Open research questions in Pharmacovigilance and Adverse Drug Reactions
61 unresolved questions extracted from the limitations and future-work sections of 478 Pharmacovigilance and Adverse Drug Reactions papers in our library. Each links back to the study that raised it.
What the literature leaves open
Cytokine release syndrome (CRS) is a potentially life-threatening systemic inflammatory reaction associated with immunotherapies and other medications, yet its risk profile across marketed drugs remains poorly characterized.
Real-world risk assessment of drug-induced cytokine release syndrome: Analysis of the Food and Drug Administration Adverse Event Reporting System · 2026 · DOIAlthough AI and related technologies have been proposed to support causality assessment, limited research has examined how these methods are used, their information and quality requirements, or how associated risks are addressed.
The applicability of large language models (LLMs) to formal World Health Organization–Uppsala Monitoring Centre (WHO-UMC) drug–adverse event causality assessment has not been well established.
Large Language Models for World Health Organization–Uppsala Monitoring Centre Drug–Adverse Event Causality Assessment Using Food and Drug Administration Adverse Event Reporting System Cases: Comparative Performance Study · 2026 · DOIAjmal, C. S., et al. "Innovative approaches in regulatory affairs: leveraging artificial intelligence and machine learning for efficient compliance and decision-making." The AAPS Journal 27.1 (2025): 22. 63. Ahire, Yogesh S., et al. "Advanced applications of artificial in pharmacovigilance: Current trends and future perspectives." J Pharm Res 23.1 (2024): 23- 33. intelligence 64. Salas, Maribel, et al. "The use of artificial intelligence in pharmacovigilance: a systematic review of the literature." Pharmaceutical medicine 36.5 (2022): 295-306. 65. Ahire, Yogesh S., et al. "Advanced applications of artificial in pharmacovigilance: Current trends and future perspectives." J Pharm Res 23.1 (2024): 23- 33. intelligence 66. Ahire, Yogesh S., et al. "Advanced applications of artificial in pharmacovigilance: Current trends and future perspectives." J Pharm Res 23.1 (2024): 23- 33. intelligence 67. Korade Payal, B., et al. "Pharmacovigilance: A Pillar of Modern Drug Safety." Asian Journal of Pharmaceutical Research and Development 13.5 (2025): 60-68. 68. Ahire, Yogesh S., et al. "Advanced applications of artificial in pharmacovigilance: Current trends and future perspectives." J Pharm Res 23.1 (2024): 23- 33. intelligence How to cite this article: Arshad et al. (2026). Next-Generation Pharmacovigilance: The Role of AI and Machine Learning in Detecting and Managing Drug Risks. Interdisciplinary Journal of the African Alliance for Research, Advocacy and Innovation. Vol 2, Issue 2. April-June. https://doi.org/10.64261/x8f2hr74. Interdisciplinary Journal of the African Alliance For Research, Advocacy & Innovation ISSN (O): 3093-4664 69. Sardella, Marco, and Lucia Costanzo. "The 7th European Pharmacovigilance Congress: speaker abstracts." 70. Ahire, Yogesh S., et al. "Advanced applications of artificial in pharmacovigilance: Current trends and future perspectives." J Pharm Res 23.1 (2024): 23- 33. intelligence 71. Beninger, Paul. "Signal management in pharmacovigilance: a review of activities and case studies." Clinical therapeutics 42.6 (2020): 1110-1129. 72. Watson, Richard T. Data management, databases and organizations. John Wiley & Sons, 2008. 73. Signal Management is the continuous review of safety-related data to identify trends or indications of the reported adverse incidents 74. Tieu, Carolyn, and Christopher D. Breder. "A critical evaluation of safety signal analysis using algorithmic standardised MedDRA queries." Drug safety 41.12 (2018): 1375-1385. 75. The application of benefit-Risk Management involves the continuous assessment of the positive effects of a drug against the risks 76. Butler, Dianne, et al. "Regulatory experience of handling risk management plans (RMPs) for medicinal products in the EU." Expert Opinion on Drug Safety 20.7 (2021): 815-826 77. WILSON, LAUREN.
Next-Generation Pharmacovigilance: The Role of AI and Machine Learning in Detecting and Managing Drug Risks · 2026 · DOIHow to cite this article: Arshad et al. (2026). Next-Generation Pharmacovigilance: The Role of AI and Machine Learning in Detecting and Managing Drug Risks. Interdisciplinary Journal of the African Alliance for Research, Advocacy and Innovation. Vol 2, Issue 2. April-June. https://doi.org/10.64261/x8f2hr74. Interdisciplinary Journal of the African Alliance For Research, Advocacy & Innovation ISSN (O) : 3093-4664 With the further development of data ecosystems, analytics, and regulatory standards, the future of AI and ML in pharmacovigilance is going to become more advanced. Further studies ought to be carried out to come up with explainable and transparent AI models to increase trust, interpretability, and regulatory acceptance. Interpretable deep learning and causal inference are the methods that may help to overcome the divide between algorithmic predictions and clinical decision-making. The other important direction is the development of high quality and standardized as well as real world data that can be used in the training of the model on a variety of population. Electronic health records, global safety databases, and social media platforms will be interoperable, which will facilitate a more thorough safety surveillance. It requires shared information systems between regulatory agencies, pharmaceutical firms, and health care systems to facilitate this. Multimodal AI-based methods that combine clinical text, genomics, wearable device data, and imaging to support individual risk prediction of ADRs will also be the future of pharmacovigilance. Moreover, AI systems with the ability to detect signals in real-time and automatically screen cases can considerably decrease the delays in reporting and the load of work. The regulatory agencies need to keep on streamlining rules regarding validation, auditing, and lifecycle monitoring of AI systems. Safe adoption will be reliant on the introduction of human-AI collaboration models, like those in which AI assists, but not rules out the expertise. Ethical aspects, such as data privacy, reduction of bias, and accountability, will be the primary points of focus. In general, the future environment will cease to be reactive in terms of ADR reporting, that is, become proactive and predictive (as well as patient-centered) in terms of drug safety through the power of robust, transparent, and ethically based AI technologies.
Next-Generation Pharmacovigilance: The Role of AI and Machine Learning in Detecting and Managing Drug Risks · 2026 · DOIWhile FAERS data cannot establish causality, these real-world insights contribute to a broader understanding of dacomi- tinib's safety profile, particularly regarding drug-drug inter- actions and underrecognized organ system involvement, and underscore the importance of ongoing pharmacovigilance.
A real-world pharmacovigilance study of dacomitinib based on FDA adverse event reporting system (FAERS) database · 2026 · DOIApplying a TMP‐SMX ARDS phenotype to a national health care database paired with clinical review of candidate cases may be an effective approach to identify underrecognized ADRs.
Leveraging Administrative Health Data to Capture Rare Adverse Drug Reactions: Identifying Pediatric Patients With Trimethoprim‐Sulfamethoxazole Acute Respiratory Distress Syndrome · 2026 · DOIWhile large language models (LLMs) can interpret such unstructured data more effectively than traditional natural language processing methods, few studies have systematically categorized reasons for discontinuation or identified whether the decision was initiated by the patient or the clinician, especially in low-resource languages such as Estonian.
Extracting and Classifying Drug Discontinuations From Estonian Electronic Health Records: Development and Validation Study · 2026 · DOIThis study represents our second investigation in Italy focusing on O-AEs using post-marketing data from the RNF, specifically from the regions of Piedmont, Campania, and Sicily. Our previous analysis, which covered the 2019– 2021 period, was significantly affected by the high volume of ICSRs related to COVID-19 vaccines, largely due to the mass vaccination campaign active during that time. This constituted a major limitation, as it potentially skewed the overall distribution and characterization of reported O-AEs. In the present study, this limitation was overcome by ana- lyzing a more recent time frame (2022–2024), in which the impact of pandemic-related reporting was considerably reduced. As in our previous study, the decision to focus on this specific safety concern stemmed from the need to explore in greater depth the real-world data on O-AEs. Investigat- ing O-AEs within a post-marketing surveillance framework offers a valuable perspective to promote more rational drug use, guide clinical behavior, and ultimately enhance patient safety. This focus on real-life pharmacovigilance data remains one of the key strengths of our research. Moreover, several study limitations should be taken into consideration. The results from our study are subject to typical pharmacovigilance biases, including under- reporting [61]. Additionally, the RNF does not routinely capture exposure denominators, such as the number of patients treated with specific medications at the regional level. Since the present project was specifically designed to rely exclusively on RNF data, crude reporting rates or incidence estimates could not be calculated. Therefore, our analyses were limited to descriptive and disproportionality approaches. Furthermore, as already discussed in our previ- ous study, stimulated reporting may have influenced report- ing patterns, particularly during the COVID-19 vaccination campaign, when heightened public awareness and media attention likely led to a temporary overrepresentation of vaccine-related reports [4].
Italian regional data and oropharyngeal adverse events to drugs and vaccines: insights from a 3-year spontaneous reporting (2022–2024) · 2026 · DOIThe robustness of this investigation is grounded in several key methodological advantages, beginning with the implementation of a regulatory-grade gold standard for performance comparison. By utilizing high-quality causality assessments conducted by expert human assessors, specifically a senior medical doctor from a pharmaceutical company and a specialist pharmacist, this study ensured that the reference standard met rigorous industry and regulatory expectations. Furthermore, the evaluation was performed on a heterogeneous dataset of 150 real-world ICSRs rather than focusing on a single drug class. This diverse sample spanned several distinct categories, including newly approved drugs, gene and cell therapies, commonly prescribed medications, and clinically confirmed vaccine reports from the VAERS database. A key methodological strength is the complete concordance between the two human expert assessors across all 150 ICSRs and both algorithms.
Biomedical Large Language Models and Prompt Engineering for Causality Assessment of Individual Case Safety Reports in Pharmacovigilance · 2026 · DOIVancomycin HSRs represent a broad clinical spectrum ranging from immediate to delayed hypersensitivity syndromes. Most immediate reactions are now recognized as non—IgE-mediated, potentially primarily driven by MRGPRX2-dependent mast cell activation rather than classical IgE-mediated allergy. At the other end of the clinical spectrum, the HLA-A*32:01 allele has emerged as a key genetic risk factor for vancomycin-induced DRESS. Moving forward, establishing standardized diagnostic methods and reproducible testing protocols is essential to distinguish VIR from IgE-mediated hypersensitivity. Combining mechanistic phenotyping with genomic and cell-based diagnostics, informed by clinical, pharmacologic, and molecular data, will refine diagnosis and enable individualized patient management. Embedding clinical decision support tools within EHRs can improve recognition, documentation, and delabeling, whereas addressing disparities in access to allergy evaluation remains critical for equitable these efforts will strengthen antibiotic stewardship, prevent unnecessary vancomycin avoidance, and advance safer, mechanism-based care for patients with suspected vancomycin hypersensitivity. implementation. Collectively, In patients labeled as being vancomycin allergic, clinicians are often compelled to use alternative agents for MRSA and other resistant gram-positive infections (Table III).94-96 Although several options exist, each carries important limitations. Linezolid is bacteriostatic and may cause myelosuppression; daptomycin is ineffective for pneumonia; ceftaroline and ceftobiprole raise concerns about β-lactam cross-reactivity; and tigecycline has low serum levels, gastrointestinal intolerance, and an associated mortality signal in bloodstream infections.95-98 In addition to these drawbacks, most alternatives are substantially more expensive. Although fidaxomicin is a first-line option alongside oral vancomycin for C difficile colitis, its high-cost limits realworld use, leaving vancomycin as the practical standard. Mislabeling therefore restricts therapeutic options, increases health care costs, and may preclude the use of long-acting lipoglycopeptides facilitate early discharge.97 Accurate documentation and allergist-led evaluation are essential to guide testing, delabeling, and/or rechallenge when appropriate, and to ensure patients safely receive effective first-line therapies. such as dalbavancin that Electronic health record documentation and allergy reconciliation Accurate EHR documentation of vancomycin HSRs is critical to patient safety and antibiotic stewardship. Current data reveal substantial inconsistencies. Many reactions are misclassified under generic vancomycin allergy DALs.20 Such inaccuracies disproportionately affect certain populations and lead to unnecessary drug avoidance, suboptimal antibiotic choices, and increased health care costs.
Future pharmacovigilance systems will increasingly use electronic health records, artificial intelligence, and digital reporting platforms. Community pharmacists will continue to play a vital role in these systems by ensuring safe medication use and reporting ADRs promptly. The future of Adverse Drug Reaction (ADR) monitoring is expected to evolve significantly with the advancement of pharmacovigilance systems and digital healthcare technologies. The integration of electronic health records, artificial intelligence, and big data analytics will facilitate the early detection and systematic evaluation of adverse drug reactions. These technological innovations can improve signal detection, enhance data accuracy, and enable www.wjpr.net │ Vol 15, Issue 11, 2026. │ ISO 9001: 2015 Certified Journal │ 276 Anju et al. World Journal of Pharmaceutical Research real-time monitoring of drug safety. Furthermore, global collaboration among regulatory authorities, healthcare institutions, and pharmaceutical industries will strengthen international pharmacovigilance networks and improve the sharing of drug safety information. In addition, increasing awareness and education among healthcare professionals and patients will play a vital role in improving ADR reporting in the future. The implementation of mobile applications and online reporting platforms will simplify the reporting process and encourage active participation from both healthcare providers and patients. Personalized medicine and pharmacogenomics may also help predict individual susceptibility to adverse drug reactions, thereby reducing drug-related risks. Consequently, the advancement of innovative pharmacovigilance strategies will enhance patient safety and ensure the safer utilization of therapeutic agents.
These hypothesis-generating signals suggest that immune-related AEs for NM and metabolic complications for sodium citrate warrant further investigation in controlled studies.
Original research a real-world study of adverse events of nafamostat mesylate and sodium citrate based on the world health organization-VigiAccess database · 2026 · DOIthe pharmacovigilance methodology should be considered when interpreting our findings. First, rather than establishing definitive causal relationship, disproportionality analysis can only determine statistical associations between drug exposure and AEs. Second, the FAERS, as a spontaneous reporting system, is subject to reporting limitations, inherent information. biases, and potential Third, and underlying disease progression could not be fully adjusted. Moreover, the absence of precise event onset dates in a subset of reports may impact the robustness of time-to-onset analyses and consequently interpretation of certain safety signals. including underreporting, incompleteness of case concomitant medications confounding by the accurate In conclusion, data mining of the FAERS database of demonstrates mosunetuzumab (CRS, neutropenia and injection site reactions) and potential safety the encompasses established real-world profile safety risks that FIGURE 3 Overlap of PT level safety signals identified by four disproportionality methods for mosunetuzumab in FAERS. fluctuations, which coincide with CRS manifestations, have been proposed as a potential predictive biomarker, though this association awaits confirmation in dedicated studies (Nakamura et al., 2023). We identified a range of infection-related events as high- frequency positive signals, which covered pneumonia, pleural effusion, septic shock, sepsis, and cytomegalovirus infection. Our findings align closely with the incidence and spectrum in previous studies (Sun and Romancik, 2025). reported Furthermore, two published reports have highlighted the broad clinical burden of infections: one reported a fatal event due to human herpesvirus-6 (HHV-6) infection, the other described chronic persistent parvovirus B19 infection (Samperio et al., 2025; Füreder et al., 2025). Additionally, a fatal case of pleural effusion has been reported with Epcoritamab, an alternative linked to CD20×CD3 bispecific antibody. This event was potentially epcoritamab’s contributing to local CRS (Takahata et al., 2025), but remains mechanistically unvalidated. Expert guidelines recommend infection until withholding mosunetuzumab during active in routine resolution, with uninfected patients (Crombie et al., 2024). immunoglobulin monitoring on-target activity, pleural systemic Beyond established adverse events, we identified potential safety signals across several SOCs, including cardiac and eye disorders. For cardiac events, atrial fibrillation was the only positive signal. Despite its low reported incidence in real-world cohorts, this signal warrants ongoing clinical monitoring (Sayed et al., 2024). The onset of atrial fibrillation may be mediated by CRS-driven immune pathways, though direct biological evidence remains lacking (Sayed et al., 2024; Munir et al., 2024). Uveitis was the sole ocular signal detected. Importantly, FL itself can involve the ocular adnexa, most commonly the conjunctiva, lacrimal gland, and orbit. However, direct lymphomatous infiltration of the uveal tract is extremely rare (Rasmussen et al., 2014; da Cunha et al., 2014).
Real-world safety profile of mosunetuzumab: a pharmacovigilance study based on the food and drug administration adverse event reporting system · 2026 · DOIDevanssh Mehta* Founder & Director, TRM Writer’s LLP Founder, Market Mavericks Digital OPC Pvt Ltd Modipuram, Meerut, Uttar Pradesh, India – 250110. How to cite this Article: Devanssh Mehta*. (2026). STRATEGIC EVOLUTION OF PHARMACOVIGILANCE IN THE MODERN HEALTHCARE ECOSYSTEM: A SYSTEMATIC REVIEW AND FUTURE OUTLOOK. World Journal of Advance Pharmaceutical Sciences, 3(5), 137-139.
STRATEGIC EVOLUTION OF PHARMACOVIGILANCE IN THE MODERN HEALTHCARE ECOSYSTEM: A SYSTEMATIC REVIEW AND FUTURE OUTLOOK · 2026 · DOIPredictive Pharmacovigilance AI-driven models will identification. enable proactive risk 9.2 Patient-Centric Systems Increased patient involvement in ADR reporting. 9. Lindquist, M. (2008) ‘VigiBase and global drug safety’. 10. McBride, W.G. (1961) ‘Thalidomide and congenital abnormalities’, The Lancet. 11. Sherman, R.E. et al. (2016) ‘Real-world evidence in regulatory decision making’, NEJM, 375(23): 2293–2297. 12. WHO (2023) Pharmacovigilance and Drug Safety.
STRATEGIC EVOLUTION OF PHARMACOVIGILANCE IN THE MODERN HEALTHCARE ECOSYSTEM: A SYSTEMATIC REVIEW AND FUTURE OUTLOOK · 2026 · DOIInput normalization and bounded fuzzy matching techniques are mentioned as future enhancements to strengthen ASA robustness against obfuscation in Thai healthcare advertising. The specific implementation details, fuzzy matching thresholds, and normalization algorithms for Thai language text processing require development and validation.
The paper indicates ASA will be broadened to include related regulatory domains such as cosmetics and nutritional supplements advertising. This expansion requires developing domain-specific rule sets and validating the compliance checking framework against the distinct regulatory requirements of these non-healthcare advertising categories.
The ASA framework evaluation was limited to phrase-level detection on a dataset of Thai clinic and social media advertising terminology. Future work requires expanding the obfuscation-aware rule dataset to include adversarial examples of deliberately obscured prohibited terms and testing on diverse healthcare advertising sources beyond current evaluation conditions.
The ASA rule-based detection algorithm is inherently susceptible to obfuscation techniques including Unicode variation, character substitution, and spacing manipulation in Thai healthcare advertising text. Future work must expand preprocessing techniques and develop hybrid detection approaches that incorporate obfuscation-aware rules while maintaining transparency and contextual awareness.
Whilst pharmacovigilance (PV), including the submission of individual case safety reports (ICSR) to VigiBase(®), the WHO global ICSR database, is growing in Africa, no data have been published on the growth of ICSR reporting from Africa and how the features of ICSRs from Africa compare with the rest of the world (RoW).
Adverse Drug Reaction Reporting in Africa and a Comparison of Individual Case Safety Report Characteristics Between Africa and the Rest of the World: Analyses of Spontaneous Reports in VigiBase® · 2016 · DOIHowever, given that vulnerability to publicity-stimulated reporting is a potential limitation of spontaneous reporting systems like the FAERS, the potential impact of publicity on reporting in this case remains unclear.
Introduction: Immune checkpoint inhibitors (ICIs) are frequently co-administered with glucocorticoids (GCs) in cancer treatment, yet the potential drug-drug interactions (DDIs) between these drug classes remains incompletely characterized.
Drug-Drug Interactions Between Immune Checkpoint Inhibitors and Glucocorticoids: A Real-World Pharmacovigilance Analysis · 2026 · DOIHowever, it should be acknowledged that disproportionality analysis is a hypothesis-generating or refinement approach, and further confirmatory studies are warranted to establish causal relationships.
FAERS-based pharmacovigilance study of sevoflurane-associated adverse events: A 20-year comprehensive analysis · 2026 · DOIConclusion: These findings provide critical insights into sevoflurane’s real-world safety profile, particularly revealing severe yet underrecognized risks that can inform enhanced clinical monitoring and safer anesthetic practice.
FAERS-based pharmacovigilance study of sevoflurane-associated adverse events: A 20-year comprehensive analysis · 2026 · DOI
Most-cited papers in Pharmacovigilance and Adverse Drug Reactions
- Systematic Overview of Warfarin and Its Drug and Food Interactions · Archives of Internal Medicine · 2005 · 893 citations
- Physicians' Decisions to Override Computerized Drug Alerts in Primary Care · Archives of Internal Medicine · 2003 · 381 citations
- The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration · Drug Safety · 2024 · 270 citations
- Digital Drug Safety Surveillance: Monitoring Pharmaceutical Products in Twitter · Drug Safety · 2014 · 228 citations
- The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement · Drug Safety · 2024 · 180 citations
- Disproportionality Analysis for Pharmacovigilance Signal Detection in Small Databases or Subsets: Recommendations for Limiting False-Positive Associations · Drug Safety · 2020 · 166 citations
- Adverse Drug Reaction Reporting in Africa and a Comparison of Individual Case Safety Report Characteristics Between Africa and the Rest of the World: Analyses of Spontaneous Reports in VigiBase® · Drug Safety · 2016 · 140 citations
- Factors Associated with Underreporting of Adverse Drug Reactions by Health Care Professionals: A Systematic Review Update · Drug Safety · 2023 · 127 citations
- Polypharmacy and falls in older people: Balancing evidence-based medicine against falls risk · Postgraduate Medicine · 2014 · 126 citations
- Strategies to reduce the risk of iatrogenic illness in complex older adults · Age and Ageing · 2013 · 113 citations
Most recent work
- Redefining Diagnostic and Management Approaches to Vancomycin Adverse Drug Reactions · The Journal of Allergy and Clinical Immunology In Practice · 2026
- Safety evaluation of Tofersen in amyotrophic lateral sclerosis based on the FAERS database · Frontiers in Neurology · 2026
- A real-world pharmacovigilance study of dacomitinib based on FDA adverse event reporting system (FAERS) database · Naunyn-Schmiedeberg s Archives of Pharmacology · 2026
- Drug-Induced Noninfectious Myocarditis/Pericarditis: A Real-World Pharmacovigilance Study Using the FAERS Database · Cardiovascular Toxicology · 2026
- Drug-associated oropharyngeal infection: a real-world pharmacovigilance study using the FDA adverse event reporting system database · BMC Oral Health · 2026
- Pharmacovigilance Analysis of Drug-Induced Stomatitis: Insights From Twenty-One Years of Real-World Data · International Dental Journal · 2026
- Verbal Expressions of Probability in Pharmacovigilance: Most Likely Too Ambiguous · Clinical Therapeutics · 2026
- Pharmacovigilance of carmustine: distinct neurotoxic and systemic safety signals identified in FAERS · BMC Cancer · 2026
- Global pharmacovigilance analysis of antimicrobials used in periodontal therapy: safety profiles of minocycline, doxycycline, and chlorhexidine · Head & Face Medicine · 2026
- CHRONOPHARMACOVIGILANCE: TIME-DEPENDENT PATTERNS OF ADVERSE DRUG REACTIONS AND THEIR REGULATORY IMPLICATIONS · Universal Journal of Pharmaceutical Research · 2026
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