Gregory E Powell

Jeffery L Painter, François Haguinet, Gregory E Powell et al.

Semantic similarity measures (SSMs) are widely used in biomedical research but remain underutilized in pharmacovigilance. This study evaluates six ontology-based SSMs for clustering MedDRA Preferred Terms (PTs) in drug safety data. Using the Unified Medical Language System (UMLS), we assess each method's ability to group PTs around medically meaningful centroids. A high-throughput framework was developed with a Java API and Python and R interfaces support large-scale similarity computations. Results show that while path-based methods perform moderately with F1 scores of 0.36 for WUPALMER and 0.28 for LCH, intrinsic information content (IC)-based measures, especially INTRINSIC-LIN and SOKAL, consistently yield better clustering accuracy (F1 score of 0.403). Validated against expert review and standard MedDRA queries (SMQs), our findings highlight the promise of IC-based SSMs in enhancing pharmacovigilance workflows by improving early signal detection and reducing manual review.

Jeffery L Painter, Gregory E Powell, Andrew Bate

Reliable drug safety reference databases are essential for pharmacovigilance, yet existing resources like SIDER are outdated and static. We introduce PVLens, an automated system that extracts labeled safety information from FDA Structured Product Labels (SPLs) and maps terms to MedDRA. PVLens integrates automation with expert oversight through a web-based review tool. In validation against 97 drug labels, PVLens achieved an F1 score of 0.882, with high recall (0.983) and moderate precision (0.799). By offering a scalable, more accurate and continuously updated alternative to SIDER, PVLens enhances real-time pharamcovigilance with improved accuracy and contemporaneous insights.

François Haguinet, Jeffery L Painter, Gregory E Powell et al.

We present a Bayesian dynamic borrowing (BDB) approach to enhance the quantitative identification of adverse events (AEs) in spontaneous reporting systems (SRSs). The method embeds a robust meta-analytic predictive (MAP) prior with a Bayesian hierarchical model and incorporates semantic similarity measures (SSMs) to enable weighted information sharing from clinically similar MedDRA Preferred Terms (PTs) to the target PT. This continuous similarity-based borrowing overcomes limitations of rigid hierarchical grouping in current disproportionality analysis (DPA). Using data from the FDA Adverse Event Reporting System (FAERS) between 2015 and 2019, we evaluate our approach -- termed IC SSM -- against traditional Information Component (IC) analysis and IC with borrowing at the MedDRA high-level group term level (IC HLGT). A reference set (PVLens), derived from FDA product label update, enabled prospective evaluation of method performance in identifying AEs prior to official labeling. The IC SSM approach demonstrated higher sensitivity (1332/2337=0.570, Youden's J=0.246) than traditional IC (Se=0.501, J=0.250) and IC HLGT (Se=0.556, J=0.225), consistently identifying more true positives and doing so on average 5 months sooner than traditional IC. Despite a marginally lower aggregate F1-score and Youden's index, IC SSM showed higher performance in early post-marketing periods or when the detection threshold was raised, providing more stable and relevant alerts than IC HLGT and traditional IC. These findings support the use of SSM-informed Bayesian borrowing as a scalable and context-aware enhancement to traditional DPA methods, with potential for validation across other datasets and exploration of additional similarity metrics and Bayesian strategies using case-level data.