US Food and Drug Administration Safety Advisories and Reporting to the Adverse Event Reporting System (FAERS)

The US Food and Drug Administration (FDA) and other major regulators regularly issue safety advisories about licensed drugs with new adverse effects that have been documented through observational studies, clinical trials, and spontaneously reported adverse drug events.

To assess the possible effects of a representative group of FDA Drug Safety Communications on the reporting of the specific adverse effect featured in the advisory on new cases reported to the FDA Adverse Event Reporting System (FAERS).

We examined 16 FDA Drug Safety Communications issued from 2010 to 2015 that had not previously been the focus of advisories from regulators in the UK, Canada, or Australia. We compared the reports of the adverse effect in the 8 calendar quarters preceding the advisory and in the 4 quarters following. We measured change in reporting frequency by calculating the event reporting odds ratio (ROR) for the post-warning compared to the pre-warning periods. We defined a credible association of the advisory with increased reporting as a ROR ≥ 2.0 and p value of < 0.05 by Fisher's Exact Test.

We found statistically significant increased reporting for 4/16 advisories with RORs that ranged from 3.9 to 40.6. Three advisories had smaller but still statistically significant increases that were less than the ROR ≥ 2.0 threshold. For 7 advisories, we found no statistically significant changes in reporting.

No consistent pattern or effect was found on spontaneous reporting following these safety advisories. After results were available, we observed that some cases with the largest reporting increase also involved substantial numbers of legal claims. Changes in adverse event reporting following a warning need to be evaluated on a case-by-case basis.