PROJECT SUMMARY Pharmacogenetic (PGx) testing may be particularly beneficial in patients who visit the emergency department (ED) because most presenting patients are experiencing significant problems related to their disease and/or associated medication(s). Moreover, most of the patients visiting the ED will either be admitted to the hospital or receive follow-up outpatient care in the near future. Our long-term goal is to identify patient populations where precision medicine can improve clinical outcomes and reduce healthcare costs. The overall objective of this application is to assess the feasibility, effectiveness, and economic impact of clinically implementing PGx testing, with appropriate prescribing decision support, in the ED setting. The central hypothesis is that providing such an intervention will reduce ED return visits and thus healthcare costs. The rationale for the proposed research is that PGx results, with appropriate prescribing decision support, should empower prescribers to further individualize their medication prescribing, which should decrease the rate of medication ineffectiveness and side effects. We plan to test the central hypothesis and accomplish the overall objective of this application by pursuing three specific aims. The first aim is to expand PGx-based decision support resources for clinicians in the emergency and post-emergency settings. We will accomplish this aim by expanding PGx decision support to include drug-drug-gene interactions, pharmacist medication reviews, additional gene-drug pairs, and expanding prescribing recommendations to outside the health system will increase clinical uptake of precision medicine. The second aim is to determine the feasibility and effectiveness of implementing PGx testing in high-risk patients who frequently visit the emergency department. We will accomplish this aim by completing a randomized, pragmatic clinical trial comparing high-risk ED patients receiving PGx testing to those receiving usual care. We will assess ED return rates, hospitalization rates, as well as key implementation metrics. The third aim is to quantify the cost-effectiveness and net benefit associated with implementation of PGx testing given various levels of emergency department return rate reduction. We will accomplish this aim with three analyses first estimating the cost-effectiveness of this approach and then comparing the cost-benefit using cost-per-(averted) revisit as the main outcome and comparing intervention to usual care. The proposed research is significant because it should help to identify methods to improve care while reducing costs and address multiple established barriers to PGx implementation. The proposed research is innovative because it will research an understudied, yet at-risk patient population. Ultimately, we expect to have important effectiveness, feasibility, and economic data regarding expanding precision medicine efforts in the ED setting. These results should have a positi...