Knowledge-based Graphical Method for Safety Signal Detection in Clinical Trials

Fuente: arXiv
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Main Authors: Vandenhende, Francois, Georgiou, Anna, Georgiou, Michalis, Psaras, Theodoros, Karekla, Ellie, Hadjicosta, Elena
Format: Preprint
Published: 2025
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author Vandenhende, Francois
Georgiou, Anna
Georgiou, Michalis
Psaras, Theodoros
Karekla, Ellie
Hadjicosta, Elena
author_facet Vandenhende, Francois
Georgiou, Anna
Georgiou, Michalis
Psaras, Theodoros
Karekla, Ellie
Hadjicosta, Elena
contents We present a graphical, knowledge-based method for reviewing treatment-emergent adverse events (AEs) in clinical trials. The approach enhances MedDRA by adding a hidden medical knowledge layer (Safeterm) that captures semantic relationships between terms in a 2-D map. Using this layer, AE Preferred Terms can be regrouped automatically into similarity clusters, and their association to the trial disease may be quantified. The Safeterm map is available online and connected to aggregated AE incidence tables from ClinicalTrials.gov. For signal detection, we compute treatment-specific disproportionality metrics using shrinkage incidence ratios. Cluster-level EBGM values are then derived through precision-weighted aggregation. Two visual outputs support interpretation: a semantic map showing AE incidence and an expectedness-versus-disproportionality plot for rapid signal detection. Applied to three legacy trials, the automated method clearly recovers all expected safety signals. Overall, augmenting MedDRA with a medical knowledge layer improves clarity, efficiency, and accuracy in AE interpretation for clinical trials.
format Preprint
id arxiv_https___arxiv_org_abs_2511_18937
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Knowledge-based Graphical Method for Safety Signal Detection in Clinical Trials
Vandenhende, Francois
Georgiou, Anna
Georgiou, Michalis
Psaras, Theodoros
Karekla, Ellie
Hadjicosta, Elena
Computation and Language
I.2
We present a graphical, knowledge-based method for reviewing treatment-emergent adverse events (AEs) in clinical trials. The approach enhances MedDRA by adding a hidden medical knowledge layer (Safeterm) that captures semantic relationships between terms in a 2-D map. Using this layer, AE Preferred Terms can be regrouped automatically into similarity clusters, and their association to the trial disease may be quantified. The Safeterm map is available online and connected to aggregated AE incidence tables from ClinicalTrials.gov. For signal detection, we compute treatment-specific disproportionality metrics using shrinkage incidence ratios. Cluster-level EBGM values are then derived through precision-weighted aggregation. Two visual outputs support interpretation: a semantic map showing AE incidence and an expectedness-versus-disproportionality plot for rapid signal detection. Applied to three legacy trials, the automated method clearly recovers all expected safety signals. Overall, augmenting MedDRA with a medical knowledge layer improves clarity, efficiency, and accuracy in AE interpretation for clinical trials.
title Knowledge-based Graphical Method for Safety Signal Detection in Clinical Trials
topic Computation and Language
I.2
url https://arxiv.org/abs/2511.18937