Characterization and corroboration of safety signals identified from the US Food and Drug Administration Adverse Event Reporting System, 2008-19: cross sectional study

Abstract

Objective To characterize potential drug safety signals identified from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), from 2008 to 2019, to determine how often these signals resulted in regulatory action by the FDA and whether these actions were corroborated by published research findings or public assessments by the Sentinel Initiative. Design Cross sectional study. Setting USA. Population Safety signals identified from the FAERS and publicly reported by the FDA between 2008 and 2019; and review of the relevant literature published before and after safety signals were reported in 2014-15. Literature searches were performed in November 2019, Sentinel Initiative assessments were searched in December 2021, and data analysis was finalized in December 2021. Main outcome measures Safety signals and resulting regulatory actions; number and characteristics of published studies, including corroboration of regulatory action as evidenced by significant associations (or no associations) between the drug related to the signal and the adverse event. Results From 2008 to 2019, 603 potential safety signals identified from the FAERS were reported by the FDA (median 48 annually, interquartile range 41-61), of which 413 (68.5%) were resolved as of December 2021 (372 of 399 (93.2%) signals ≥3 years old were resolved). Among the resolved safety signals, 91 (22.0%) led to no regulatory action and 322 (78.0%) resulted in regulatory action, including 319 (77.2%) changes to drug labeling and 59 (14.3%) drug safety communications or other public communications from the FDA. For a subset of 82 potential safety signals reported in 2014-15, a literature search identified 1712 relevant publications; 1201 (70.2%) were case reports or case series. Among these 82 safety signals, 76 (92.7%) were resolved, of which relevant published research was identified for 57 (75.0%) signals and relevant Sentinel Initiative assessments for four (5.3%) signals. Regulatory actions by the FDA were corroborated by at least one relevant published research study for 17 of the 57 (29.8%) resolved safety signals; none of the relevant Sentinel Initiative assessments corroborated FDA regulatory action. Conclusions Most potential safety signals identified from the FAERS led to regulatory action by the FDA. Only a third of regulatory actions were corroborated by published research, however, and none by public assessments from the Sentinel Initiative. These findings suggest that either the FDA is taking regulatory actions based on evidence not made publicly available or more comprehensive safety evaluations might be needed when potential safety signals are identified.

Spontaneous reporting of post-market safety signals: what evidence should support regulatory action?

“…To better understand the FDA’s pharmacovigilance efforts, in our linked study in The BMJ ,8 we characterised safety signals identified from FAERS from 2008 to 2019 and determined how often these signals resulted in FDA regulatory actions. Next, among a subset of signals from 2014 and 2015, we ascertained whether these regulatory actions were corroborated by the studies published in the medical literature or by Sentinel Initiative assessments.…”

Radical transparency in post-market oversight of medicine safety

“…In a linked paper (doi:10.1136/bmj-2022-071752), Dhodapkar and colleagues analysed 12 years of safety signals identified within the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) 5. They asked how often these signals resulted in regulatory actions and whether they were corroborated by additional research.…”

Transparency and robustness of safety signals

“…Dhodapkar and colleagues assessed the role and impact of safety signals from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) database on subsequent regulatory actions by the administration 1. Spontaneous reporting systems and analyses of aggregated cases in databases such as FAERS are a cornerstone in generating post-marketing safety signals.…”