Systematic Analysis of Adverse Event Reports for Sex Differences in Adverse Drug Events.

Yue Yu,Wei Wang,Liwei Wang,Dingcheng Li,Jun Chen,Hongfang Liu

doi:10.1038/srep24955

Abstract

Increasing evidence has shown that sex differences exist in Adverse Drug Events (ADEs). Identifying those sex differences in ADEs could reduce the experience of ADEs for patients and could be conducive to the development of personalized medicine. In this study, we analyzed a normalized US Food and Drug Administration Adverse Event Reporting System (FAERS). Chi-squared test was conducted to discover which treatment regimens or drugs had sex differences in adverse events. Moreover, reporting odds ratio (ROR) and P value were calculated to quantify the signals of sex differences for specific drug-event combinations. Logistic regression was applied to remove the confounding effect from the baseline sex difference of the events. We detected among 668 drugs of the most frequent 20 treatment regimens in the United States, 307 drugs have sex differences in ADEs. In addition, we identified 736 unique drug-event combinations with significant sex differences. After removing the confounding effect from the baseline sex difference of the events, there are 266 combinations remained. Drug labels or previous studies verified some of them while others warrant further investigation.

Highlights

Increasing evidence has shown that sex differences exist in Adverse Drug Events (ADEs)
Increasing evidence has shown that sex differences exist in ADEs, which may be attributed to sex differences in pharmacokinetics and pharmacodynamics[9,10], immunology[11,12], and genetics[13,14]
We reported a systematic analysis of sex differences of ADEs using data from FAERS for the top 20 long-term treatment regimens in the US pharmaceutical market in 2013 where drugs were normalized to RxNorm[23] and aggregated into NDF-RT (National Drug File Reference Terminology)[24] drug classes and adverse events coded using MedDRA (Medical Dictionary for Regulatory Activities)[25] were classified into 26 System Organ Classes (SOCs)

Summary

Result

Detect sex difference in drug-event combination frequency distribution for treatment regimens/drugs. We first tested the treatment regimens/drugs that show sex difference in drug-event combination frequency distributions summarized at SOC level. Those specific ADE signals with sex differences significant at. Blue cells represent the log[2] ROR > 0 (ROR > 1), indicating that the female patients are more likely to report these drug-event combinations. The right cluster shows SOC categories with higher RORs in female patients, including ear and labyrinth disorders; musculoskeletal and connective tissue disorders; and gastrointestinal disorders. Some of these findings have been reported previously.

Discussion

Findings

Methods