Benefits, harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model.

PURPOSE: Population newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain. METHODS: We developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns. Those identified with pathogenic/likely pathogenic variants associated with increased risk of HCM underwent surveillance and recommended treatment, whereas in usual care, individuals with family histories of HCM underwent surveillance. RESULTS: In a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 years by 44 (95% uncertainty interval [UI] = 10-103) however increase the numbers of children undergoing surveillance by 8127 (95% UI = 6308-9664). Compared with usual care, newborn genetic screening costs $267,000 per life year saved (95% UI, $106,000 to $919,000 per life year saved). CONCLUSION: Newborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance. This study shows how modeling can provide insights into the tradeoffs between benefits and costs that will need to be considered as newborn genetic screening is more widely adopted.

Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Community Health Study/Study of Latinos.

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.

Improved provider preparedness through an 8-part genetics and genomic education program.

PURPOSE: Large-scale genetics education appropriate for general practice providers is a growing priority. We describe the content and impact of a mandatory system-wide program implemented at Sanford Health. METHODS: The Imagenetics Initiative at Sanford Health developed a 2-year genetics education program with quarterly web-based modules that were mandatory for all physicians and advanced practice providers. Scores of 0 to 5 were calculated for each module on the basis of the number of objectives that the participants reported as fulfilled. In addition, the participants completed surveys before starting and after finishing the education program, which included a 7-item measure scored 7 to 28 on the perceived preparedness to practice genetics. RESULTS: Between 2252 and 2822 Sanford Health employees completed each of the 8 quarterly education modules. The ratings were highest for the module about using genomics to improve patient management (mean score = 4.3) and lowest for the module about different types of genetic tests and specialists. The mean perceived preparedness scores increased from 15.7 at pre-education to 19.1 at post-education (P < .001). CONCLUSION: Web-based genetics education was highly effective in increasing health care providers' confidence about using genetics. Both comfort with personal knowledge and confidence regarding access to the system's genomic medicine experts increased significantly. The results demonstrate how scalable approaches can improve provider preparedness.

Primary care providers' responses to unsolicited Lynch syndrome secondary findings of varying clinical significance.

PURPOSE: How primary care providers (PCPs) respond to genomic secondary findings (SFs) of varying clinical significance (pathogenic, uncertain significance [VUS], or benign) is unknown. METHODS: We randomized 148 American Academy of Family Physicians members to review three reports with varying significance for Lynch syndrome. Participants provided open-ended responses about the follow-up they would address and organized the SF reports and five other topics in the order they would prioritize responding to them (1 = highest priority, 6 = lowest priority). RESULTS: PCPs suggested referrals more often for pathogenic variants or VUS than benign variants (72% vs. 16%, p < 0.001). PCPs were also more likely to address further workup, like a colonoscopy or esophagogastroduodenoscopy, in response to pathogenic variants or VUS than benign variants (43% vs. 4%, p < 0.001). The likelihoods of addressing referrals or further workup were similar when PCPs reviewed pathogenic variants and VUS (both p > 0.46). SF reports were prioritized highest for pathogenic variants (2.7 for pathogenic variants, 3.6 for VUS, 4.3 for benign variants, all p ≤ 0.014). CONCLUSION: Results suggest that while PCPs appreciated the differences in clinical significance, disclosure of VUS as SFs would substantially increase downstream health-care utilization.

Precision Population Medicine in Primary Care: The Sanford Chip Experience.

Genetic testing has the potential to revolutionize primary care, but few health systems have developed the infrastructure to support precision population medicine applications or attempted to evaluate its impact on patient and provider outcomes. In 2018, Sanford Health, the nation's largest rural nonprofit health care system, began offering genetic testing to its primary care patients. To date, more than 11,000 patients have participated in the Sanford Chip Program, over 90% of whom have been identified with at least one informative pharmacogenomic variant, and about 1.5% of whom have been identified with a medically actionable predisposition for disease. This manuscript describes the rationale for offering the Sanford Chip, the programs and infrastructure implemented to support it, and evolving plans for research to evaluate its real-world impact.