A0680
Title: Identifying new clinical trial surrogate endpoints in rare diseases: The PARASOL approach
Authors: Abigail Smith - Northwestern University (United States) [presenting]
Margaret Helmuth - University of Michigan (United States)
Laura Mariani - University of Michigan (United States)
Abstract: Reasonably likely surrogate endpoints in rare diseases are challenging to develop due to a lack of data to provide regulatory confidence in the prediction of clinical benefit. In focal segmental glomerulosclerosis (FSGS), a rare glomerular disease affecting children and adults, endpoints are needed to support the development of new therapies. Proteinuria and GFR as clinical trial endpoints in focal segmental glomerulosclerosis (PARASOL) is an international collaborative effort to integrate observational, registry, and clinical trial data to define relationships between short-term changes in key disease activity and long-term clinical outcomes. Twenty-two datasets from around the world have been identified for data sharing. Challenges in integrating datasets include variation in the measurement of key biomarkers and the precision of documentation of a diagnosis of FSGS. This variation compounds underlying disease heterogeneity in age, underlying etiology, and rate of progression. Once combined, survival analysis approaches, including time-dependent and landmarked models, are applied to assess the ability of eGFR and UPCR to predict kidney failure in subgroups of patients with FSGS. In addition, clinical and data-driven approaches are used to define potential endpoints for trials, and sample size needs are assessed. Results from this project inform feasible clinical trial design and regulatory pathways for developing new therapies for FSGS.
