ABSTRACT/PROJECT SUMMARY There is a global emphasis and critical need to close the patient-centered outcomes research (PCOR) evidence to practice gap. Forty percent of patients do not receive evidence-based practice, 20% receive unnecessary or potentially harmful care, and sadly, the list continues. We believe interoperable clinical decision support (CDS) is an indispensable solution to help close this gap; however, poor design, lack of interoperability, and implementation barriers hinder broad adoption. At the University of Minnesota, we have extensive experience implementing and scaling user-centered CDS systems, with over 20 use cases scaled each year. Importantly, we have developed and implemented both interoperable and federally-funded CDS systems. Our healthcare system leverages a rigorous approach, SCALED (SCaling AcceptabLE cDs), to guide CDS scaling across the system. But, the current climate of each healthcare system developing “home-grown” CDS for the exact same guidelines is not tenable. Building capabilities to rapidly translate PCOR to the bedside at scale and share interoperable CDS routinely with an updated knowledge base (living evidence synthesis) is necessary. Given this, we partnered with Apervita, developers of a healthcare technology platform for digital quality measurement and decision support, to develop an interoperable clinical practice guideline leveraging CPG-on-FHIR (Fast Healthcare Interoperability Resources) to prevent inpatient COVID-19 venous thromboembolism (VTE). The proposed R18 project will adapt a currently deployed CDS system to also deliver a VTE prevention guideline for adult patients with traumatic brain injury (TBI). We believe this is an ideal PCOR use case given PCORI’s continued effort to combat VTE in trauma and our experience previously implementing this guideline. Our overall goal is to successfully scale, evaluate, and maintain an interoperable TBI CDS across our 4-institution collaborative network. For Aim 1, we will conduct a Hybrid Type 2 randomized stepped wedge effectiveness- implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using RE-AIM. Despite best efforts, it highly likely CDS adoption will vary across each site; Aim 2 will allow us to understand why. In Aim 2, we will evaluate implementation processes across trial sites guided by the EPIS implementation framework (determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date an accepted process for evidence maintenance does not exist. In Aim 3, we will pilot a “Living Guideline” process model for the VTE prevention CDS systems. Ultimately, this project will scale CDS across a diverse collaborative CDS community serving as an important demonstration of this critical healthcare challenge. We will integrate lessons learned for a planned national scaling in collaboration with engagement of U.S. trauma societies. Imp...