, and standard methods of identifying and managing HCS patients were implemented in the electronic medical record. Three hundred sixty-four DH patients successfully completed the risk assessment tool within the study, and we observed a sustained increase in referrals to genetics for HCS (from 179 in 2017 to 427 in 2021 post-intervention). Implementation of the CHARM study at a low-resourced safety net health system resulted in sustainable improvements in access to cancer genetic risk assessment and services that continue even after the study ended.Trial registration NCT03426878.

Epidemiology of Upper Limb Complex Regional Pain Syndrome in a Retrospective Cohort of Persons Aged 9-30 Years, 2002-2017.

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.

Accelerated curation of checkpoint inhibitor-induced colitis cases from electronic health records.

Objective: Automatically identifying patients at risk of immune checkpoint inhibitor (ICI)-induced colitis allows physicians to improve patientcare. However, predictive models require training data curated from electronic health records (EHR). Our objective is to automatically identify notes documenting ICI-colitis cases to accelerate data curation. Materials and Methods: We present a data pipeline to automatically identify ICI-colitis from EHR notes, accelerating chart review. The pipeline relies on BERT, a state-of-the-art natural language processing (NLP) model. The first stage of the pipeline segments long notes using keywords identified through a logistic classifier and applies BERT to identify ICI-colitis notes. The next stage uses a second BERT model tuned to identify false positive notes and remove notes that were likely positive for mentioning colitis as a side-effect. The final stage further accelerates curation by highlighting the colitis-relevant portions of notes. Specifically, we use BERT's attention scores to find high-density regions describing colitis. Results: The overall pipeline identified colitis notes with 84% precision and reduced the curator note review load by 75%. The segment BERT classifier had a high recall of 0.98, which is crucial to identify the low incidence (<10%) of colitis. Discussion: Curation from EHR notes is a burdensome task, especially when the curation topic is complicated. Methods described in this work are not only useful for ICI colitis but can also be adapted for other domains. Conclusion: Our extraction pipeline reduces manual note review load and makes EHR data more accessible for research.

Returning integrated genomic risk and clinical recommendations: The eMERGE study.

PURPOSE: Assessing the risk of common, complex diseases requires consideration of clinical risk factors as well as monogenic and polygenic risks, which in turn may be reflected in family history. Returning risks to individuals and providers may influence preventive care or use of prophylactic therapies for those individuals at high genetic risk. METHODS: To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores, monogenic risks, family history, and clinical risk assessments via a genome-informed risk assessment (GIRA) report and will assess uptake of care recommendations after return of results. RESULTS: GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports. The return of high-risk GIRA to individuals and providers includes guidelines for care and lifestyle recommendations. Assembling the GIRA required infrastructure and workflows for ingesting and presenting content from multiple sources. Recruitment began in February 2022. CONCLUSION: Return of a novel report for communicating monogenic, polygenic, and family history-based risk factors will inform the benefits of integrated genetic risk assessment for routine health care.

Engaging Patient Advisory Committees to Inform a Genomic Cancer Risk Study: Lessons for Future Efforts.

Introduction The Cancer Health Assessments Reaching Many study seeks to reduce disparities in genomic care. Two patient advisory committees (PACs) were formed, 1 of English speakers and 1 of Spanish speakers, to vet study processes and materials. Stakeholder engagement in research is relatively new, and we know little about how stakeholders view their engagement. We wanted to learn how patient stakeholders viewed the process, to inform future patient engagement efforts. Methods Patients at 2 study sites were invited to serve on 2 PACs. We used an iterative engagement process to solicit and incorporate patient feedback. Much of the PAC feedback on study materials and processes was incorporated. Using surveys and exit interviews, we evaluated stakeholders' experiences as PAC members. Results Nearly all PAC members felt satisfied and included in the study decisions, but surveys and exit interviews suggested the need to improve communications. Discussion Although most believed their feedback was used, and most felt included in study decisions, some said they did not know whether their opinions were used to modify materials or approaches. This suggests the need to explain to patient stakeholders the extent to which their feedback was used and to inform them about the impact that other stakeholders, such as institutional review boards, have on decisions. Conclusion Our evaluation highlights the value of dedicating resources to stakeholder engagement. Although gathering patient feedback on study materials and processes introduced time constraints and complexity to our study, adaptations to materials and processes furthered study goals.

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods.

PURPOSE: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES. METHODS: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening. RESULTS: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis. CONCLUSION: Our frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.

Lessons learned and recommendations for data coordination in collaborative research: The CSER consortium experience.

Integrating data across heterogeneous research environments is a key challenge in multi-site, collaborative research projects. While it is important to allow for natural variation in data collection protocols across research sites, it is also important to achieve interoperability between datasets in order to reap the full benefits of collaborative work. However, there are few standards to guide the data coordination process from project conception to completion. In this paper, we describe the experiences of the Clinical Sequence Evidence-Generating Research (CSER) consortium Data Coordinating Center (DCC), which coordinated harmonized survey and genomic sequencing data from seven clinical research sites from 2020 to 2022. Using input from multiple consortium working groups and from CSER leadership, we first identify 14 lessons learned from CSER in the categories of communication, harmonization, informatics, compliance, and analytics. We then distill these lessons learned into 11 recommendations for future research consortia in the areas of planning, communication, informatics, and analytics. We recommend that planning and budgeting for data coordination activities occur as early as possible during consortium conceptualization and development to minimize downstream complications. We also find that clear, reciprocal, and continuous communication between consortium stakeholders and the DCC is equally important to maintaining a secure and centralized informatics ecosystem for pooling data. Finally, we discuss the importance of actively interrogating current approaches to data governance, particularly for research studies that straddle the research-clinical divide.

Risk-reducing surgery in unaffected individuals receiving cancer genetic testing in an integrated health care system.

BACKGROUND: Germline genetic testing enables primary cancer prevention, including through prophylactic surgery. We examined risk-reducing surgeries in unaffected individuals tested for hereditary cancer susceptibly between 2010 and 2018 in the Kaiser Permanente Northwest health system. METHODS: We used an internal genetic testing database to create a cohort of individuals who received tests including one or more high-penetrance hereditary cancer susceptibility gene. We then identified, after testing, bilateral mastectomy, bilateral salpingo-oophorectomy (BSO), and total hysterectomy procedures in electronic health record and claims data through 2019. We describe surgery utilization by genetic test results and National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: The cohort included 1020 individuals, 16% with pathogenic/likely pathogenic (P/LP) variants in one or more of the following genes: BRCA1, BRCA2, CHEK2, APC, MUTYH, ATM, MSH2, PALB2, BRIP1, MLH1, MSH6, EPCAM, FLCN, RAD51C, RAD51D, or TP53. Among individuals with P/LP variants making them candidates for mastectomy, BSO, or hysterectomy per NCCN guidelines, 34% (33/97), 24% (23/94), and 8% (1/12), respectively, underwent surgery during follow-up. Fifty-three percent (18/37) of hysterectomies were among APC, BRCA1, and BRCA2 P/LP variant heterozygotes, typically concurrent with BSO. Three individuals with variants of uncertain significance (only) and 22 with negative results had prophylactic surgery after genetic testing. CONCLUSIONS: Uptake of risk-reducing surgery following usual care genetic testing appears to be lower than in studies that actively recruit high-risk patients and provide testing and follow-up care in specialized settings. Factors in addition to genetic test results and NCCN guidelines motivate prophylactic surgery use and deserve further study.

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.

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.

Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium.

PURPOSE: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, 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 the design and implementation of genomics research has yet to be realized. METHODS: The National Institutes of Health-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 used more than 1 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.