Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase®

Abstract

Introduction The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and VigiBase ® are two established databases for safety monitoring of medicinal products, recently complemented with the EudraVigilance Data Analysis System (EVDAS). Objective Signals of disproportionate reporting (SDRs) can characterize the reporting profile of a drug, accounting for the distribution of all drugs and all events in the database. This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA). Methods SDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase ®). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA ® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA ® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided by SDRs from any database) and overlap (SDRs in EVDAS and at least one other database, divided by SDRs in EVDAS). Covariates with potential impact on results were explored with linear regression models. Results The median overlap between EVDAS and FAERS or VigiBase ® was 85.0% at the PT level, 94.5% at the HLT level, and 97.7% at the HLT or SMQ level. The corresponding median recall of signals in EVDAS as a percentage of all signals generated in all three databases was 59.4%, 74.1%, and 87.9% at the PT, HLT, and HLT or SMQ levels, respectively. The overlap difference is partially explained by the relative number of EU cases in EudraVigilance and the ratio of EVDAS cases and FAERS cases, presumably due to differences in marketing authorizations, or market penetration in different regions. Products with few cases in EVDAS (< 1500) also display limited recall of signals relative to FAERs/VigiBase ®. Time-on-market does not predict signal redundancy between the three databases. The choice of the DPA has an expected but somewhat small effect on redundancy. Conclusions Organizations typically consider regulatory expectations, operating performance (e.g., positive predictive value), and procedural complexity when selecting databases for signal management. As SDRs can be seen as a proxy of general reporting characteristics identifiable in a systematic screening process, our results indicate that, for most products, these characteristics are largely similar in each of the databases.

Cardiovascular Safety Profile of Romosozumab: A Pharmacovigilance Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS)

“…While reports by healthcare professionals and consumers are voluntary, all suspected ADRs received by marketing authorization holders regarding a product are required to be submitted to the FDA. Similar pharmacovigilance databases exist, including the European Union (EU) database EudraVigilance [ 22 ], as well as the World Health Organization (WHO) VigiBase [ 23 ], which contains all case safety reports submitted by WHO member countries [ 24 ]. While the geographical region of focus is different between these databases, with FAERS predominantly covering the US, EudraVigilance covering the European Union, and VigiBase with a global focus, previous studies have identified overlapping results [ 24 , 25 ].…”

Leveraging the Variability of Pharmacovigilance Disproportionality Analyses to Improve Signal Detection Performances

“…The findings of our study may not be generalizable to other databases due to differences related to the database background and the medical products covered. Nevertheless, several studies have highlighted the similitudes and overlaps between SDR found from pharmaceutical company databases and international pharmacovigilance databases (Candore et al, 2015;Vogel et al, 2020). Finally, while it can be assumed that the results are applicable to other drug events pairs, the predicted probabilities calculated in this study are not extrapolable.…”

SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database

“…21 Nevertheless, recent studies show similar sensitivity for EudraVigilance compared to other databases for safety monitoring of medicinal products such as VigiBase or the FDA Adverse Event Reporting System. 22 Fourth, the mean latency period was 15.3 months. Nevertheless, data were not available for almost half of the reports.…”

“…We could not gather information about the body mass index, which is a known risk factor for developing bladder cancer 21 . Nevertheless, recent studies show similar sensitivity for EudraVigilance compared to other databases for safety monitoring of medicinal products such as VigiBase or the FDA Adverse Event Reporting System 22 . Fourth, the mean latency period was 15.3 months.…”