Project Summary Using genomic variation to tailor therapeutic, preventative, and diagnostic decision-making is a potentially transformative approach to clinical care. However, uncertainty about clinical impact and economic value presents a critical barrier to broad adoption. The Integrated, Individualized, Intelligent Prescribing (I3P) Clinical Trials Network includes three clinically and sociodemographically diverse health systems to IGNITE 2: Metro General Hospital at Meharry Medical College, Sanford Health and Vanderbilt University Medical Center (VUMC). The Network will develop infrastructure to quickly recruit large, diverse patient populations, return results at the time of clinical indication, and provide health care providers with understandable, implementable guidance during the course of the trial. The first aim will develop and implement infrastructure to efficiently conduct pragmatic clinical trials involving Genomic Medicine across the diverse settings within I3P. The second aim proposes a randomized, pragmatic clinical trial of multiplexed pharmacogenomics testing across the IGNITE 2 Network to establish the clinical utility of panel testing. And finally, I3P will develop and implement an IGNITE 2 Network-wide capability to calculate Phenotype Risk Scores across health system populations to efficiently identify and intervene on patients likely to have a genomic diagnosis. All of the institutions within the I3P Network will leverage their strong record of collaboration within IGNITE 1 and other NIH funded consortia to accomplish these aims.