PROJECT SUMMARY/ABSTRACT Half of adolescents with pediatric systemic lupus erythematosus (pSLE) do not take medications regularly as prescribed. Non-adherence increases the risk of uncontrolled disease and poor health outcomes. Non- adherence to hydroxychloroquine (HCQ), a highly effective medication recommended for nearly all patients with pSLE, is especially difficult to identify due to the poor predictive performance of available measures. To identify and ultimately reduce HCQ non-adherence in pSLE, I propose to: 1) use pharmacokinetic model simulations to define an HCQ concentration cutoff as an objective measure of non-adherence; 2) develop a novel, patient-facing digital intervention that delivers personalized feedback on HCQ concentrations to promote taking HCQ as prescribed; and 3) test feasibility and preliminary efficacy of the intervention in 25 adolescents with pSLE. Results will provide a non-adherence cutoff that will be immediately useful to identify non- adherence in clinical care. Results will also generate preliminary data to plan a larger efficacy trial designed to reduce non-adherence. The Mentored Career Development Award will provide the dedicated time, structured training, and mentorship required to advance my existing clinical pharmacology, analytic, and trial skills and develop new skills in digital interventions. My overarching career goal is to optimize therapeutics to improve health outcomes in pSLE and other pediatric rheumatic diseases using patient-centric methods. By completing the proposed research and training plans within the world-class research environment at Duke, I will acquire the skills and experience necessary to apply for independent funding and launch an academic research career dedicated to optimizing treatment and improving health outcomes in pediatric rheumatic diseases.