Clinical genomic population health testing for 431 genes implemented through family medicine practices: the Vermont experience

ABSTRACT

Integration of genomics into health practice depends on successful implementation in non-research settings. We describe a medical home-centered implementation at the intersection of genomic medicine and population health in the UVM Health Network. In this clinical implementation, the hospital laboratory orchestrates a collaboration involving primary care providers (PCPs), patient and family advisors, health system administrators, clinical genetics services, oncologists and cardiologists, Vermont’s accountable care organization, and a commercial CLIA genomic testing laboratory. Phenotypically unselected adult primary care patients are offered “The Genomic DNATest” at no cost as part of their regular care. Testing is introduced by primary care providers and their staff using a brief animated video and printed decision aids with graded detail. Question resolution and pre- and post-test genetic counseling is offered at no cost using telephone, video, or in-person visits, and is coordinated bya single phone and email contact point, the Genomic Medicine Resource Center. 431 genes are sequenced for germline health risk and recessive carrier variants;only pathogenic and likely-pathogenic variants are reported. New reports are issued when reported and unreported variants are later reclassified. Test reports are reviewed by a clinical geneticist and genetic counselor. Two brief "action plans" are developed with PCP and patient focus in a single messaging document. This is prepended to the lab reports before release to the PCP, who reviews and then conveys them to the patient. PCPs and their staff receive initial training on the test and process and are invited to participate in an online community with monthly video case discussions. Among the first 72 patients tested, 17% had a health risk identified. This included dominantly inherited disorders and bi-allelic or hemizygous variants for common recessive disorders. Care pathways created in advance using multi-disciplinary expertise were activated for those. Free testing for blood relatives was made available. 76% of tested patients had at least one heterozygous recessive disease variant identified, and low-cost partner testingwas made available. Frequency of positive test results was in line with population frequency predictions. Pre- and post-test genetic counseling uptakewas lower than expected. This raised the question of unmet informational needs. A 2-page anonymous process quality survey mailed twice to the first 61 tested patients had a 31% return rate. Key findings included (1) pre-test engagement methods and decision aids were helpful;(2) the testing decision was influenced equally by value for the individual’s health, for their family’s health, and for researchers;(3) emotions during the ∼4-week time to results were neutral or excited, with none experiencing anxious feelings, and none reported the wait time as too long;(4) 21% reported contacting the Genomic Medicine Resource Center;(5) 16% reported referral to a specialist due to their result;(6) about half reported sharing the results with family members, but none reported any family members getting tested;(7) none indicated they were dissatisfied with the testing and result process, and only one responded they would not recommend others get the test;and (8) all agreed or somewhat agreed that the PCPs officewas the right place to do this testing.While this implementation was designed with scalability and a low management profile in mind, several systems-level barriers were encountered that contributed to lower engagement efforts and slower expansion than planned. This included lack of institutional information technology resources to surmount paper-based systems for requisitions, sample-routing, and consent forms;dependency of the patient engagement process during PCP visits on rooming and nursing staff during times of staffing shortages;susceptibility to practice model disruptions and priorities caused by the Covid-19 pandemic;and PCP time distraction resulting from user interface and polic changes in our EHR during the pilot. These barriers are targets for study and continuous process improvement activities. In summary, an example of clinical genomic population health testing using a medical-home focus has been successfully implemented in a non-research setting, supported by multi-disciplinary collaboration. This implementation depends on minimal staff, avoids financial barriers to access and genetic counseling, and offers a short, defined, test turnaround time as compared to similar biobank-based research programs. Tested patients find the program satisfactory, and meaningful test results are at least as common as in existing population health risk screening archetypes.