The VA Genomics Learning Health System: Implementing genomic medicine across diverse veteran communities - PROJECT SUMMARY The Veterans Health Administration of the Department of Veterans Affairs (VA) is the largest and most diverse learning health system (LHS) in the US, caring for more than 9 million patients annually in every state and US territory. A full quarter of VA healthcare enrollees nationally live in HRSA-designated Health Professional Shortage Areas (HPSAs). VA patients also have a greater burden of physical and mental health comorbidities than the general US population. Nonetheless, a focus on performance measurement and improvement has kept the quality of VA care as high or higher than in the private sector. This quality has been achieved by VA’s innovation in implementation science and embodiment of LHS attributes, leveraging its vast clinical electronic health record (EHR) data, robust informatics infrastructure, and patient-centered focus to continually evaluate and improve patient care based on real-time monitoring and feedback. The VA is also a national leader in clinical genomic medicine, including telegenetics, pharmacogenomics, and precision oncology. VA innovations in genomic medicine have been driven by its LHS ecosystem of data-informed continuous quality improvement (CQI), innovation, and national dissemination of implementation strategies found to be effective at local and regional levels. In this project, VA will bring its national LHS infrastructure and genomic medicine implementation strategies to a network of other genomics-enabled LHS. The network will conduct implementation projects centered on a mainstream model for delivery of genomic medicine that promotes the use of evidence-based, guideline-concordant genetic testing by frontline clinicians. The VA genomics-enabled LHS will contribute to this network effort by 1) identifying and sharing with the network an implementation approach and strategies with high potential for implementation across diverse healthcare systems, including under-resourced settings; 2) proposing three implementation trials for network-wide conduct (pharmacogenomic testing to optimize pharmacotherapy, germline testing to inform cancer treatment, and EHR identification and germline testing to diagnose unrecognized monogenic disease); and 3) working with the network to conduct implementation projects of genomic medicine interventions across a spectrum of clinical conditions and patient characteristics within the VA genomics-enabled LHS and its community, recruiting underserved populations and geographic areas. Through participation in this network, the VA will disseminate its deep LHS expertise to other clinical sites and in turn bring the learnings from the larger network to improve the genomic health care and outcomes of the nation’s military veterans, their families, and communities.