Open research questions in Pharmacovigilance and Adverse Drug Reactions

What the literature leaves open

• SafeRx has not undergone prospective validation in real-world clinical settings, and its impact on medication-error reduction, alert acceptance and override rates, clinical workflow efficiency, prescribing behavior, pharmacist interventions, and patient outcomes therefore remains to be determined.

  SafeRx: A Canonical Pharmaceutical Knowledge Integration Framework for Multimodal Medication Safety · 2026 · DOI

• While TM algorithms for detecting ADRs in free-text can enhance identification, they cannot fully address this challenge. Efforts should focus on improving ADR registration, wherein electronic reminders are in accordance with the “five rights” can improve the registration. One potential solution involves integrating rule-based approaches with text mining.

  Portability of a text mining algorithm for detecting adverse drug reactions in electronic health records across diverse patient groups in two Dutch hospitals · 2026 · DOI

• Third, insufficient data were available to perform subgroup analyses based on key patient characteristics, such as HIV status, primary versus secondary prevention, or the presence of heart failure, thereby limiting the generalizability of the findings to these populations.

  Risk of hyperglycemia with different statins by type and dose: a network meta-analysis and real-world pharmacovigilance study · 2026 · DOI

• Although the association persisted in the Western Pacific–restricted analysis, differential regional awareness or coding of ICI-related cholangitis cannot be excluded, and generalizability to regions with limited vonoprazan exposure remains uncertain. Moreover, prior pharmacovigilance evidence on vonoprazan-associated cholangitis is lacking, supporting the hypothesis-generating nature of this finding.

  Vonoprazan is associated with a phenotype-specific increase in cholangitis reporting in immune checkpoint inhibitor-treated patients: a VigiBase pharmacovigilance study · 2026 · DOI

• These clinical and therefore be This study has several limitations. First, both FAERS and VigiAccess are spontaneous reporting systems and are subject to underreporting, selective reporting, missing information, and reporting stimulation effects (Sun et al., 2026).

  Real-world pharmacovigilance analysis and cross-database consistency assessment of resmetirom-related adverse events using FAERS and VigiAccess · 2026 · DOI

• However, some adverse reactions have been recorded in the long term, and the potential pharmacokinetic interaction mechanisms between NK-1 RAs and 5-HT3 RAs remain unclear.

  Adverse Event Reporting Patterns Associated with Concomitant Use of 5-HT3 and NK-1 Receptor Antagonists: A Large-Scale Spontaneous-Reporting Analysis · 2026 · DOI

• Dose interruption or reduction should be considered if platelet count drops below 75 × 109/L, in line with previous HDAC inhibitor guidelines. Lipid profiles should be monitored periodically, as hypertriglyceridemia was the strongest signal by effect magnitude.

  A disproportionality analysis of adverse event reports for givinostat in the FDA adverse event reporting system (FAERS) database · 2026 · DOI

• Third, further research is warranted to identify the mechanisms that contribute to the observed age and sex-dependent patterns of reported with LEV psychiatric adverse events.

  Characterization of Psychiatric Adverse Events Reported with Levetiracetam in the FDA Adverse Event Reporting System (FAERS) · 2026 · DOI

• Pneumonia warrants attention throughout BTK inhibitor treatment, particularly in patients with relapsed/refractory disease, prior intensive treatment, corticosteroid exposure, cytopenias, hypogammaglobulinemia, or other markers of immune compromise.

  Respiratory adverse-event signals of four Bruton tyrosine kinase inhibitors: cross-database replication and temporal characterization in FAERS and JADER · 2026 · DOI

• Several limitations of this study should be acknowledged. This introduces inherent biases, including underreporting, stimulated reporting, inconsistent data quality, and incomplete clinical information, all of which preclude the calculation of true incidence rates and limit causal inference (31).

  Reported adverse events following monovalent varicella vaccination in children aged 1–12 years: a VAERS disproportionality analysis, 1995-2026 · 2026 · DOI

• While prior studies have employed spontaneous reporting databases and identified over 100 novel adverse events associated with lumateperone, the differences in these adverse events across subgroups remain unclear.

  Heterogeneity in adverse events associated with lumateperone: a study on potential subgroup-specific differences · 2026 · DOI

• Although we validated signals using DDI resources and literature-based evidence, the available clinical evidence is limited and subject to significant inconsistencies.

  Detection of Clinically Significant Drug-Drug Interactions in Fatal Torsades de Pointes: Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System · 2025 · DOI

• Finally, an evaluation of the already developed AI models in external data is difficult because of code unavailability and a lack of data access. Furthermore, XAI methods and causal ML and causal deep learning are not investigated in depth.

  Applying AI to Structured Real-World Data for Pharmacovigilance Purposes: Scoping Review · 2024 · DOI

• Future research should explore integration with blockchain-based traceability platforms, real-time labelling systems, and federated learning architectures that preserve patient privacy while enabling multinational collaboration.

  AI-Enabled Surveillance and Modelling for Counterfeit Botulinum Toxin A: Risk Projection, Patient Safety, and Systemic Reform of Pharmacovigilance · 2026 · DOI

• The potential diabetogenic effects of statins remain controversial, particularly with respect to differences across statin types and doses.

  Risk of hyperglycemia with different statins by type and dose: a network meta-analysis and real-world pharmacovigilance study · 2026 · DOI

• Future longitudinal studies incorporating causally informed analytical approaches and complementary real-world data are warranted to validate these findings.

  Machine learning–driven pharmacovigilance of antidiabetic drugs: comparative reporting patterns and classification of serious adverse events · 2026 · DOI

• Two NRT-related ICSRs met the seriousness criterion of death, although their causal relationship with NRT remains uncertain.

  Adverse Event Reporting Patterns of Tobacco Cessation Medications in Korea: A Disproportionality Analysis · 2026 · DOI

• Further multicentric studies are warranted to better characterize the contribution of French PVCs to patient management and to evaluate their potential impact on clinical outcomes and medication safety.

  Clinical impact of a drug information service provided by a pharmacovigilance centre in a French University Hospital · 2026 · DOI

• Some of these differences may reflect underlying disease characteristics or prescribing patterns rather than drug-specific effects, and therefore caution is warranted in interpretation.

  Sex-Specific Safety Signals of Trelegy Ellipta: A FAERS Pharmacovigilance Analysis · 2025 · DOI

• Third, prescription patterns could not be assessed. Because the number of patients exposed to Trelegy Ellipta is unknown, incidence rates could not be calculated, and findings are limited to reporting proportions rather than absolute risks.

  Sex-Specific Safety Signals of Trelegy Ellipta: A FAERS Pharmacovigilance Analysis · 2025 · DOI

• Future studies should focus on improving the performance of transformer models by investigating other strategies, exploring ensemble methods, refining the classification prompt for the ChatGPT models, or incorporating different forms of data augmentation.

  Using Large Language Models to Detect and Understand Drug Discontinuation Events in Web-Based Forums: Development and Validation Study · 2024 · DOI

• Further prospective studies incorporating detailed clinical and treatment information are warranted to validate these observations.

  Safety profiles of calcineurin inhibitor-related infections in the pediatric population: a real-world pharmacovigilance analysis · 2026 · DOI

• Because explicit disease stage was sparsely recorded and treatment line could not be reliably reconstructed from FAERS, residual confounding by advanced disease status and prior treatment cannot be excluded.

  Hepatobiliary adverse-event reporting patterns for endocrine therapies in breast cancer: a pharmacovigilance study based on FAERS and VigiAccess · 2026 · DOI

• Although case numbers were low for most investigated diseases, a safety signal of progressive multifocal leukoencephalopathy (PML) could be replicated for natalizumab‐switcher…

  Replicating Safety Signals for Natalizumab Treatment in Multiple Sclerosis Patients Using German Administrative Health Insurance Claims Data · 2026 · DOI

• Second, confounding by indication, underlying disease severity, and concomitant immunosuppression represents a major limitation of the present study.

  Multi-database pharmacovigilance identifies disproportionate reporting of hepatobiliary events with avacopan: an integrative study with network pharmacology and interpretable machine learning · 2026 · DOI

Most-cited papers in Pharmacovigilance and Adverse Drug Reactions

• Incidence of Adverse Drug Reactions in Hospitalized Patients · JAMA · 1998 · 3,521 citations
• Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group · JAMA · 1995 · 2,952 citations
• Incidence of Adverse Drug Events and Potential Adverse Drug Events · JAMA · 1995 · 2,881 citations
• Systems analysis of adverse drug events. ADE Prevention Study Group · JAMA · 1995 · 1,945 citations
• The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group · JAMA · 1997 · 1,676 citations
• Systems Analysis of Adverse Drug Events · JAMA · 1995 · 1,675 citations
• Under-Reporting of Adverse Drug Reactions · Drug Safety · 2006 · 1,512 citations
• The Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada · Canadian Medical Association Journal · 2004 · 1,422 citations
• Bayesian Data Mining in Large Frequency Tables, with an Application to the FDA Spontaneous Reporting System · The American Statistician · 1999 · 919 citations
• Systematic Overview of Warfarin and Its Drug and Food Interactions · Archives of Internal Medicine · 2005 · 893 citations

Most recent work

• A disproportionality analysis of adverse events associated with omadacycline based on the FDA adverse event reporting system database · Journal of Antimicrobial Chemotherapy · 2026
• VigiBase: Resource Profile Update with a Summary of Global Patterns and Trends in Adverse Event Reports for Medicines and Vaccines · Drug Safety · 2026
• Machine learning models for drug-drug interaction prediction from computational discovery to clinical application · npj Digital Medicine · 2026
• Prevalence of Halogens in 2025 FDA-Approved Drugs: Highlight on Suzetrigine, the First Nonopioid Painkiller in Decades · Journal of Medicinal Chemistry · 2026
• Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review · Clinical Nutrition · 2026
• A Comparative Analysis of Fatal Outcomes in 5,370 Geriatric Versus 12,254 Nongeriatric Adult Patients: A Clozapine Study in VigiBase · American Journal of Geriatric Psychiatry · 2026
• Drug-induced male infertility: a real-world study using FAERS and EudraVigilance databases · Frontiers in Pharmacology · 2026
• Not All GLP‐1 Receptor Agonists Are Alike: Real‐World Evidence of Differential Endocrine and Dermatologic Safety · Diabetes/Metabolism Research and Reviews · 2026
• Critical Appraisal of Artificial Intelligence for Rare-Event Recognition: Principles and Pharmacovigilance Case Studies · Drug Safety · 2026
• Post-marketing safety signals of four JAK inhibitors for alopecia areata: an indication-restricted FAERS pharmacovigilance study · Journal of Dermatological Treatment · 2026

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