Identifying Drug-Drug Interactions in Spontaneous Reports Utilizing Signal Detection and Biological Plausibility Aspects.

Kontsioti, Elpida, Maskell, Simon ORCID: 0000-0003-1917-2913, Anderson, Isobel and Pirmohamed, Munir ORCID: 0000-0002-7534-7266 (2024) Identifying Drug-Drug Interactions in Spontaneous Reports Utilizing Signal Detection and Biological Plausibility Aspects. Clinical pharmacology and therapeutics.

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Official URL: http://dx.doi.org/10.1002/cpt.3258

Abstract

Translational approaches can benefit post-marketing drug safety surveillance through the growing availability of systems pharmacology data. Here, we propose a novel Bayesian framework for identifying drug-drug interaction (DDI) signals and differentiating between individual drug and drug combination signals. This framework is coupled with a systems pharmacology approach for automated biological plausibility assessment. Integrating statistical and biological evidence, our method achieves a 16.5% improvement (AUC: from 0.620 to 0.722) with drug-target-adverse event associations, 16.0% (AUC: from 0.580 to 0.673) with drug enzyme, and 15.0% (AUC: from 0.568 to 0.653) with drug transporter information. Applying this approach to detect potential DDI signals of QT prolongation and rhabdomyolysis within the FDA Adverse Event Reporting System (FAERS), we emphasize the significance of systems pharmacology in enhancing statistical signal detection in pharmacovigilance. Our study showcases the promise of data-driven biological plausibility assessment in the context of challenging post-marketing DDI surveillance.

Item Type:	Article
Uncontrolled Keywords:	Patient Safety
Divisions:	Faculty of Health and Life Sciences Faculty of Science and Engineering > School of Electrical Engineering, Electronics and Computer Science Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	17 Apr 2024 09:10
Last Modified:	17 Apr 2024 13:18
DOI:	10.1002/cpt.3258
Open Access URL:	https://doi.org/10.1002/cpt.3258
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3180391