FDA FAERS Analysis: Rising Trends in Serious Adverse Events Reports

This blog features:

1. A discussion on adverse event reporting in the FDA and FAERS databases.
2. An overview of reporting involving rising trends in serious adverse events in the US FDA pharmacovigilance system.

Introduction

In this article we discuss about the trends of adverse event reporting which are commonly happening with the regulatory authorities. The findings were based on data available to the public from the FDA quarterly post-marketing FAERS safety data files from 2004 to 2014.

Definitions

Federal regulations define adverse drug events as those “associated with the use of a drug in humans whether or not considered drug related.

Serious adverse events (AEs) are defined by the regulation as those involving death, a life-threatening adverse drug experience, inpatient hospitalisation or prolongation of existing hospitalisation, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

Unexpected AEs are defined as those involving any adverse drug experience that is not listed in the current labeling for the drug product.

Serious and unexpected events are classified as expedited, and manufacturers receiving any such reports are mandated to forward them to the FDA as soon as possible but in no case later than 15 calendar days of the initial receipt of the information.

Trends in Reporting of Serious and Unexpected Events

1. Between 1998 and 2005, serious adverse event (SAE) reports increased 2.6-fold, from 34,966 to 89,842 cases.
2. Fatal adverse drug event reports increased 2.7-fold during the same period, rising from 5,519 to 15,107 cases.
3. Reported serious adverse events increased nearly four times faster than the growth in outpatient prescription use over the decade.
4. FDA FAERS/AERS data collected between January 1, 2004, and June 30, 2014, included only expedited reports that were required to be submitted within 15 calendar days.
5. Direct reports submitted to the FDA without manufacturer involvement were excluded from the analysis.
6. More than 1.6 million adverse event reports were reviewed in the study.
7. Approximately 160,000 reports (nearly 10%) were not received by the FDA within the mandatory 15-day reporting timeline.
8. Among the delayed reports, more than 40,000 involved patient deaths.
9. A separate JAMA Internal Medicine review of approximately 1.27 million adverse event reports also found that nearly 10% of reports failed to meet the required 15-day reporting deadline.
10. More than half of all AERS reports submitted between 1969 and 2009 were received during the most recent 10-year period alone.
11. Report volumes increased at an average annual rate of 11.3% between 2000 and 2010.
12. Reporting rates increased from 4.90 reports per 10,000 physician office visits in 2000 to 6.83 reports per 10,000 visits in 2005.
13. Women accounted for a slightly higher proportion of adverse event reports (55.3%).
14. Among reports with documented outcomes, 42% involved hospitalization.
15. Approximately 15.1% of reports with documented outcomes involved patient deaths.
16. Significant limitations in report quality were identified, including missing age information in 37.4% of reports and missing sex information in 7.5% of reports.
17. The World Health Organization (WHO) estimates that 1 in 10 patients experiences harm while receiving hospital care.
18. WHO also reports that unsafe surgical procedures may lead to complications in up to 25% of patients.

Conclusion

The analysis reveals a significant rise in reported deaths and serious adverse events associated with drug therapy throughout the study period, underscoring the growing importance of pharmacovigilance in protecting public health. These findings emphasize the urgent need for stronger risk management systems, improved safety monitoring practices, and greater transparency in adverse event reporting.

The study also suggests that delays in reporting serious adverse events to the FDA remain a critical concern. Notably, reports involving patient deaths appeared more likely to experience delayed submission. Such delays can impact timely safety evaluations and regulatory actions, highlighting the importance of strict compliance with expedited reporting requirements to ensure patient safety and effective regulatory oversight.