Existence of Notoriety Bias in FDA Adverse Event Reporting System Database and Its Impact on Signal Strength.

Abstract

Background: Notoriety bias is defined as "a selection bias in which a case has a greater chance of being reported if the subject is exposed to the studied factor known to cause, thought to cause, or likely to cause the event of interest." This study aimed to determine the existence of notoriety bias in the FDA Adverse Event Reporting System (FAERS) database and estimate the impact of potential notoriety bias induced by safety alerts on signal estimation using disproportionality analysis. Methods: Publicly available FAERS data were downloaded and used for analysis. Thirty-one drugs which had label change/safety alert issued by FDA from 2009 to 2013 were considered. These drugs were reviewed 4 quarters before and after the safety alert notification for the existence of notoriety bias. The impact of notoriety bias induced by safety alerts was analyzed by comparing the signal strength using reporting odds ratio (ROR) and proportional reporting ratio (PRR), 2 years before and after the safety alert. Wilcoxon signed rank test was used to determine whether there were a statistically significant difference before and after the safety alert. Results: There was increased reporting for 11 drugs after the safety alert/label change by the FDA. The reporting of 20 drugs decreased or remained unchanged after the safety alert/label change by the FDA. Wilcoxon signed rank test showed that there is no statistically significant difference with respect to the number of reports before and after the safety alert (P = .330, Z = -0.974). Fourteen (45.16%) drugs had an increase in ROR, while 17 (54.83%) drugs had a decrease in ROR after safety alert issued by FDA (P = .953, Z = -0.059). Fourteen (45.16%) drugs had an increase in PRR, while 17 (54.83%) drugs had a decrease in PRR after safety alert issued by the FDA (P = .914, Z = -0.108). Conclusion: Although few FDA safety alert/warnings had a strong and immediate impact, many had no impact on reporting of AE and signal strength. This study found that overreporting due to notoriety bias does not exist in the FAERS database and the overall disproportionality in signal estimates is not altered by the safety alert.