The eMERGE Consortium* , * The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

Background: The prevalence of familial hypercholesterolemia is 1 in 250, but <10% of patients are diagnosed. Cascade testing enables early detection of cases through systematic family tracing. Establishment of familial hypercholesterolemia cascade testing programs in the US could be informed by approaches used elsewhere. Methods: We conducted a systematic review of published studies in the English language of cascade testing for familial hypercholesterolemia, which reported the number of index cases and number of relatives tested and specified methods of contacting relatives and testing modalities methods utilized. For each study, we calculated yield (proportion of relatives who test positive) and new cases per index case, to facilitate comparison. Results: We identified 10 studies from the literature that met inclusion criteria; the mean number of probands and relatives per study was 242 and 826, respectively. The average yield was 44.76% with a range of 30% to 60.5%, and the mean new cases per index case was 1.65 with a range of 0.22 to 8.0. New cases per index case tended to be greater in studies that used direct contact versus indirect contact (2.06 versus 0.86), tested beyond first-degree relatives versus only first-degree relatives (3.65 versus 0.80), used active sample collection versus collection at clinic (4.11 versus 1.06), and utilized genetic testing versus biochemical testing (2.47 versus 0.42). Conclusions: New case detection in familial hypercholesterolemia cascade testing programs tended to be higher with direct contact of relatives, testing beyond first-degree relatives, in-home–based sample collection, and genetic testing. These findings should be helpful for establishing cascade testing programs in the United States.

Electronic health record (EHR)-based clinical decision support (CDS) can address the low awareness and undertreatment of familial hypercholesterolemia (FH), a disorder associated with a markedly increased risk of coronary heart disease. We aimed to incorporate provider perspectives into the development and implementation of a CDS tool for FH. An implementation science framework and a user-centered design process were used to create a CDS tool for FH. Primary care physicians and specialist physicians participated in qualitative interviews, usability testing and an implementation survey. The CDS was configured in two formats—a best practice alert (BPA) and an in-basket message and subsequently deployed in the EHR in silent mode. The key themes that emerged from the analysis of interview transcripts included understanding and awareness of FH, clinical workflow, physician preferences and value of CDS tools, perspectives on patient needs and values and dissemination and implementation. Recommendations related to usability included preferred CDS format and placement, content, timing and frequency, and level of alert urgency/prioritization. In response to the survey, 84.6% of physicians agreed that the CDS would improve early FH diagnosis and 92.3% agreed that it would help them identify and manage FH patients. Physician feedback led to iterative CDS refinement. In summary, we developed a CDS tool for FH using an implementation science framework and physician feedback. Initial deployment revealed a significant burden of FH and the potential for the CDS tool to have a large impact.

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Background Familial hypercholesterolemia, a prevalent genetic disorder, remains significantly underdiagnosed in the United States. Cascade testing, wherein individuals diagnosed with familial hypercholesterolemia— probands—contact their family members to inform them of their risk for familial hypercholesterolemia, has low uptake in the United States. Digital tools are needed to facilitate communication between familial hypercholesterolemia probands and their family members and to promote sharing of familial hypercholesterolemia–related risk information. Objective We aimed to create and evaluate a web-based tool designed to enhance familial communication and promote cascade testing for familial hypercholesterolemia. Methods A hybrid type 1 implementation science framework and a user-centered design process were used to develop an interactive web-based tool—FH Family Share—that enables familial hypercholesterolemia probands to communicate information about their familial hypercholesterolemia diagnosis with at-risk relatives. Probands can also use the tool to draw a family pedigree and learn more about familial hypercholesterolemia through education modules and curated knowledge resources. Usability guidelines and standards were taken into account during the design and development of the tool. The initial prototype underwent a cognitive walkthrough, which was followed by usability testing with key stakeholders including genetic counselors and patients with familial hypercholesterolemia. Participants navigated the prototype using the think-aloud technique, and their feedback was used to refine features of the tool. Results Key themes that emerged from the cognitive walkthrough were design, format, navigation, terminology, instructions, and learnability. Expert feedback from the cognitive walkthrough resulted in a rebuild of the web-based tool to align it with institutional standards. Usability testing with genetic counselors and patients with familial hypercholesterolemia provided insights on user experience, satisfaction and interface design and highlighted specific modifications that were made to refine the features of FH Family Share. Genetic counselors and patients with familial hypercholesterolemia suggested inclusion of the following features in the web-based tool: (1) a letter-to-family-member email template, (2) education modules, and (3) knowledge resources. Surveys revealed that 6 of 9 (67%) genetic counselors found information within FH Family Share very easy to find, and 5 of 9 (56%) genetic counselors found information very easy to understand; 5 of 9 (56%) patients found information very easy to find within the website, and 7 of 9 (78%) patients found information very easy to understand. All genetic counselors and patients indicated that FH Family Share was a resource worth returning to. Conclusions FH Family Share facilitates communication between probands and their relatives. Once informed, at-risk family members have the option to seek testing and treatment for familial hypercholesterolemia.