Project Summary Despite widespread recognition of pervasive patient safety problems in the U.S. health care system, research to develop feasible, scalable solutions has lagged, particularly in the ambulatory setting. The need for new approaches to improve safety is especially pressing in the care of ambulatory patients using high-risk immunosuppressive medications, as use of this category of medications has grown precipitously and reports of preventable adverse events have increased. In the last AHRQ funding period, our research team generated new epidemiological evidence of patient safety risks and adverse events and used this information to develop electronic health record-based quality measures (eMeasures) for the Centers for Medicare and Medicaid Services Quality Payment Program. In addition, we implemented these eMeasures nationally in the American College of Rheumatology's RISE registry, which includes electronic health record data from over one-third of U.S. practicing rheumatologists. In this proposal, we aim to build on this work to improve ambulatory patient safety for individuals using high-risk immunosuppressive drugs. In Aim 1, we will use data from the RISE registry linked to Medicare claims to identify emerging patient safety errors for newly approved immunosuppressive drugs and analyze these errors across race/ethnicity, socioeconomic status, medical complexity, access to care and practice characteristics. In Aim 2, we will perform a comprehensive evaluation of current national patient safety eMeasures related to immunosuppressive drugs, assessing feasibility, reliability, and validity across diverse practice settings, electronic health record systems, and visit types (telemedicine versus face-to-face). In Aim 3, we will use mixed-methods grounded in implementation science theory to determine key drivers of performance on ambulatory patient safety eMeasures. Data from this research will be used to develop and disseminate the first implementation toolkit designed to improve patient safety for high-risk immunosuppressive drugs. The proposed research will contribute significantly to the national infrastructure to improve ambulatory patient safety for the millions of Americans with immune- mediated diseases.