Abstract: INFO15-SA
Blinded, Human-in-the-Loop Adjudicators Assess Earlier Detection of Nephrotoxic Injury in Prospective Studies Supporting a US Food and Drug Administration (FDA) Biomarker Qualification
Session Information
- Informational Posters - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- No subcategory defined
Authors
- Richfield, Owen, Yale University, New Haven, Connecticut, United States
- Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
- Dieterle, Frank, Novartis AG, Basel, BS, Switzerland
- Friedman, Gary Steven, Critical Path Institute, Tucson, Arizona, United States
- Murray, Patrick T., University College Dublin, Dublin, Leinster, Ireland
- Roberts, Glenda V., Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Strader, Michael, University College Dublin, Dublin, Leinster, Ireland
- Sultana, Stefan, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Hoffmann, Steven C., Foundation for the National Institutes of Health, North Bethesda, Maryland, United States
- Camerlingo, Nunzio, Pfizer Inc, New York, New York, United States
- Peron, Katrina Jolene, Critical Path Institute, Tucson, Arizona, United States
- King, Nicholas, Critical Path Institute, Tucson, Arizona, United States
Description
Following biomarker discovery and non-clinical studies pairing biomarkers with histopathologic findings (2009-2012), the Safer and Faster Evidence-based Translation (SAFE-T) Consortium and Predictive Safety Testing Consortium (PSTC) completed exploratory clinical studies. Both received FDA & EMA Letters of Support (2015-2016), encouraging use of pan-nephron, non-standard-of-care urine biomarkers (NBM) in early clinical development drug safety trials. SAFE-T NBM panel (urine alpha-GST, CLU, CysC, KIM-1, NGAL, OPN, urea) & PSTC NBM panel (urine CLU, CysC, KIM-1, NAG, NGAL, OPN) were all corrected to urine creatinine. Both panels are paired with standard-of-care kidney injury biomarkers (SBM)-[serum creatinine, CysC and urea nitrogen] and [urine albumin- and protein-to-creatinine ratios]. The 2025 PSTC biomarker qualification package includes completed exploratory, and SBM+NBM data sets from two additional prospective studies.
SAFE-T exploratory study data provided biomarker sensitivity and specificity thresholds, supporting the use of subset panels in future confirmatory studies. PSTC exploratory studies data analytics provided adjudication guidelines for prospective study, nephrologist-in-the-loop, independent, blinded adjudication. Blinded, independent assessments by 2 panels of 3 different adjudicators achieved consensus when assessing either SBM only (91.8%), NBM only (99.5%), or SBM+NBM (99.5%). The prospective studies SAP prespecified primary and secondary endpoints based upon nephrologist adjudication and programmatic determination of specificities and sensitivities using SBM only, NBM only or SBM+NBM combined.
C-Path’s Biomarker Data Repository (BmDR) continually accrues SBM+NBM data sets from Pharma partners. Beyond specificities and sensitivities documented in our biomarker qualification dossier, randomly selected cohorts of 300 study participants from within the BmDR can be assessed using the PSTC SAP. BmDR SBM+NBM data sets are available to qualified researchers and we anticipate that their periodic re-examination of NBM operating characteristics may support them becoming part of standard-of-care nephrology practice.
Funding
- Critical Path Institute is supported by the Food and Drug Administration (FDA) of the Department of Health and Human Services (HHS) and is 56% funded by the FDA/HHS, totaling $23,740,424, and 44% funded by non-government source(s), totaling $18,881,611. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the U.S. Government. Funding for this work was provided by PSTC member companies (Pfizer, Eli Lilly and Company, Merck Sharp & Dohme, AstraZeneca, Amgen, Janssen Pharmaceuticals).