RESUMEN
The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery.
Asunto(s)
Prestación Integrada de Atención de Salud , Enfermedad/genética , Registros Electrónicos de Salud , Exoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Adulto , Diseño de Fármacos , Frecuencia de los Genes , Genómica , Humanos , Hipolipemiantes/farmacología , Mutación INDEL , Lípidos/sangre , Terapia Molecular Dirigida , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
PURPOSE: Geisinger Health System (GHS) provides an ideal platform for Precision Medicine. Key elements are the integrated health system, stable patient population, and electronic health record (EHR) infrastructure. In 2007, Geisinger launched MyCode, a system-wide biobanking program to link samples and EHR data for broad research use. METHODS: Patient-centered input into MyCode was obtained using participant focus groups. Participation in MyCode is based on opt-in informed consent and allows recontact, which facilitates collection of data not in the EHR and, since 2013, the return of clinically actionable results to participants. MyCode leverages Geisinger's technology and clinical infrastructure for participant tracking and sample collection. RESULTS: MyCode has a consent rate of >85%, with more than 90,000 participants currently and with ongoing enrollment of ~4,000 per month. MyCode samples have been used to generate molecular data, including high-density genotype and exome sequence data. Genotype and EHR-derived phenotype data replicate previously reported genetic associations. CONCLUSION: The MyCode project has created resources that enable a new model for translational research that is faster, more flexible, and more cost-effective than traditional clinical research approaches. The new model is scalable and will increase in value as these resources grow and are adopted across multiple research platforms.Genet Med 18 9, 906-913.
Asunto(s)
Bancos de Muestras Biológicas , Investigación Biomédica , Registros Electrónicos de Salud , Medicina de Precisión , Genotipo , Humanos , Fenotipo , Salud PúblicaRESUMEN
INTRODUCTION: The Learning Health Care System (LHCS) model seeks to utilize sophisticated technologies and competencies to integrate clinical operations, research and patient participation in order to continuously generate knowledge, improve care, and deliver value. Transitioning from concept to practical application of an LHCS presents many challenges but can yield opportunities for continuous improvement. There is limited literature and practical experience available in operationalizing the LHCS in the context of an integrated health system. At Geisinger Health System (GHS) a multi-stakeholder group is undertaking to enhance organizational learning and develop a plan for operationalizing the LHCS system-wide. We present a framework for operationalizing continuous learning across an integrated delivery system and lessons learned through the ongoing planning process. FRAMEWORK: The framework focuses attention on nine key LHCS operational components: Data and Analytics; People and Partnerships; Patient and Family Engagement; Ethics and Oversight; Evaluation and Methodology; Funding; Organization; Prioritization; and Deliverables. Definitions, key elements and examples for each are presented. The framework is purposefully broad for application across different organizational contexts. CONCLUSION: A realistic assessment of the culture, resources and capabilities of the organization related to learning is critical to defining the scope of operationalization. Engaging patients in clinical care and discovery, including quality improvement and comparative effectiveness research, requires a defensible ethical framework that undergirds a system of strong but flexible oversight. Leadership support is imperative for advancement of the LHCS model. Findings from our ongoing work within the proposed framework may inform other organizations considering a transition to an LHCS.