Inside the World’s Four Giant Drug Safety Databases: Billions of Reports, Hidden Overlaps

Every year, millions of patients, doctors, pharmacists, and lawyers around the world file reports when something goes wrong after taking a medicine or getting a vaccine. These reports flow into a handful of enormous databases that together form the backbone of modern pharmacovigilance, the science of detecting drug safety signals after medicines reach the market. Now, researchers in Spain have carried out the first comprehensive side-by-side comparison of the four largest spontaneous reporting systems on the planet, revealing striking differences in who reports, what gets reported, and how the pandemic reshaped the entire landscape of drug safety surveillance.

The study, led by Nikola Panajotovikj and Jordi Mestres of Chemotargets SL and the University of Girona, examined VigiBase, the World Health Organization’s global database maintained by the Uppsala Monitoring Centre; the FDA Adverse Event Reporting System, known as FAERS; the Vaccine Adverse Event Reporting System, or VAERS, co-managed by the FDA and the Centers for Disease Control and Prevention; and Japan’s Adverse Drug Event Report database, called JADER, run by the Pharmaceuticals and Medical Devices Agency. As of December 31, 2025, these four systems collectively held roughly 72.3 million reports, with VigiBase alone containing approximately 42.4 million, FAERS 26.3 million, VAERS 2.7 million, and JADER 0.9 million. The findings were published in Frontiers in Drug Safety and Regulation.

One of the most technically demanding parts of the work involved deduplication, the process of identifying reports that appear in more than one database. Because national regulators forward cases to VigiBase while also filing directly with systems like FAERS, the same adverse event can exist in multiple repositories simultaneously. The researchers used a content-matching algorithm that compared drug codes, adverse event terms, time to onset, indication, basis of report, event date, sex, region, and age, harmonizing drug names through the WHO Drug Dictionary and the Anatomical Therapeutic Chemical classification system, and matching adverse events at the MedDRA Preferred Term level. Duplicates were classified into three tiers: exact matches on every field, near-matches differing by a single missing element, and near-matches differing by a single character in one field.

The results of this deduplication effort were striking. After removing duplicates, VigiBase retained 39.5 million reports, of which 27.0 million, or 68.4 percent, were exclusive to that database. FAERS retained 20.3 million reports with 9.1 million, or 44.8 percent, being unique. VAERS was left with 2.3 million reports, 41.5 percent of which were exclusive, while JADER kept nearly all of its 0.9 million reports, with 92.4 percent being unique. Critically, the analysis revealed that VigiBase incorporates more than half of the entire contents of both FAERS, at 54.7 percent, and VAERS, at 56.5 percent. This substantial overlap means that researchers who naively combine data from multiple databases without accounting for duplicates risk double-counting the same adverse events, potentially inflating statistical signals and distorting safety conclusions.

The COVID-19 pandemic left an indelible mark on these databases, though its impact varied dramatically depending on each system’s regulatory mandate. In VAERS, which is specifically designed to capture vaccine-related reports, a staggering 57.8 percent of all reports relate to a COVID-19 vaccine. VigiBase saw 13.9 percent of its reports linked to COVID-19 vaccines, while JADER recorded 3.7 percent. FAERS, by contrast, remained almost untouched at just 0.3 percent, because the US regulatory framework directs vaccine reports to VAERS rather than to the general drug safety system. The pandemic’s influence on database composition is so pronounced that the researchers excluded all COVID-19 vaccine reports from their temporal trend analyses to avoid obscuring underlying patterns in drug safety reporting.

Temporal analysis revealed that these databases are growing at an accelerating pace. Approximately 40 percent of all reports in VigiBase were received in just the past five years, and 70 percent within the past ten years. FAERS collected 40 percent of its reports in the last eight years and 70 percent in the last fourteen years, with similar patterns observed for JADER. VAERS experienced the most dramatic acceleration, accumulating 70 percent of all its reports in just seven years, driven largely by the pandemic. When COVID-19 vaccine reports were excluded, the timeline for reaching these milestones extended considerably, particularly for VAERS, where the 70 percent threshold shifted from seven years to seventeen years.

Perhaps the most culturally revealing findings concern who files these reports. In FAERS, consumers dominate, submitting 53.4 percent of all reports, followed by physicians at 25.0 percent. In stark contrast, JADER is overwhelmingly physician-driven, with doctors filing 70.5 percent of reports, reflecting a Japanese pharmacovigilance framework that relies heavily on healthcare professionals. VigiBase occupies a middle ground, with a nearly balanced distribution between consumers at 41.2 percent and physicians at 39.7 percent. Interestingly, lawyer-reported cases, while rare across all databases, are most prominent in FAERS at 2.5 percent, potentially reflecting litigation-driven reporting patterns in the United States.

Demographic patterns also diverged significantly across systems. Female patients are over-represented in VigiBase, FAERS, and VAERS, accounting for 60.4, 60.3, and 64.8 percent of reports respectively, a pattern that may reflect women’s higher healthcare engagement and greater susceptibility to certain adverse events. JADER stands out as a notable exception, with an almost equal sex distribution at 48.9 percent female and 51.1 percent male. Age distributions tell equally distinct stories: JADER reports skew heavily toward elderly patients, with 42.3 percent in the retirement category of 75 years and older, consistent with Japan’s ageing population and associated polypharmacy burden. VAERS shows a higher proportion of paediatric reports, reflecting routine childhood immunization schedules in the United States.

When the researchers compared reporting patterns before and after January 1, 2015, excluding COVID-19 vaccine reports, they found consistent shifts across all four systems. Consumer reporting increased markedly in VigiBase, rising from 29.7 to 41.6 percent, while physician reporting declined from 53.7 to 36.4 percent. Similar trends appeared in FAERS and JADER, suggesting a global movement toward greater patient involvement in pharmacovigilance. The proportion of reports involving antineoplastic and immunomodulating agents rose substantially across all databases, reflecting the surge in oncology and immunotherapy approvals in recent years. Meanwhile, reports of medication errors and product use issues increased dramatically, from 1.4 to 5.1 percent in FAERS and from 1.3 to 5.0 percent in VigiBase, a trend the researchers attribute to the increasing formalization of medication error concepts within pharmacovigilance coding practices rather than a true rise in error frequency.

The study also quantified each database’s capacity to generate statistical safety signals using the proportional reporting ratio, a disproportionality measure that flags drug-event pairs reported more frequently than expected. FAERS produced the largest absolute number of signals at 1,616,441, followed by VigiBase at 1,203,070, VAERS at 107,390, and JADER at 96,174. When normalized by the size of each database’s drug-event vocabulary, FAERS again led with a signal yield of 21.1 percent, followed by VigiBase at 16.1 percent, VAERS at 11.0 percent, and JADER at 9.8 percent. Notably, of the 2,021,522 unique signals identified across all four databases, only 0.1 percent were detected in all four simultaneously, while 54.6 percent were exclusive to a single database. This striking lack of overlap underscores the complementary nature of these systems and reinforces the argument that multi-database signal detection strategies, when properly deduplicated and interpreted in light of each system’s unique characteristics, offer the most comprehensive picture of post-marketing drug safety worldwide.

Subject of Research: Comparative analysis of global spontaneous adverse event reporting systems for drug and vaccine safety surveillance

Article Title: Global patterns and trends in spontaneous reporting systems: VigiBase, FAERS, VAERS, and JADER

Article References: Panajotovikj, N., & Mestres, J. (2026). Global patterns and trends in spontaneous reporting systems: VigiBase, FAERS, VAERS, and JADER. Frontiers in Drug Safety and Regulation, 6, Article 1919822. https://doi.org/10.3389/fdsfr.2026.1919822

Image Credits: AI Generated

DOI: 10.3389/fdsfr.2026.1919822

Keywords: pharmacovigilance, VigiBase, FAERS, VAERS, JADER, adverse drug events, drug safety signals, COVID-19 vaccines, deduplication, disproportionality analysis, spontaneous reporting, post-marketing surveillance