Development and validation of a patient-reported outcome measure to improve quality of life related to cutaneous chronic GVHD - PROJECT SUMMARY Candidate: I am an Assistant Professor of Dermatology and Medicine at the University of Pennsylvania and a physician-scientist with a Master of Science in Clinical Epidemiology as well as expertise caring for patients with GVHD. I have a strong track record of published research at the intersection of dermatology, cancer, and transplantation. With the support of this career development award, I plan to further develop my scientific career in two ways. First, I have been struck by the substantial health-related quality of life (HrQOL) impact that results from skin chronic GVHD (cGVHD). I plan to gain expertise in the science of measuring disease burden and the approaches used to conduct studies that improve patient-centered outcomes. Second, I will move from analysis of existing datasets towards the design and execution of prospective observational and interventional studies that improve HrQOL, morbidity, and mortality for patients with skin cGVHD. Background: Skin cGVHD is a major contributor to morbidity, mortality, and impaired HrQOL after allogeneic hematopoietic cell transplantation. However, patient-reported outcome measures (PROs) are not routinely used to develop, evaluate, or select treatments. PROs provide complementary information to clinician-reported measures, can predict clinical outcomes including survival, and are required by the FDA to support labeling claims of new therapies. The absence of a valid and reliable PRO for skin cGVHD presents a critical barrier to designing and executing prospective studies. Without such a measure, we cannot determine whether interventions improve the outcomes that are important to patients. Training: To achieve research independence, I require additional training in 1) mixed methods research and consensus formation; 2) psychometric methods; and 3) design, implementation, and analysis of prospective observational studies and clinical trials that incorporate patient- centered outcomes. Mentors: My training and research will be overseen by Dr. Joel Gelfand, who has extensive experience mentoring K23 awardees to successful independent research careers, and expertise in instrument development, patient-centered research, and prospective observational and interventional studies in chronic inflammatory skin disease. Dr. Stephanie Lee (PRO development, prospective observational studies and clinical trials in GVHD), and Dr. Marilyn Schapira (psychometric methods, patient-centered outcomes) will be additional co-mentors. Dr. Alison Loren (GVHD at UPenn), Dr. Eric Tkaczyk (multicenter studies in skin cGVHD) and Dr. Daniel Shin (biostatistics) will be advisors. Research: To achieve my objective of developing and validating a PRO for skin cGVHD, I will pursue 3 aims: 1) Generate and evaluate content validity of an item bank for a skin cGVHD PRO; 2) Develop a skin cGVHD PRO scale using state-of-the-art psychometric methods; and 3) Evaluate responsiveness of the skin cGVHD PRO to therapy in a single-center prospective cohort study. I will use the findings from this K23 as the basis for future research including an R01 or U01 proposal to conduct a clinical trial with the skin cGVHD PRO as a clinical endpoint.
