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 investigation, published in Breast Cancer Research and Treatment, was led by dermatologists and oncologists affiliated with the European Academy of Dermatology and Venereology Task Force Dermatology for Cancer Patients, with first author Ioannis-Alexios Koumprentziotis of the National and Kapodistrian University of Athens coordinating a network spanning Greece, the United Kingdom, France, Poland, and Italy. The team pursued a deliberately triangulated design. At its core sat a retrospective cohort of 56 breast cancer patients treated with sacituzumab govitecan and clinically assessed by dermatologists at participating centers. That clinical cohort was then cross-checked against two independent pharmacovigilance sources: the World Health Organization’s global adverse event database VigiBase, which contributed 696 individual case safety reports, and the French Pharmacovigilance Database, which added 46 cases. Finally, the authors reviewed the published literature from clinical trials that reported dermatologic adverse events, allowing them to compare spontaneous reporting signals with the more controlled environment of prospective trials.

Across every data source, one finding towered above the rest: alopecia, or hair loss, was by far the most frequently reported dermatologic adverse event. In the EADV clinical cohort, 41.1 percent of patients experienced it; in the French database the figure rose to 52.2 percent, and in VigiBase it reached 67.6 percent of reported cases. That gradient is itself informative, because spontaneous reporting systems tend to overrepresent dramatic or highly visible events, and few toxicities are as visible as hair loss. Behind alopecia came a consistent cluster of inflammatory and barrier-related conditions: stomatitis and mucositis, the painful ulceration of the mouth’s lining; pruritus, or generalized itching; xerosis, the abnormal dryness of the skin; and maculopapular rash, the classic raised, blotchy eruption familiar from many targeted cancer therapies. In the EADV cohort, clinicians identified 13 distinct dermatologic event types in total, a spectrum broad enough that the authors argue dermatologic monitoring should be considered a routine component of care rather than an afterthought.

The severity data are where the study delivers its most reassuring message. Using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, the standard grading scale in oncology, the researchers found that 96.4 percent of dermatologic events in the clinical cohort were grade 1 or grade 2, meaning mild to moderate. Median time to the first dermatologic event was 56 days, roughly two months into treatment, which gives clinicians a concrete window during which heightened vigilance is most useful. Most strikingly, treatment discontinuation attributable to dermatologic adverse events occurred in only 3.6 percent of patients. In other words, while skin and hair toxicity is common and can meaningfully affect quality of life, it rarely forces patients off a drug that may be extending their survival. That distinction between frequency and consequence is central to how oncologists weigh a therapy’s tolerability, and it positions sacituzumab govitecan’s cutaneous profile as manageable rather than limiting.

The pharmacovigilance arm of the study used disproportionality analysis, a statistical technique that asks whether a particular drug–event pair is reported together more often than would be expected by chance within a vast database of spontaneous reports. The standard metric here is the information component, or IC, derived from Bayesian statistics, with confidence intervals that exclude zero indicating a genuine reporting signal. In VigiBase, the analysis confirmed significant signals for alopecia, with an IC of 3.3 and a confidence interval of 3.09 to 3.53, a strong signal consistent with the drug’s known biology. Infusion-related reactions also emerged with an IC of 1.9, and stomatitis produced a signal with an IC of 1.6. These quantitative findings align neatly with the clinical cohort, a convergence the authors interpret as mutual validation: the dermatologist-assessed real-world data and the global spontaneous reporting system tell the same story about which skin toxicities matter most.

But the pharmacovigilance analysis also surfaced something the clinical cohort alone did not emphasize: a preliminary signal for cutaneous infections. Skin infections appeared among the reported events at a rate suggesting a possible association with the drug, yet the signal did not consistently meet the statistical threshold for significance across the analyses. The authors are careful not to overclaim. Spontaneous reporting databases are subject to well-known biases, including reporting bias, the notoriety effect in which newly publicized events get reported more often, and the absence of a denominator, since spontaneous systems rarely capture how many patients actually took the drug. Still, the biological plausibility is worth taking seriously. A chemotherapy payload delivered to keratinocytes can compromise the epidermal barrier, and a breached barrier is an invitation to bacterial, viral, and fungal pathogens. If the signal is real, it would represent a clinically distinct category of toxicity, one that is infectious rather than merely inflammatory, and it would argue for proactive skin care and early dermatologic consultation during treatment.

The timing of this work is not accidental. Sacituzumab govitecan is no longer a niche agent confined to heavily pretreated patients. Following positive phase 3 trials including TROPiCS-02 and EVER-132-002, and more recent evidence supporting its use in previously untreated advanced triple-negative breast cancer, the drug is moving earlier in treatment algorithms and reaching far larger patient populations. Perhaps more consequentially for the skin, it is entering combination regimens, including pairing with the immunotherapy pembrolizumab in triple-negative disease and in metastatic urothelial cancer. Combination therapy changes the toxicity calculus fundamentally: dermatologic events that are individually mild can compound, and immune checkpoint inhibitors bring their own rash and immune-mediated skin toxicities that can overlap or interact with those of an antibody–drug conjugate. The study’s authors explicitly flag this shift, arguing that structured dermatologic monitoring and prospective characterization of skin events are essential before combination regimens become routine practice.

There is also a quality-of-life dimension that the severity grading numbers understate. Recent reviews of dermatologic adverse events in oncology have emphasized that even grade 1 and 2 toxicities, alopecia chief among them, can profoundly affect body image, social functioning, and treatment adherence, particularly in a disease that disproportionately affects women. Mucositis interferes with eating and speaking; xerosis and pruritus disrupt sleep. Because these events cluster around the two-month mark of therapy, the study’s timing data offer a practical opportunity: prophylactic scalp cooling trials, early emollient regimens, and dental or oral hygiene interventions could all be timed to the period of maximal risk. The authors call for oncodermatologic management pathways precisely because the events are common enough to matter and mild enough that most patients will continue treatment through them, meaning the burden lands on supportive care rather than dose modification.

What the study cannot yet answer is mechanistic detail. The link between Trop-2 expression in keratinocytes and the observed toxicity spectrum remains an inference rather than a demonstrated pathway, and the retrospective design of the clinical cohort means that some milder events may have gone unrecorded in charts not oriented toward dermatologic detail. The authors themselves note that prospective studies with standardized dermatologic assessment would be the natural next step, ideally embedded within the ongoing combination trials that are reshaping the drug’s use. For now, the practical takeaway for clinicians is concrete: expect hair loss in a large fraction of patients, watch for stomatitis, itching, dryness, and rash beginning around eight weeks of therapy, reassure patients that severe skin toxicity is rare, and keep an open mind about cutaneous infections until the pharmacovigilance signal is either confirmed or refuted. For patients, the message is that the skin side effects of one of breast cancer’s most powerful modern drugs are, in the overwhelming majority of cases, an inconvenience to be managed rather than a reason to stop.

Subject of Research: Dermatologic adverse events associated with the antibody–drug conjugate sacituzumab govitecan in metastatic breast cancer

Article Title: Dermatologic adverse events associated with Sacituzumab Govitecan: an international retrospective study from the EADV Task Force “Dermatology for Cancer Patients” and pharmacovigilance analysis

Article References: Koumprentziotis, I.-A., Cawley, A., Ewig, E., Gérard, A. O., Labat, M., Kamińska-Winciorek, G., Kubeczko, M., Rapparini, L., Starace, M., Grafanaki, K., Kamaratou, M., Mavroudis, D., Katoulis, A., Nikolaou, V., Heelan, K., & Koumaki, D. (2026). Dermatologic adverse events associated with Sacituzumab Govitecan: an international retrospective study from the EADV Task Force “Dermatology for Cancer Patients” and pharmacovigilance analysis. Breast Cancer Research and Treatment, 219(3), Article 24. https://doi.org/10.1007/s10549-026-08090-5

Image Credits: AI Generated

DOI: 10.1007/s10549-026-08090-5

Keywords: sacituzumab govitecan, antibody-drug conjugate, breast cancer, dermatologic adverse events, alopecia, pharmacovigilance, VigiBase, oncodermatology, Trop-2, stomatitis, cutaneous infections, triple-negative breast cancer