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

The retrospective descriptive study, conducted by Mikyung Kim and Dong-jun Choi of the Department of Internal Medicine and the Regional Pharmacovigilance Center for Korean Herbal Medicines, mined the shared adverse event reporting databases of the two hospitals. After removing duplicates, the researchers identified 454 reports in which an herbal medicine was recorded as the suspected agent. That figure represents just 1.2 percent of the 38,367 adverse event reports handled by the centers over the entire study period, a proportion that itself hints at how rarely herbal products are formally flagged as suspected causes of harm even in institutions where they are prescribed routinely.

The most striking finding concerns the regulatory status of the products involved. Non-licensed oral herbal medicines accounted for the largest share of suspected agents at 48.7 percent, narrowly exceeding the 47.0 percent share of oral herbal medicine products licensed by Korea’s Ministry of Food and Drug Safety. At the report level, 51.3 percent of cases involved at least one non-licensed formulation. These are preparations that fall outside the standard regulatory licensing pathway, including individualized herbal decoctions compounded for specific patients, and they are precisely the products that national databases built around licensed pharmaceuticals are least equipped to track.

The clinical profile of the reported events followed recognizable patterns. Gastrointestinal disorders were the most frequently reported system organ class, classified according to the Medical Dictionary for Regulatory Activities, followed by skin and subcutaneous tissue disorders. Among the 572 drug-event pairs with evaluable causality assessments, the overwhelming majority, 87.7 percent, were judged merely possible, while cases assessed as certain were vanishingly rare at 0.2 percent. That distribution reflects a familiar limitation of spontaneous reporting: without rechallenge or unambiguous temporal and biological evidence, causality in herbal medicine cases usually remains provisional, complicated by polypharmacy, delayed onset, and the multi-component nature of herbal formulas.

The surveillance gap emerges most clearly when the researchers compared reports that were forwarded to the national system with those that were not. Overall, 24.0 percent of the 454 reports were never submitted to national pharmacovigilance. The differences between the two groups were stark and statistically significant. Non-submitted reports far more frequently involved non-licensed herbal medicines, at 83.5 percent compared with 41.2 percent of submitted reports. They were far less likely to include documented clinical severity grading, at 7.3 percent versus 59.1 percent, and far less likely to contain a causality assessment, at 26.6 percent versus 98.8 percent, with p values below 0.001 across all three comparisons.

In other words, the reports most likely to slip through the cracks were those describing the products least visible to regulators, and those least complete in the clinical detail that pharmacovigilance assessment depends on. Severity grading in the study followed the Common Terminology Criteria for Adverse Events, the standardized scale used in oncology and increasingly across drug safety work, while causality was evaluated within the framework of individual case safety reports submitted through Korea’s adverse event reporting infrastructure. A report lacking both a severity grade and a causality judgment offers national assessors little to work with, which may partly explain why incomplete cases were not prioritized for submission.

The structural reasons behind the gap are not difficult to infer from the Korean context. Traditional Korean medicine doctors routinely prescribe individualized multi-herb decoctions that are compounded fresh for each patient. These formulations do not carry product licenses in the way manufactured drugs do, so they sit awkwardly within a reporting system whose data structures, coding conventions, and regulatory workflows were designed around licensed medicinal products. A suspected reaction to a ten-herb decoction does not map neatly onto a single product code, and the paper’s authors argue that the current pharmacovigilance framework therefore does not fully capture the range of herbal medicines actually used in real-world Korean practice.

The study’s setting gives its findings particular weight. Dongguk University Ilsan Oriental Hospital hosts a regional pharmacovigilance center specifically dedicated to Korean herbal medicines, one of the institutional mechanisms Korea has built to strengthen reporting from the traditional medicine sector. If, even at a center with dedicated reporting infrastructure, a quarter of herbal adverse event reports failed to reach the national system and half involved non-licensed formulations, the authors suggest that the true blind spots in less specialized settings are likely to be larger. Fifteen years of data also lend temporal depth, spanning a period in which Korea expanded its pharmacovigilance networks and electronic reporting systems considerably.

The methodological caveats are worth noting. This was a single-center retrospective descriptive analysis, so the absolute numbers and proportions cannot be generalized to the whole country, and spontaneous reporting data inherently capture only a fraction of adverse events that actually occur, with underreporting the norm rather than the exception across all drug classes. The study was exempted from full ethical review because it used de-identified data from previously collected reports. Still, the internal comparison between submitted and non-submitted reports is the analytically powerful part of the design, because both groups came from the same institutions over the same period, isolating the characteristics that predict whether a case enters national surveillance.

The authors’ conclusions point toward concrete reforms: broader surveillance coverage that explicitly encompasses non-licensed formulations, improved documentation of clinical severity and causality assessments at the point of reporting, and stronger reporting support for traditional Korean medicine professionals, who are often the first and only clinicians positioned to recognize a herbal adverse event. As herbal medicine use grows globally and integrative care models spread, the Korean experience offers a cautionary lesson for any country attempting to fold traditional formulations into regulatory safety systems built for licensed pharmaceuticals. A safety net with holes in exactly the places where the most-used products fall through is, the study implies, a net that needs reweaving.

Subject of Research: Herbal medicine adverse event reporting and pharmacovigilance surveillance gaps in traditional Korean medicine

Article Title: Real-world patterns of herbal medicine-related adverse event reports and surveillance gaps in national pharmacovigilance: a 15-year retrospective analysis from a single integrative medical center in Korea

Article References: Kim, M., & Choi, D.-J. (2026). Real-world patterns of herbal medicine-related adverse event reports and surveillance gaps in national pharmacovigilance: a 15-year retrospective analysis from a single integrative medical center in Korea. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05532-x

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05532-x

Keywords: pharmacovigilance, herbal medicine, adverse event reporting, traditional Korean medicine, drug safety, non-licensed formulations, spontaneous reporting, causality assessment, real-world data, Korea, integrative medicine, surveillance gap