Abstract The National Human Genome Research Institute’s 2020 strategic vision charts a path toward an audacious goal – that in 10 years genomic medicine will simply be medicine. Today, though, genomic medicine is neither routine nor equitably distributed. Contributing factors include lack of structured genomic data in the electronic health record (EHR) to facilitate point-of-care decision support, limited portability of genomic data across health systems, and inadequate access to genomic medicine expertise in rural and other underserved communities. We propose to address these challenges as a Clinical Site in the Genomic-Enabled Learning Health System (gLHS) Network. We will use implementation science methods and learning health system (LHS) principles to generate genomic medicine resources that can be implemented effectively across diverse healthcare settings. Geisinger is an established LHS and recognized leader in genomics, with the world’s largest biobank-based genomic screening program. Geisinger provides care in all medical specialties across the lifespan to a largely rural, socioeconomically diverse patient population. Our LHS is enabled by a robust research, innovation and data infrastructure. Further, our investigator team includes national leaders in genomic medicine, experts in genomic and clinical data science, implementation science, health communication, and decision science, and representatives from community health systems that differ from Geisinger in key characteristics. In Year 1 of the gLHS Network we will collaborate with the Network to identify genomic medicine interventions that aim to have significant population health impact: 1) genomic screening in primary care for clinically actionable disease risk; 2) EHR-integrated implementation of PGx for patients age 50+ on multiple medications; and 3) EHR- integrated clinician- and patient-facing clinical decision support for managing hereditary cancer risk. In Years 2- 4 we will implement and evaluate the genomic medicine interventions selected by the Network. We will use the Conceptual Model of Implementation Research (CMIR) to inform outcomes to assess across the interventions. Grounding this cycle of implementation and evaluation in the CMIR will allow us to take the same theoretical approach regardless of which interventions the Network selects. And it will allow identification of core implementation elements and documentation of institution-specific adaptations to standardize outcomes and lower barriers to implementation of resources in other health systems. In the final grant year, we will use Implementation Mapping and a sustainability framework to inform design of qualitative interviews with key operational and strategic leaders in our community partners’ health systems. We will then adapt the Network- selected resources and implementation strategies according to findings from the qualitative interviews, using implementation science frameworks to document adaptations to resources and strategies. Through the gLHS Network, we expect to produce resources and strategies for implementation that will substantially advance NHGRI’s audacious goal of routine, equitable genomic medicine.

NARRATIVE Genomic medicine has long been recognized as having the potential to improve population health, but it has not become routine, equitably distributed healthcare. Rigorous evaluations of how genomic medicine interventions are implemented across diverse healthcare settings are necessary to realize the population health potential of genomic medicine. We propose to contribute our expertise in genomic medicine, implementation science and learning health systems as a Clinical Site in the Network of Genomics-Enabled Learning Health Systems, advancing the goal of improving population health by making genomic medicine routine across all healthcare settings.