Abstract
Purpose
We proposed a statistical criterion to detect drug-drug interactions causing adverse drug reactions in spontaneous reporting systems.
Methods
The used criterion quantitatively measures the discrepancy between the observed and expected number of adverse events via chi-square statistics. We compared the performance of our method with that of Norén et al. (Stat Med 2008; 27 (16): 3057–3070) through a simulation study.
Results
When the number of events for a combination of two drugs was equal to or lower than two, the false positive rate for our method ranged from 0.01 to 0.08, whereas the rate for Norén’s method ranged from 0.01 to 0.06. The sensitivity for our method ranged from 0.09 to 0.29, whereas the sensitivity for Norén’s method ranged from 0.03 to 0.24. The area-under-the-receiver operating characteristic curve for our method was significantly larger than that for Norén’s methods regardless of simulation settings. The proposed method was also applied to the Food and Drug Administration Adverse Event Reporting System database, and a recognized drug-drug interaction was detected.
Conclusions
The proposed criterion controlled false positives at an acceptable level and had higher sensitivity than that of Norén’s method had when events were rare.
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Acknowledgements
This study was supported by JSPS KAKENHI Grant Number 15K19219.
Contributions of authors
M.G. was responsible for study concept, analysis and interpretation of results, and wrote the first draft of the manuscript. K.M. and A.H. interpreted the study results. K.T. reviewed the simulation code. All authors elaborated and revised the manuscript.
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Gosho, M., Maruo, K., Tada, K. et al. Utilization of chi-square statistics for screening adverse drug-drug interactions in spontaneous reporting systems. Eur J Clin Pharmacol 73, 779–786 (2017). https://doi.org/10.1007/s00228-017-2233-3
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DOI: https://doi.org/10.1007/s00228-017-2233-3