The investigators used disproportionality analysis to assess whether skin cancer appeared more often than expected among reports involving particular medicines. This approach generated reporting odds ratios (RORs) and information components (ICs) from the spontaneous-reporting data. Risankizumab had the strongest measured signal, with an ROR of 8.01, a 95% confidence interval of 7.62–8.42 and an IC025 of 2.88. Tildrakizumab had an ROR of 5.81, with a 95% confidence interval of 4.13–8.19 and an IC025 of 1.84. Ustekinumab had an ROR of 5.53, with a 95% confidence interval of 5.23–5.85 and an IC025 of 2.35. These measures quantify disproportionate reporting within FAERS; they do not establish that the medicines caused skin cancer or show the magnitude of any absolute increase in incidence.

Subgroup analyses indicated that the reporting association was more pronounced among older patients, particularly those older than 75 years. The researchers also performed time-to-onset analysis and Weibull modelling to examine reporting patterns after treatment initiation. The modelling identified a “wear-out” failure pattern for ustekinumab and risankizumab, indicating that the frequency of reports increased over time in the dataset. This pattern describes when reports accumulated; it does not demonstrate that cancer risk itself rises with longer treatment. Additional analyses of interactions with co-medications did not identify significant synergistic reporting signals for skin cancer.

The findings are best understood as signal detection from a spontaneous-reporting database rather than a comparison of cancer incidence among treated and untreated groups. The study’s population comprised individual safety reports entered into FAERS, and its results concern reporting associations for IL-12/23, IL-23 and IL-17 inhibitors during the specified period. The authors concluded that disproportionate skin-cancer reporting warrants further prospective investigation to establish its clinical significance, particularly for risankizumab and ustekinumab. Their results do not demonstrate that the medicines cause skin cancer, quantify absolute risk or establish that the observed reporting pattern reflects a change in the incidence of skin cancer. The findings also do not support treating the weaker IL-17 inhibitor signals as causally established, especially after they disappeared in the psoriasis-restricted sensitivity analysis.

Subject of Research: FAERS disproportionality analysis of skin-cancer reporting involving IL-12/23, IL-23 and IL-17 inhibitors.

Article Title: Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database

Article References: Jiang, X., Huang, Y., Xie, M., Peng, L., Xu, M., Qi, Z., Wang, G., & Pu, X. (2026). Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database. Frontiers in Pharmacology, 17, Article 1944368. https://doi.org/10.3389/fphar.2026.1944368

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1944368

Keywords: FAERS, pharmacovigilance, skin cancer, disproportionality analysis, IL-23 inhibitors, IL-17 inhibitors, risankizumab, ustekinumab, tildrakizumab, adverse-event reporting, Potential, association

The analysis drew on 24,117,949 adverse-event reports available in FAERS during the study period. Records were identified under the generic names givinostat and givinostat hydrochloride and the trade name Duvyzat, and only reports assigning givinostat the primary-suspect role were included. Investigators removed duplicate records using the database case identifier and coded events with Medical Dictionary for Regulatory Activities preferred terms. The resulting series was highly concentrated geographically, with 306 reports, or 95.3%, coming from the United States. Patients were predominantly male: 308 of 321 cases, or 96.0%, were male, while one was female and 12 had missing sex. Ages were broadly distributed, but 72 reports, or 22.4%, lacked age information, and outcome data were absent in 257 cases, or 80.1%. These features constrain subgroup analysis and make the distinction between a genuinely non-serious event and an event for which no serious outcome was documented especially important.

At the system-organ-class level, investigations had the strongest reporting-odds signal, with a reporting odds ratio of 5.54 and a 95% confidence interval of 4.71 to 6.53. Gastrointestinal disorders followed with a reporting odds ratio of 4.09, with a 95% confidence interval of 3.48 to 4.80, while blood and lymphatic system disorders had a ratio of 3.43, with a 95% confidence interval of 2.51 to 4.71. The Bayesian information components for these three categories had lower 95% confidence bounds above zero, meeting the study’s signal threshold. Investigators also applied the proportional reporting ratio, Bayesian Confidence Propagation Neural Network and Multi-item Gamma Poisson Shrinker. A preferred term was considered a signal if it met the criteria of at least three of the four methods, allowing signal detection to depend on consistency across frequentist and Bayesian approaches. Twenty preferred-term signals were identified by all four methods, including platelet count decreased, thrombocytopenia, diarrhoea, nausea and increased blood triglycerides. These statistics describe reporting disproportionality relative to the FAERS background; they are not incidence rates or direct measures of a drug’s clinical risk.

At the preferred-term level, blood triglycerides increased produced the strongest signal by reporting odds ratio: 341.3, with a 95% confidence interval of 253.18 to 460.10. It appeared in 47 reports, representing 14.64% of the givinostat series. Platelet count decreased was the most frequently reported term, occurring in 96 reports, or 29.91%, and had a reporting odds ratio of 91.7, with a 95% confidence interval of 73.97 to 113.68. Diarrhoea occurred in 62 reports, or 19.31%, with a reporting odds ratio of 8.29 and a 95% confidence interval of 6.39 to 10.75. Abdominal discomfort appeared in 31 reports, or 9.66%, and thrombocytopenia in 30, or 9.35%. Nausea and vomiting were reported in 27 and 23 cases, respectively. The contrast between frequency and disproportionality was notable: decreased platelet count was the most common reported event, whereas increased triglycerides had the largest relative reporting signal. Product dose omission issue and off-label use were also identified but excluded as operational or recording-related signals rather than pharmacological safety events.

The investigators analyzed platelet count decreased and thrombocytopenia separately because MedDRA distinguishes a reduced platelet-count laboratory finding, categorized under investigations, from a clinician-coded diagnosis of thrombocytopenia, categorized under blood and lymphatic system disorders. When both terms appeared in one report, the case was retained in both term-specific analyses and the overlap was quantified; the terms were not combined into a composite endpoint. Seriousness was based solely on FAERS outcome codes for death, hospitalization, life-threatening events or other serious outcomes. Sixty-four reports, or 19.9% of the series, contained at least one such coded outcome. The other 257 reports, or 80.1%, were operationally grouped as having no documented serious outcome. They were not confirmed non-serious events, and some reports could contain more than one serious outcome, so total outcome codes can exceed the number of reports.

Unadjusted analyses suggested different seriousness patterns for laboratory and clinical platelet terms. Among the 30 reports containing thrombocytopenia, 53.33% had a documented serious outcome and 46.67% did not, whereas among the 96 reports containing platelet count decreased, 14.58% had a documented serious outcome and 85.42% did not. These are proportions within each preferred-term group, not the proportion of all serious reports in which each event occurred. Pyrexia also showed a higher documented-seriousness proportion within its own group, at 63.64%, while blood triglycerides increased had a documented-seriousness proportion of 14.89%. After a likelihood ratio analysis with Benjamini–Hochberg false-discovery-rate correction, platelet count decreased was the only preferred term that differed significantly from the overall preferred-term-entry baseline of 30.07% documented serious outcomes, with an adjusted p value of 0.024. Thrombocytopenia had an adjusted p value of 0.071, blood triglycerides increased had 0.151 and pyrexia had 0.132, meaning those nominally significant unadjusted differences did not survive correction. Their estimates remained imprecise because of the small number of reports.

Time-to-onset analysis suggested that gastrointestinal and platelet-related events could emerge at different stages after treatment began, although only 124 of the 321 reports, or 38.6%, had complete and plausible dates for calculating onset. Among non-serious diarrhoea reports, the median time to onset was 3.5 days, with an interquartile range of 0.25 to 18.25 days. Non-serious platelet count decreased had a median onset of 15.5 days, with an interquartile range of 14.25 to 32.5 days, while thrombocytopenia had a median onset of 17 days and an interquartile range of 2 to 24 days. Across evaluable adverse events, 50.79% were reported within the first 30 days. Serious platelet count decreased had a descriptive median onset of 63 days, but that group contained only four reports, compared with six non-serious reports, and the comparison was not adjusted for multiple testing. The authors therefore did not treat the timing difference as evidence that serious platelet changes consistently occur later.

Regression models did not identify age, weight or corticosteroid use as independent predictors of a documented serious outcome. The complete-case analysis included 185 reports, of which 51, or 27.6%, had a documented serious outcome. Reports involving patients aged 18 or older had a serious-outcome proportion of 35.6%, compared with 23.8% among those younger than 18, but the adjusted odds ratio was 1.64, with a 95% confidence interval of 0.79 to 3.37 and an adjusted p value of 0.182. Patients weighing more than 45 kilograms had an adjusted odds ratio of 1.21, with a 95% confidence interval of 0.60 to 2.45, while reported corticosteroid use had an adjusted odds ratio of 1.66, with a 95% confidence interval of 0.87 to 3.22. No preferred term significantly modified the reporting profile across age, weight or time-to-onset subgroups after correction. These null findings do not prove that the factors have no association: the sample was small, confidence intervals were wide and the severe missingness reduced statistical power.

In an exploratory active-comparator analysis, givinostat had a reporting odds ratio of 91.70, with a 95% confidence interval of 73.97 to 113.68, for platelet count decreased and 23.76, with a 95% confidence interval of 16.48 to 34.24, for thrombocytopenia. Vamorolone had a positive disproportionality signal for platelet count decreased, with a reporting odds ratio of 2.39 and a 95% confidence interval of 1.38 to 4.12, but not for thrombocytopenia, for which its ratio was 0.17, with a 95% confidence interval of 0.02 to 1.19. Stable reporting-odds-ratio estimates were unavailable for prednisone and deflazacort because of insufficient reports, so the analysis did not establish that givinostat had stronger platelet-related signals than either drug. Comparator results were also not head-to-head risk estimates. The exceptionally large triglyceride signal may reflect givinostat, underlying disease activity, concomitant glucocorticoid-associated metabolic effects, more intensive lipid surveillance or a combination of these factors, rather than givinostat alone.

Overall, the FAERS analysis points to platelet-related and metabolic events as the clearest reporting signals following givinostat’s launch, with platelet count decreased particularly frequent and increased blood triglycerides particularly disproportionate in the database. The adjusted seriousness result adds a nuance: a laboratory finding of decreased platelets was common but had a lower documented-seriousness proportion than the overall preferred-term-entry baseline, while clinically coded thrombocytopenia appeared more serious but did not remain significant after multiple-testing correction. Missing exposure denominators, under-reporting, stimulated reporting, incomplete outcome fields, heavy use of concomitant corticosteroids and the predominance of 2024 reports prevent the study from estimating how often these events occur or whether givinostat caused them. The authors identified platelet and lipid monitoring during early treatment as targets for structured follow-up, but the signals require validation in registries or electronic health records with more complete exposure, laboratory and clinical-outcome data before they can be treated as definitive safety estimates.

Subject of Research: Retrospective pharmacovigilance analysis of givinostat adverse-event reports for Duchenne muscular dystrophy

Article Title: A disproportionality analysis of adverse event reports for givinostat in the FDA adverse event reporting system (FAERS) database

Article References: Chen, L., Zhang, H., Wang, Y., Feng, X., Hou, Y., & Su, Q. (2026). A disproportionality analysis of adverse event reports for givinostat in the FDA adverse event reporting system (FAERS) database. Frontiers in Pharmacology, 17, Article 1954821. https://doi.org/10.3389/fphar.2026.1954821

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1954821

Keywords: givinostat, Duchenne muscular dystrophy, FAERS, pharmacovigilance, thrombocytopenia, platelet count decreased, hypertriglyceridemia, adverse-event reporting, disproportionality analysis, drug safety, time to onset, disproportionality

Under US regulations, medical device manufacturers are required to report malfunctions and adverse events to the FDA within 30 days. These reports feed into the MAUDE database, which regulators, clinicians, researchers, and the public rely on to identify potential safety signals that may warrant product recalls, label changes, or other corrective actions. For the system to function as intended, the reports must be complete and accurate. Yet earlier programs, most notably the Alternative Summary Reporting program, allowed manufacturers to submit millions of adverse events as bulk summaries rather than as individual case reports, a policy framed as a way to reduce the burden on industry. The FDA ended that program in 2019 amid concerns that it was masking safety signals, but similar summary reporting exemptions remain in use today, and until now their accuracy, completeness, and compliance with FDA rules were largely unknown.

To close that gap, researchers analyzed all adverse event summary reports submitted to MAUDE between July 2019 and June 2025. They looked for four specific types of failure: incomplete identification of the device or use problem involved, undercounting of the number of adverse events, failure to correctly identify the submission as a summary report, and delays in reporting serious adverse events beyond the regulatory deadline. The dataset they examined was substantial. During the six-year study period, 6,308 summary reports were submitted to the FDA, containing a total of 159,503 adverse events. The majority of these events involved high-risk devices, the very category of products where timely safety intelligence matters most.

The results paint a troubling picture of a reporting pipeline riddled with defects. Fifty-seven percent of the summary reports identified no device or use problem at all, leaving regulators without a clear indication of what went wrong. Thirty-eight percent contained insufficient information to evaluate the events described. Eleven percent were incorrectly identified as non-summary reports, meaning they would not be flagged or processed as aggregated submissions. Seven percent incorrectly listed only one event in the number of events field, even when multiple adverse events were involved. Perhaps most alarmingly, 55 percent of the reports exceeded the FDA’s 30-day reporting deadline, meaning that more than half of the aggregated safety information arrived late, in some cases long after the window in which it could have contributed to a rapid regulatory response.

The scale of the problem is growing rather than shrinking. The researchers note that the number of summary reports submitted to the FDA, and the number of adverse events contained within them, more than doubled between 2020 and 2024. That trajectory suggests manufacturers are increasingly relying on bulk summary mechanisms to discharge their reporting obligations, even as the quality of those submissions falls short of the standards the agency itself has set. In a passive reporting system that depends entirely on the diligence of the regulated industry, systematic gaps in data quality translate directly into blind spots in national device surveillance, potentially delaying the recognition of hazards affecting widely implanted or widely used products.

The authors of the study are candid about the limitations inherent in their analysis. Passive adverse event reporting has well-known weaknesses, including incomplete ascertainment of events in the real world and the absence of a denominator of device use against which event rates can be calculated. The researchers also lacked access to publicly available information on the specific requirements governing the summary reporting exemptions, which constrained their ability to assess compliance against detailed regulatory criteria. Even so, they argue that identifying and correcting the flaws documented in the study is vital, particularly given the accelerating volume of summary reporting. Immediate improvements, they write, are needed to better protect patient safety and adhere to the transparency principles outlined by the FDA, adding that making serious adverse event reports fully visible and accessible is critical to patient safety.

The study’s publication was accompanied by a linked editorial from Koji Todaka of Kyushu University Hospital in Japan, who frames the findings as a challenge to the fundamental purpose of the reporting system. The MAUDE database exists to support public scrutiny of medical device safety, and reports that are incomplete, mislabeled, or late undermine that mission, he argues. When the public cannot see an accurate and timely account of adverse events associated with the devices used in their care, trust in postmarket surveillance erodes, and the evidence base for clinical decision-making weakens accordingly.

Todaka proposes a set of reforms aimed at restoring confidence in the system. Regulators, he suggests, should require accurate and timely summary reporting, standardized device identification, and clear links between adverse event reports and device registries. Standardized identification is particularly consequential, because ambiguous device problem descriptions and inconsistent device identifiers make it difficult to aggregate reports across manufacturers and time periods, which is precisely the kind of aggregation needed to detect a safety signal. He also recommends that researchers integrate spontaneous reports, registry data, and linked healthcare records rather than treating any single data source as definitive, reflecting a broader consensus that passive reporting alone cannot carry the full weight of postmarket safety surveillance.

Change may be on the horizon within the FDA itself. The agency is currently transitioning to a new Adverse Event Monitoring System, or AEMS, designed to consolidate existing reporting systems and publish adverse event reports in real time. If the new platform enforces structured data entry, validates event counts, timestamps submissions against the 30-day requirement, and makes serious adverse event reports immediately visible to the public, it could address many of the deficiencies documented in the BMJ analysis. The transition also presents an opportunity to revisit the summary reporting exemptions themselves, tightening the conditions under which bulk submissions are permitted and requiring manufacturers to supply the device and problem information that more than half of current reports omit.

The stakes of this administrative infrastructure are far from abstract. High-risk devices, including implants, cardiac devices, and surgical equipment, are used in millions of patients, and a delayed or obscured safety signal can mean continued exposure to a malfunctioning product for months or years. The BMJ study demonstrates that the mechanisms meant to catch those signals are, in their current form, leaking information at every stage: at submission, in classification, in event counts, and in timing. As the researchers and the accompanying editorial both emphasize, transparency builds trust and evidence improves safety, and both are essential to effective postmarket surveillance and safer medical devices. Whether the FDA’s new monitoring system, combined with stricter oversight of summary reporting, can close the gaps identified in this study will be a defining test of the next chapter of medical device regulation in the United States.

Subject of Research: Accuracy, completeness, and timeliness of summary adverse event reporting to the FDA MAUDE medical device safety database

Article Title: Medical device adverse event reports are often incomplete, inaccurate, and delayed

Article References: Medical device adverse event reports are often incomplete, inaccurate, and delayed. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: medical devices, FDA, MAUDE database, adverse event reporting, postmarket surveillance, patient safety, summary reporting exemptions, BMJ, device regulation, safety signals, transparency, regulatory compliance

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