PROJECT SUMMARY/ABSTRACT Opioid misuse is an epidemic and a public health crisis. At least 2 million people have an opioid use disorder (OUD) involving prescription opioids, and 600,000 have heroin OUD6. Alarmingly, 80% of heroin users used prescription opioids before transitioning to heroin7. It is therefore critical to ensure that opioid pain therapies are administered safely, in a way that minimizes the potential for aberrant drug related behaviors. This necessitates individualized opioid regimens and strict adherence, enabling effective pain control without producing euphoria or withdrawals, both of which can lead to drug seeking behaviors. Continuous Precision Medicine (CPM) aims to develop a software ecosystem to reduce opioid misuse and over-prescription in postoperative patients. In a self-funded Phase I, we have developed clinical decision support software, which consists of a server for data management and analytics and a mobile client application for the patient. The digital platform delivers a personalized schedule, records dosing and pain levels, and motivates adherence to dosing by scoring compliance. In this project, we propose to evaluate and improve the CPM suite of clinical decision support tools and provide clinicians and patients with immediately actionable information to decrease over-prescription and misuse of opioids during the post-operative period. In the proposed Phase II SBIR project, CPM will refine and evaluate the mobile application, deploy and test a Prescriber Portal with dashboard functions to enable physicians to overlay pharmacokinetic and pharmacodynamic modeling to improve prescribing practices and deter drug-habit-forming behavior, and prepare materials for a 501(k) application submission. The CPM app, patient data, and provider portal, taken together and optimally employed to improve patient-provider communication and treatment planning, has the potential to prevent negative sequelae associated with over-prescription and misuse of opioids, including opioid use disorder, overdose, and death.