Lessons Learned from the Pilot Phase of a Population-Wide Genomic Screening Program: Building the Base to Reach a Diverse Cohort of 100,000 Participants.

Background and Objectives: Genomic information is increasingly relevant for disease prevention and risk management at the individual and population levels. Screening healthy adults for Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia using a population-based approach can help identify the 1−2% of the US population at increased risk of developing diseases associated with these conditions and tailor prevention strategies. Our objective is to report findings from an implementation science study that evaluates multi-level facilitators and barriers to implementation of the In Our DNA SC population-wide genomic screening initiative. Methods: We established an IMPACTeam (IMPlementAtion sCience for In Our DNA SC Team) to evaluate the pilot phase using principles of implementation science. We used a parallel convergent mixed methods approach to assess the Reach, Implementation, and Effectiveness outcomes from the RE-AIM implementation science framework during the pilot phase of In Our DNA SC. Quantitative assessment included the examination of frequencies and response rates across demographic categories using chi-square tests. Qualitative data were audio-recorded and transcribed, with codes developed by the study team based on the semi-structured interview guide. Results: The pilot phase (8 November 2021, to 7 March 2022) included recruitment from ten clinics throughout South Carolina. Reach indicators included enrollment rate and representativeness. A total of 23,269 potential participants were contacted via Epic's MyChart patient portal with 1976 (8.49%) enrolled. Black individuals were the least likely to view the program invitation (28.9%) and take study-related action. As a result, there were significantly higher enrollment rates among White (10.5%) participants than Asian (8.71%) and Black (3.46%) individuals (p < 0.0001). Common concerns limiting reach and participation included privacy and security of results and the impact participation would have on health or life insurance. Facilitators included family or personal history of a Tier 1 condition, prior involvement in genetic testing, self-interest, and altruism. Assessment of implementation (i.e., adherence to protocols/fidelity to protocols) included sample collection rate (n = 1104, 55.9%) and proportion of samples needing recollection (n = 19, 1.7%). There were no significant differences in sample collection based on demographic characteristics. Implementation facilitators included efficient collection processes and enthusiastic clinical staff. Finally, we assessed the effectiveness of the program, finding low dropout rates (n = 7, 0.35%), the identification of eight individuals with Tier 1 conditions (0.72% positive), and high rates of follow-up genetic counseling (87.5% completion). Conclusion: Overall, Asian and Black individuals were less engaged, with few taking any study-related actions. Strategies to identify barriers and promoters for the engagement of diverse populations are needed to support participation. Once enrolled, individuals had high rates of completing the study and follow-up engagement with genetic counselors. Findings from the pilot phase of In Our DNA SC offer opportunities for improvement as we expand the program and can provide guidance to organizations seeking to begin efforts to integrate population-wide genomic screening.

A pragmatic implementation research study for In Our DNA SC: a protocol to identify multi-level factors that support the implementation of a population-wide genomic screening initiative in diverse populations.

BACKGROUND: In 2021, the Medical University of South Carolina (MUSC) partnered with Helix, a population genetic testing company, to offer population-wide genomic screening for Centers for Disease Control and Preventions' Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia to 100,000 individuals in South Carolina. We developed an implementation science protocol to study the multi-level factors that influence the successful implementation of the In Our DNA SC initiative. METHODS: We will use a convergent parallel mixed-methods study design to evaluate the implementation of planned strategies and associated outcomes for In Our DNA SC. Aims focus on monitoring participation to ensure engagement of diverse populations, assessing contextual factors that influence implementation in community and clinical settings, describing the implementation team's facilitators and barriers, and tracking program adaptations. We report details about each data collection tool and analyses planned, including surveys, interview guides, and tracking logs to capture and code work group meetings, adaptations, and technical assistance needs. DISCUSSION: The goal of In Our DNA SC is to provide population-level screening for actionable genetic conditions and to foster ongoing translational research. The use of implementation science can help better understand how to support the success of In Our DNA SC, identify barriers and facilitators to program implementation, and can ensure the sustainability of population-level genetic testing. The model-based components of our implementation science protocol can support the identification of best practices to streamline the expansion of similar population genomics programs at other institutions.

Positive predictive value highlights four novel candidates for actionable genetic screening from analysis of 220,000 clinicogenomic records.

PURPOSE: To identify conditions that are candidates for population genetic screening based on population prevalence, penetrance of rare variants, and actionability. METHODS: We analyzed exome and medical record data from >220,000 participants across two large population health cohorts with different demographics. We performed a gene-based collapsing analysis of rare variants to identify genes significantly associated with disease status. RESULTS: We identify 74 statistically significant gene-disease associations across 27 genes. Seven of these conditions have a positive predictive value (PPV) of at least 30% in both cohorts. Three are already used in population screening programs (BRCA1, BRCA2, LDLR), and we also identify four new candidates for population screening: GCK with diabetes mellitus, HBB with ß-thalassemia minor and intermedia, PKD1 with cystic kidney disease, and MIP with cataracts. Importantly, the associations are actionable in that early genetic screening of each of these conditions is expected to improve outcomes. CONCLUSION: We identify seven genetic conditions where rare variation appears appropriate to assess in population screening, four of which are not yet used in screening programs. The addition of GCK, HBB, PKD1, and MIP rare variants into genetic screening programs would reach an additional 0.21% of participants with actionable disease risk, depending on the population.

Toward clinical genomics in everyday medicine: perspectives and recommendations.

Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of illness in our society, it is of interest to ask how clinical genome and exome sequencing can be constructively integrated more broadly into the routine practice of medicine for the betterment of public health. In November 2014, 46 experts from academia, industry, policy and patient advocacy gathered in a conference sponsored by Illumina, Inc. to discuss this question, share viewpoints and propose recommendations. This perspective summarizes that work and identifies some of the obstacles and opportunities that must be considered in translating advances in genomics more widely into the practice of medicine.