Abstract: INFO09-SA
Findable, Accessible, Interoperable, Reusable (FAIR) Access to Reusable Novel Biomarker Study Electronic Case Report Forms with Metadata Annotation and Statistical Analysis Plan Template for Biomarker Qualification
Session Information
- Informational Posters - 3
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- No subcategory defined
Authors
- Friedman, Gary Steven, Critical Path Institute, Tucson, Arizona, United States
- King, Nicholas M., Critical Path Institute, Tucson, Arizona, United States
- Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Hoffmann, Steven C., Foundation for the National Institutes of Health, North Bethesda, Maryland, United States
- Murray, Patrick T., University College Dublin, Dublin, Ireland
- Peron, Katrina Jolene, Critical Path Institute, Tucson, Arizona, United States
- Radhakrishnan, Jai, New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, United States
Description
Critical Path Institute’s (C-Path) Predictive Safety Testing Consortium (PSTC) and the Foundation for National Institutes of Health (FNIH) completed preclinical, exploratory clinical, and confirmatory clinical trials to identify and qualify emerging kidney injury biomarkers (EBM) to more sensitively determine presence of renal parenchymal injury. Letters of Support from US FDA and EMA and FDA qualification were issued recommending use of a EBM composite measure (CM: clusterin, cystatin C, KIM-1, NAG, NGAL, osteopontin) to monitor participant safety in single or multiple ascending dose phase 1 trials when preclinical animal toxicology studies showed post-baseline changes in ≥1 EBM. In their review, FDA commented that utility of the EBM CM should be in conjunction with standard kidney safety biomarkers — serum creatinine, blood urea nitrogen, urine albumin-creatinine or protein-creatinine ratio; and increases in ≥1 EBM in the EBM CM provide evidence of renal tubular injury. FDA stipulated that analytical laboratory methodology must be validated to robustly assess EBM sensitivity and specificity; and EBM threshold for clinically significant, post-baseline change must be determined in a product-specific way to ensure generalizability.
EBM panel qualification tools — confirmatory study eCRF casebook, EBM lab specification document, metadata (CDISC, SDTM) standards, and statistical analysis plan — can be made available to qualified researchers upon request via C-Path's Data Analytics Platform (DAP) or Biomarker Data Repository to reduce burden on other EBM researchers utilizing the C-Path/PSTC EBM panel or pursuing EBM discovery. Finally, C-Path’s DAP provides Findable, Accessible, Interoperable, Reusable (FAIR) public access to standard and emerging biomarker data to research future applications of the EBMs to qualified researchers.
Funding
- Other U.S. Government Support (e.g., Dept. of Defense), Commercial Support (e.g., Pharmaceutical Company): Pfizer, Lilly, Merck, AstraZeneca, Amgen, JnJ