A Feasibility Study of Drug–Drug Interaction Signal Detection in Regular Pharmacovigilance

Journal article

PurposeTo evaluate the impact of multiple design criteria for reference sets that are used to quantitatively assess the performance of pharmacovigilance signal detection algorithms (SDAs) for drug-drug interactions (DDIs).MethodsStarting from a large and diversified reference set for two-way DDIs, we generated custom-made reference sets of various sizes considering multiple design criteria (e.g., adverse event background prevalence). We assessed differences observed in the performance metrics of three different SDAs when applied to FDA Adverse Event Reporting System (FAERS) data.ResultsFor some design criteria, the impact on the performance metrics was neglectable for the different SDAs (e.g., theoretical evidence associated with positive controls), while others (e.g., restriction to designated medical events, event background prevalence) seemed to have opposing and effects of different sizes on AUC and PPV estimates.ConclusionsThe relative composition of reference sets can significantly impact the evaluation metrics, potentially altering the conclusions regarding which methodologies are perceived to perform best. We therefore need to carefully consider the selection of controls to avoid misinterpretation of signals triggered by confounding factors rather than true associations as well as adding biases to our evaluation by "favouring" some algorithms while penalising others. This article is protected by copyright. All rights reserved

Authors: Hult, S; Sartori, D; Bergvall, T; Hedfors Vidlin, S; Grundmark, B

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Drug Safety: The Official Journal of the International Society of Pharmacovigilance
• Volume: 43
• Issue: 8
• Pages: 775-785
• Publication date: 2020-07-17
• DOI: 10.1007/s40264-020-00939-y
• EISSN: 1179-1942
• ISSN: 0114-5916
• Language: English
• Keywords: Medicine; Adverse effect; Drug development; Drug interaction; Drug; Pharmacology; Pharmacovigilance; Adverse drug reaction