Candidate: April Jorge, MD is an Instructor in Medicine at Harvard Medical School (HMS) and an Assistant in Medicine in the Rheumatology Unit at Massachusetts General Hospital (MGH). After graduating from the University of Maryland magna cum laude, she received her MD from Georgetown University, and she completed her internal medicine residency at Northwestern University. She completed her rheumatology fellowship at MGH, during which she also completed the Harvard Catalyst Clinical and Translational Research Academy and began working with Hyon Choi, MD, DrPH. Dr. Jorge's prior work has resulted in 15 peer- reviewed original papers, with 13 as the first author or co-first author. Her goal is to become an independent investigator and innovative leader in patient-oriented research of systemic lupus erythematosus (SLE). Mentorship, Training Activities, and Environment: Dr. Jorge will conduct the proposed project at MGH under the mentorship of Hyon Choi, MD, DrPH and co-mentorship of Karen Costenbader, MD, MPH and Karen Sepucha, PhD. Dr. Choi is a world-renowned, NIH-funded physician scientist in advanced clinical epidemiology of rheumatic conditions, ranging from common disorders to rare but serious disorders (e.g., SLE). He has served as a mentor for several prior K awardees. Dr. Costenbader is a clinical investigator and expert in SLE who is also an experienced mentor of K awardees. Dr. Sepucha is a leading expert in patient-centered decision science. Dr. Jorge's research will also benefit from the specific expertise of her key collaborators, including advanced clinical epidemiology methods, machine learning prediction algorithms, and decision- analytic modeling. In addition to receiving excellent mentorship, she will acquire new skills through didactics in advanced clinical epidemiology and pharmacoepidemiology, risk prediction, eliciting patient preferences with a mixed methods research approach, and decision-analytic modeling. Research: SLE carries increased risks of multiple comorbidities and double the risk of death compared to the general population. Current treatment is limited in part by few proven medications and adverse treatment effects. The central goal of this research is to improve long-term SLE outcomes by integrating personalized risks of potential harms and benefits with patient preferences to guide the personalized, patient-centered use of key lupus medications. To achieve this goal, she will risk stratify patients for potential harms of treatment, i.e., hydroxychloroquine retinopathy and infection with belimumab use versus other immunosuppressants, and other adverse outcomes, i.e., severe COVID-19 infection (Aim 1). She will elicit patient preferences for SLE treatment through a discrete choice experiment (Aim 2a) and will integrate patient preferences with personalized risks through a multi-criteria decision analysis to determine the optimal hydroxychloroquine dose in SLE care (Aim 2b). Completion of this proposal and training plan will position Dr. Jorge with the vital experience to become an independent clinical investigator in patient-oriented research of SLE.

Project Narrative Systemic lupus erythematosus (SLE) is a heterogeneous systemic condition associated with serious morbidity and premature mortality, yet treatment options are limited. There is uncertainty regarding the optimal use of the two FDA-approved lupus medications, hydroxychloroquine and belimumab, due in part to the risks of adverse treatment effects including hydroxychloroquine retinopathy and infection. This Career Development Award focuses on applying advanced clinical epidemiology and patient-centered decision science to integrate personalized risks of potential harms and benefits with patient preferences to guide the personalized, patient- centered use of key lupus medications, including specifically the optimal dose of hydroxychloroquine in SLE care.