J Biopharm Stat. 2026 May 20:1-15. doi: 10.1080/10543406.2026.2670521. Online ahead of print.
ABSTRACT
The hERG safety assay is crucial for assessing the risk of delayed repolarization and QT interval prolongation in investigational drugs, yet a lack of consensus exists on classifying drugs into appropriate risk categories based on assay results. We propose a two-stage statistical framework for quantitative assessment of hERG safety assay classification for investigational products adhering to ICH E14 S7b Q&A Best Practice protocols. Our framework employs a fixed margin equivalence testing approach to evaluate concurrent positive controls against the positive control reference in Stage 1, followed by a logistic regression model based on a T-score to classify the investigational product into two risk categories (QT effect ≥ 10 msec or < 10 msec) in Stage 2. Applied to real-world data, our method demonstrates the ability to classify investigational products with an AUROC of at least 0.9, using a pre-specified probability margin. Additionally, our approach addresses lab-to-lab variability in hERG safety assay assessment, providing a standardized, quantitative method for evaluating hERG assay results that could improve consistency in drug risk assessment across the pharmaceutical industry.
PMID:42160048 | DOI:10.1080/10543406.2026.2670521
