PROJECT SUMMARY This application addresses the RFA-CE-18-006: Research Grants for the Primary or Secondary Prevention of Opioid Overdose (R01). Opioid overdoses have reached alarming numbers in the United States. This is in part due to increases in opioid prescriptions for acute and chronic pain, leading to a rise in opioid use disorders and overdose of these drugs. Given that the path to addiction begins with a prescription for many patients, acute care, emergency departments, and inpatient admissions should be a key area of focus for primary and secondary prevention of opioid dependence and overdose. Identifying “at risk” patients prior to initiating or escalating opioid treatment and intervening on risk factors that are either modifiable or actionable on the part of physicians or other healthcare providers are important steps in reducing prescription medication use disorder. The goal of the proposed development and pilot study, “Implementing a Multimodal Path to RecOVEry (IMPROVE),” is to utilize PRIMUM, our healthcare system’s existing clinical decision support platform, to develop and implement a comprehensive strategy for enhanced identification of, and intervention on, modifiable and/or actionable risk factors for primary and secondary prevention of opioid misuse, abuse, and overdose during presentation for acute care and post-discharge while appropriately managing pain and optimizing patient safety. The specific aims are to: 1. Develop and pilot test primary prevention strategies in acute care (inpatient and emergency department) to reduce development of opioid dependence and incidence of overdose by integrating clinical decision support to reduce the number, dose, and duration of opioid prescriptions, to reduce reliance on opioid monotherapy, and to provide a pathway for intervening on modifiable risk factors. 2. Develop and pilot test secondary prevention strategies in acute care to identify patients at moderate to high risk of opioid overdose and to provide direction for intervention to include acute and post-discharge support. 3. To utilize lessons learned during the pilot test to establish a strategy for sustainability, dissemination within the System, and translation to other health systems, including documentation of cost and resources required. The proposed research will provide evidence that comprehensive clinical decision support and targeted interventions will lead to a reduction in the incidence of opioid overdose, increase proportion of patients receiving multimodal pain management, and increase prescribing behaviors in compliance with CDC Guideline upon discharge from acute care settings. This contribution will be highly significant because it will reduce unintentional drug overdoses and ultimately provide a model that can be implemented into other communities.