Leveraging the Variability of Pharmacovigilance Disproportionality Analyses to Improve Signal Detection Performances.

Frontiers in Pharmacology
Charles KhouriJean-Luc Cracowski

Abstract

Background: A plethora of methods and models of disproportionality analyses for safety surveillance have been developed to date without consensus nor a gold standard, leading to methodological heterogeneity and substantial variability in results. We hypothesized that this variability is inversely correlated to the robustness of a signal of disproportionate reporting (SDR) and could be used to improve signal detection performances. Methods: We used a validated reference set containing 399 true and false drug-event pairs and performed, with a frequentist and a Bayesian disproportionality method, seven types of analyses (model) for which the results were very unlikely to be related to actual differences in absolute risks of ADR. We calculated sensitivity, specificity and plotted ROC curves for each model. We then evaluated the predictive capacities of all models and assessed the impact of combining such models with the number of positive SDR for a given drug-event pair through binomial regression models. Results: We found considerable variability in disproportionality analysis results, both positive and negative SDR could be generated for 60% of all drug-event pairs depending on the model used whatever their truthfulness. Furtherm...Continue Reading

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Citations

Aug 17, 2021·JAMA Internal Medicine·Charles KhouriJean-Luc Cracowski

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Software Mentioned

EudraVigilance
Vigibase

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