PROJECT SUMMARY Adverse drug events (ADE) are frequent in ambulatory care, leading to an estimated 4.5 million patient visits in ambulatory care each year, and a substantial proportion of ADEs are preventable. Failure to communicate medication discontinuations to patients’ pharmacies is a major contributing factor to these errors; an estimated 1.5 – 3% of prescriptions are dispensed in error following discontinuation by a clinician. With over 1.7 billion e-prescriptions in 2017, this poses a major medication safety concern. The National Council for Prescription Drug Programs’ SCRIPT standard (version 10.6) supports the functionality to send electronic prescriptions cancellations from electronic health records (EHRs) to pharmacies, known as CancelRx. However, adoption of CancelRx has been limited, and its impact on patient outcomes and the workflows of key stakeholders remains largely unknown. A growing literature recognizes the importance of shared technology to support patient engagement and improve clinical outcomes and identifies the limitations of existing technology and communication tools used in outpatient settings. The specific aims of this study are to: Develop strategies to optimize CancelRx implementation to support patients in medication management and identify where further health IT development is needed Measure the impact of CancelRx on patient outcomes, including dispensing errors and documented ADE following medication discontinuation We will evaluate the impact of electronic prescription cancellation in ambulatory care settings with diverse patients with serious medical conditions and high risk medication use. We will use qualitative and human factors methods and the lens of the patient work system model to identify patient needs and remaining gaps in communication and care coordination following CancelRx implementation. We will then engage clinical and industry stakeholders in the process of human centered design to prototype solutions which can be implemented locally and shared with other organizations. Finally, we will use EHR and pharmacy data to identify dispense-after-discontinuation medication errors and ADE and conduct an interrupted time series analysis to determine the impact of CancelRx implementation on these outcomes. Key anticipated scientific contributions of this research include an understanding of the impact of CancelRx on patient medication management processes and outcomes, including dispensing errors, development of strategies to improve CancelRx implementation that could be disseminated to other health care settings, engagement of industry leaders in the identification of desirable health IT features, and validation of a measurement strategy for CancelRx evaluation in other settings and with community partners.