Background: Safety issues for fluoroquinolones have been provided by regulatory agencies. This study was conducted to identify signals of fluoroquinolones reported in the Korea Adverse Event Reporting System (KAERS) using tree-based machine learning (ML) methods.
Research design and methods: All adverse events (AEs) associated with the target drugs reported in the KAERS from 2013 to 2017 were matched with drug label information. A dataset containing label-positive and -negative AEs was arbitrarily divided into training and test sets. Decision tree, random forest (RF), bagging, and gradient boosting machine (GBM) were fitted on the training set with hyperparameters tuned using five-fold cross-validation and applied to the test set. The ML method with the highest area under the curve (AUC) scores was selected as the final ML model.
Results: Bagging was selected as the final ML model for gemifloxacin (AUC score: 1) and levofloxacin (AUC: 0.9987). RF was selected in ciprofloxacin, moxifloxacin, and ofloxacin (AUC scores: 0.9859, 0.9974, and 0.9999 respectively). We found that the final ML methods detected additional signals that were not detected using the disproportionality analysis (DPA) methods.
Conclusions: The bagging-or-RF-based ML methods performed better than DPA and detected novel AE signals previously unidentified using the DPA methods.
Keywords: Disproportionality analysis; fluoroquinolones; signal detection; spontaneous reporting system; tree-based machine learning.