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.

Glucagon‐like peptide‐1 analogues and thyroid cancer: An analysis of cases reported in the European pharmacovigilance database

“…Therefore, information provided by pharmacovigilance databases only represents a small sample of what occurs in a whole population. Since the approval of all the GLP‐1 receptor agonists there is a boxed warning of ‘risk of thyroid C‐cell tumours’ in their labels, this may have resulted in over‐reporting of thyroid cancer events also known as notoriety bias 35 …”

Fournier Gangrene Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Pharmacovigilance Study with Data from the U.S. FDA Adverse Event Reporting System

“…It is a common issue that happens in lots of drugs. A study conducted by Neha et al confirms that notoriety bias does not lead to overreporting in the FAERS database, and the overall disproportionality in signal estimates is not changed by the safety alert [10].…”

“…There are a large number of clinical trials, case reports, and other studies aimed at exploring the potential association between FG and SGLT2 inhibitors. Yet the overall number, follow-up, and size of trials are too low to draw liable conclusions, and patients enrolled in clinical trials cannot fully represent those who can receive a drug prescription in clinical practice, though the randomization procedure minimizes the possibility of bias [ 8 – 10 ]. While case reports are lack of ability to generalize.…”

Hepatitis B Virus Reactivation and Mycobacterial Infections Associated With Ustekinumab: A Retrospective Study of an International Pharmacovigilance Database

“…These may act as contributory factors to the development of HBVr, TB, and AMI ( Wang et al, 2020 ). Fourth, the Weber effect and notoriety bias cannot be ruled out in the current study, although studies showed that they are not common in FASRS ( Hoffman et al, 2014 ; Neha et al, 2021 ).…”