Drug Safety最新文献

{"title":"Reassessing the Neoplasm Signal with Fezolinetant: Regulatory Inference, Mechanistic Plausibility, and the Case for Proactive Pharmacovigilance.","authors":"Glen Clack, Jennifer Renwick","doi":"10.1007/s40264-026-01737-8","DOIUrl":"https://doi.org/10.1007/s40264-026-01737-8","url":null,"abstract":"<p><p>Fezolinetant, the first neurokinin-3 receptor (NK3R) antagonist licensed for moderate-to-severe vasomotor symptoms associated with menopause, carries an unresolved neoplasm signal. An imbalance in neoplasm events across the SKYLIGHT phase III programme, raised in 2023, has been set aside by regulators as a chance finding lacking a plausible mechanism. We reassess that inference on three grounds. First, exposure-adjusted incidence of non-benign neoplasms rises across placebo, 30 mg and 45 mg, at 0.2, 0.7 and 1.2 per 100 subject-years, giving a relative risk at the licensed dose of 6.6 (95% confidence interval 0.9-51.3); a published recalculation gives 7.83 by counting 13 organ-class entries rather than 11 affected participants. The imbalance is dose related but not statistically significant. Second, of the 15 references mobilised in the European regulatory literature review to support that position, 11 concern the neurokinin-1 receptor or substance P rather than NK3R, two report NK3R expression in oral squamous cell carcinoma without administering an antagonist, one contains no neoplasm data and one alone administers an NK3R antagonist, finding that it reduced tumour burden. The pharmacology of the two receptors does not permit the extrapolation. Third, four mechanisms merit evaluation: loss of KISS1-mediated metastasis suppression and dormancy control, compensatory neurokinin-1 receptor activation by unbound neurokinin B, loss of anti-angiogenic restraint and acceleration of lesions already present. None requires de novo carcinogenesis, so the short-latency argument is not decisive. We recommend structured post-authorisation surveillance, a periodic independent safety review and re-examination of the mechanistic rationale.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Pharmacovigilance Outsourcing Practices in Arab Countries.","authors":"Ibrahim Abdeldayem, Thamir M Alshammari, Karine Palin","doi":"10.1007/s40264-026-01734-x","DOIUrl":"https://doi.org/10.1007/s40264-026-01734-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Outsourcing in pharmacovigilance has grown in the last decade. However, standards and references are lacking in this area, both for initiating and maintaining a long-term outsource relationship. There are differences in the progression of pharmacovigilance systems by regulatory agencies in these countries because only some can meet the requirements for conducting pharmacovigilance activities. This research aimed to provide an overview of the current pharmacovigilance outsourcing regulations in Arab countries, as well as recommending a draft guideline for good PV outsourcing practices that can be used as a starting point for the preparation of a pharmacovigilance outsourcing process standard.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The study was an observational study conducted during the period from 1 April 2020 to 31 July 2020, and was rechecked in July 2026 to search for the latest pharmacovigilance legislation on 22 countries that are considered members of Arab League. Regulatory authorities' websites were used as sources of information regarding the pharmacovigilance guidelines. Several documents were reviewed, including the Arab guideline on Good Pharmacovigilance Practices (GVP) version 2, guidelines for countries that have their discrete guidelines (e.g., Egypt, Saudi Arabia, United Arab Emirates (UAE), Algeria, Tunisia, Iraq, Lebanon, Oman, Sudan and Morocco). Additionally, a list of questions was designed for Arab health authorities regarding their current guidelines about pharmacovigilance outsourcing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the 22 Arab countries, 13 countries have pharmacovigilance guidelines; 8 of these 13 countries have pharmacovigilance guidelines with outsourcing sections. The Arab League guideline, Guidelines of Good Pharmacovigilance Practices in Egypt, and Saudi Food and Drug Authority Guideline on Good Pharmacovigilance Practices contain seven modules with outsourcing sections mentioned, while other Arab guidelines for Iraq and Tunisia contain only one module with outsourcing section mentioned.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study identified substantial variability in the extent and level of detail of pharmacovigilance outsourcing requirements across the national pharmacovigilance regulations of Arab countries, supporting the need for a more harmonized regional approach. Based on the identified gaps and existing principles of good pharmacovigilance outsourcing practice, the authors propose a structured framework for Good Pharmacovigilance Outsourcing Practice that may serve as a foundation for future regulatory harmonization and support marketing authorization holders, pharmacovigilance service providers, and regulatory authorities in establishing compliant and effective outsourcing arrangements. Further stakeholder consultation and validation are warranted to assess the applicability and feasibility of the proposed framework across different national pharmacovigilance systems in th","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disproportionality Analysis of FAERS Data Divergence and a Systematic Review of Comparative Safety Studies: Lessons Learned from the Example of Ranitidine and Cancer Risk.","authors":"Mahesh Rathod, Maheshwari Kadari, Haripriya R Mohan, Ruby Kasana, Mounika Katravath, Masao Iwagami, Krishna Undela","doi":"10.1007/s40264-026-01730-1","DOIUrl":"https://doi.org/10.1007/s40264-026-01730-1","url":null,"abstract":"<p><strong>Background: </strong>Ranitidine, a histamine-2 receptor antagonist, was withdrawn globally in 2020 following the detection of N-nitrosodimethylamine (NMDA), a probable human carcinogen.</p><p><strong>Objective: </strong>We aimed to assess advanced pharmacovigilance bias-mitigation approaches by evaluating ranitidine-associated cancer signals in the FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases alongside a systematic review of comparative safety studies.</p><p><strong>Methods: </strong>A retrospective disproportionality analysis was conducted using the FAERS and the JADER databases. Signal detection was performed using four complementary algorithms (proportional reporting ratio (PRR), reporting odds ratio, information component, and empirical Bayes geometric mean), with an active comparator (famotidine) and time-restricted (pre- and post-recall) analyses, and a systematic review of comparative safety studies was also conducted.</p><p><strong>Results: </strong>A pronounced surge in cancer reporting was observed for ranitidine, with 140,985 reports recorded in FAERS during 2020-21, accounting for more than two thirds of all reported cancer cases. Most reports were consumer submitted and geographically clustered in regions affected by regulatory actions and litigation. Unrestricted analyses of the full FAERS database identified high-magnitude signals for multiple cancers, particularly gastrointestinal and genitourinary cancers. However, these signals were markedly attenuated or absent in active-comparator and time-restricted analyses, with convergence observed in the reporting profiles of ranitidine and famotidine. In the JADER analysis, a significant ranitidine-cancer signal among suspected drug reports (PRR = 3.54) disappeared completely when all involvement types were analyzed (PRR = 0.92), indicating that the observed association likely reflects protopathic bias, rather than a true carcinogenic effect. The systematic review revealed heterogeneous findings, with most large cohort studies demonstrating no increased risk of overall or site-specific cancers.</p><p><strong>Conclusions: </strong>The observed cancer signals for ranitidine in spontaneous reporting systems were predominantly attributable to the NMDA related regulatory alerts rather than intrinsic carcinogenicity. Active-comparator and time-restricted analyses, together with systematic reviews of comparative safety studies, are essential to avoid misleading inferences in pharmacovigilance assessments.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switching Patterns of Oral Retinoids to Alternative Medications: An Interrupted Time-Series Analysis of Four European Countries.","authors":"Judit Riera-Arnau, Shahab Abtahi, Mònica Sabaté Gallego, Elena Ballarín, Magdalena Gamba, Romin Pajouheshnia, Vjola Hoxhaj, Ema Alsina, Mar Martin-Perez, Patricia Garcia-Poza, Ana Llorente-Garcia, Diana Gonzalez-Bermejo, Gabriel Sanfélix-Gimeno, Clara Rodríguez-Bernal, Salvador Peiró, Aníbal García-Sempere, Francisco Sánchez-Sáez, Valentina Ientile, Ylenia Ingrasciotta, Claudio Guarneri, Matilde Tanaglia, Michele Tari, Eline Houben, Rosa Gini, Giuseppe Roberto, Claudia Bartolini, Olga Paoletti, Giorgio Limoncella, Anna Girardi, Giulia Hyeraci, Sarah Brøgger Kristiansen, Olaf Klungel, Miriam Sturkenboom, Carlos E Durán","doi":"10.1007/s40264-026-01738-7","DOIUrl":"https://doi.org/10.1007/s40264-026-01738-7","url":null,"abstract":"<p><strong>Background and objective: </strong>The European Pregnancy Prevention Program for oral retinoids was updated in 2018, yet its impact on switching to retinoid alternative medications remains unclear. Thus, we aimed to measure its impact on the switching patterns from oral retinoids to retinoid alternative medications in women of childbearing potential in four European countries.</p><p><strong>Methods: </strong>A cross-sectional study was conducted in six databases across four European countries: the Netherlands (NL-PHARMO), Spain (ES-VID and ES-BIFAP), Italy (IT-ARS and IT-Caserta) and Denmark (DK-DNR), covering women of childbearing potential prescribed/dispensed oral retinoid between 2010 and 2020. The utilisation of retinoid alternative medications and switching from oral retinoids to retinoid alternative medications after discontinuation were measured. Changes in the rates of switching before and after implementation of the Pregnancy Prevention Program were analysed using an interrupted time series analysis.</p><p><strong>Results: </strong>From 88,992 women of childbearing potential previously exposed to retinoids, 32.0% (28,446) switched to a retinoid alternative medication over the study period. Overall, ten out of 80 median discontinuers per month switched. Median switching monthly rates ranged from 1.8 to 6.5% and from 1.2 to 2.3% pre-implementation and post-implementation, respectively. For overall switching rates, the interrupted time series analysis revealed a small but statistically significant decrease in slope post-intervention in IT-Caserta (- 0.035%; p < 0.01), ES-VID (- 0.04%; p < 0.01) and ES-BIFAP (- 0.03%; p = 0.02). These changes disappeared when excluding the coronavirus disease 2019 lockdown period from the analysis.</p><p><strong>Conclusions: </strong>The 2018 risk minimisation measures showed a limited impact on switching patterns, with possible differences between northern and southern countries. Further research is needed to investigate the reasons and choices behind switching, and the impact of the Pregnancy Prevention Program on the utilisation patterns of individual retinoid alternative medications, particularly those with teratogenic potential.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchical Algorithms for Constructing Mother-Father-Infant Linkages Under Modern Privacy Constraints.","authors":"Brian Meng-Hsun Li, Michael Chun-Yuan Cheng, Edward Chia-Cheng Lai","doi":"10.1007/s40264-026-01735-w","DOIUrl":"https://doi.org/10.1007/s40264-026-01735-w","url":null,"abstract":"<p><strong>Background: </strong>Post-marketing safety surveillance of medications used during pregnancy depends on accurate reconstruction of mother-father-infant triads in administrative healthcare data. However, global privacy regulations increasingly restrict the use of direct familial identifiers, and few parent-infant linkage algorithms have been validated against a reference standard.</p><p><strong>Objective: </strong>We aimed to develop and validate a hierarchical deterministic algorithm that constructs mother-infant and father-infant linkages from variables widely available in administrative healthcare data internationally.</p><p><strong>Methods: </strong>Using Taiwan's National Health Insurance Research Database and Birth Certificate Application database (2012-19), we constructed mother-infant and father-infant linkages through a five-step hierarchical mother-infant procedure and a single-step father-infant match, incorporating dependent-guarantor relationships, paternal demographic proxies, and sibling history. We validated the algorithm against the historical Maternal and Child Health Database, which provided a deterministic reference standard of 1,570,007 mother-infant and 1,510,578 father-infant pairs among 1,676,503 registered infants.</p><p><strong>Results: </strong>The algorithm identified 1,554,179 mother-infant pairs (positive predictive value 97.01%, 95% confidence interval [CI] 96.99-97.04; sensitivity 96.03%, 95% CI 96.00-96.06) and 1,036,980 father-infant pairs (positive predictive value 93.64%, 95% CI 93.59-93.69; sensitivity 64.28%, 95% CI 64.21-64.36). Mother-infant performance remained stable across the 8-year period, whereas paternal sensitivity showed a secular drift that we characterized to support recalibration in future birth cohorts.</p><p><strong>Conclusions: </strong>This hierarchical framework offers a reproducible, privacy regulation-compatible template for constructing parent-infant linkages to support pharmacovigilance research on parental medication exposures. Operating characteristics should be re-validated when the framework is applied in each new setting.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Monitoring of COVID-19 Vaccines in the Vaccine Adverse Event Reporting System (VAERS): United States, August 22, 2024-July 4, 2025.","authors":"Brittney Romanson, Pedro L Moro, Penelope Strid, Anne Hause, Erin Stroud, Paige L Marquez, Bicheng Zhang, Carol Ennulat, Hannah Brown, John R Su","doi":"10.1007/s40264-026-01709-y","DOIUrl":"https://doi.org/10.1007/s40264-026-01709-y","url":null,"abstract":"<p><strong>Background: </strong>The 2024-2025 formulation for all Coronavirus Disease 2019 (COVID-19) vaccines licensed or authorized in the United States (US) was updated to a monovalent vaccine based on the Omicron JN.1 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Post-authorization and post-approval safety monitoring is important to ensure ongoing vaccine safety.</p><p><strong>Objectives: </strong>The aim of this study was to evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS) among persons who received the 2024-2025 formulation of the COVID-19 vaccines in the US.</p><p><strong>Methods: </strong>We searched VAERS for US reports of individuals who received a COVID-19 vaccination and submitted a report during August 22, 2024, through July 4, 2025. Centers for Disease Control and Prevention (CDC) clinicians reviewed reports and available medical records for selected adverse events of special interest (AESIs) and serious reports. For reports of death, the reported cause of death was based on the International Classification of Disease, Tenth Revision (ICD-10) diagnostic categories reported on U.S. death certificates. For reports of anaphylaxis and Guillain-Barre syndrome (GBS), the Brighton Collaboration case definitions were used. For myocarditis, CDC's case definition was used. Reporting rates for the AESIs, excluding death, were estimated using vaccination coverage data for the 2024-2025 respiratory season.</p><p><strong>Results: </strong>VAERS received 9856 reports after 2024-2025 COVID-19 vaccination; 877 were serious (8.9%). The most common reported adverse events (AEs) included fever (854, 8.7%), pain (810, 8.2%), fatigue (785, 8.0%), headache (729, 7.4%), and dizziness (689, 7.0%). Of 273 deaths, cause of death was available for 97 reports, and the most common causes were diseases of the circulatory system (37, 38.1%), followed by diseases of the respiratory system (15, 15.5%). During the review period, no reports met the case definition of anaphylaxis, while eight reports met the Brighton case definition for GBS, and six reports met the case definition for myocarditis or myopericarditis. Death was not reported among the six myopericarditis cases. Reporting rates for GBS and myopericarditis were below background rates for these conditions.</p><p><strong>Conclusion: </strong>This review of AEs reported after the 2024-2025 formulation of the COVID-19 vaccines is consistent with previous observations after COVID-19 vaccination. Most reports were non-serious, and the most common AEs were consistent with known reactogenicity profiles. Ongoing safety monitoring of COVID-19 vaccines continues. Any potential risks of vaccine-related AEs should be considered in the context of the benefits of COVID-19 vaccines in preventing COVID-19 and its potentially serious complications.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consumer Views on the Role of the Natural Health Products (NHPs) Industry in Pharmacovigilance for NHPs: A Qualitative Study in New Zealand.","authors":"Xin Yi Lim, Shane Scahill, Sanyogita Ram, Joanne Barnes","doi":"10.1007/s40264-026-01732-z","DOIUrl":"https://doi.org/10.1007/s40264-026-01732-z","url":null,"abstract":"<p><strong>Introduction: </strong>Pharmacovigilance (safety monitoring) for natural health products (NHPs) is essential for consumer health protection. However, pharmacovigilance for NHPs is under-researched, especially regarding consumer involvement and the contributions of the NHPs industry.</p><p><strong>Objectives: </strong>This qualitative study aimed to explore consumers' views, experiences, and awareness of the NHPs industry's contributions to pharmacovigilance for NHPs in New Zealand.</p><p><strong>Methods: </strong>One-on-one online interviews were conducted with NHP consumers (n = 19) using a semi-structured interview schedule with the following domains: (1) meaning of terms (NHPs and pharmacovigilance); (2) pharmacovigilance for NHPs (including experiences with reporting adverse drug reactions (ADRs) to the NHPs industry); (3) views on NHP regulations and pharmacovigilance regulatory requirements for the NHPs industry; (4) a proposed active surveillance study for NHPs. Interviews were recorded, transcribed verbatim, and analysed inductively.</p><p><strong>Results: </strong>Five main themes were identified: (1) right to choose; (2) trust enables engagement; (3) considering information; (4) rationalising consumer protection; (5) perceiving and navigating risk. Participants exercised autonomy to self-select NHPs. Participants had limited experience with ADRs (associated with NHP use) and with reporting ADRs to the NHPs industry. Despite acknowledging that ethical standards varied across companies, participants expressed distrust of the industry's handling of ADRs, due to perceived conflicts of interest and a lack of transparency. Participants' self-responsibility, underscored by autonomy and lack of trust in the industry, appeared to be significant barriers to the industry's involvement in pharmacovigilance for NHPs. Despite low awareness of NHP regulations, participants held expectations for regulatory requirements that balance product accessibility and safety controls.</p><p><strong>Conclusion: </strong>Participants (consumers of NHPs) had minimal engagement with the NHPs industry regarding pharmacovigilance. Raising awareness of the potential harms associated with NHP use, improving knowledge of channels for reporting ADRs, and fostering trust in the industry's handling of ADR reports could empower consumers and enable the industry to assume a more active and significant role in pharmacovigilance for NHPs. Quantitative studies involving larger samples of NHP consumers are necessary to corroborate these findings.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.","authors":"Wei Kang, Bowie P Y Lam, Rinko Tsz Lam Lau, Silvia T H Li, Kangrui Wu, Yue Wei, Yu Yang, Kyung Jin Lee, Caige Huang, Vincent K C Yan, Hei Hang Edmund Yiu, Shing Fung Lee, Aya El Helali, Victor H F Lee, Stephen L Chan, Rina Y M Hui, Ka On Lam, Esther W Chan","doi":"10.1007/s40264-026-01684-4","DOIUrl":"10.1007/s40264-026-01684-4","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations.</p><p><strong>Objective: </strong>This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period.</p><p><strong>Methods: </strong>PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis.</p><p><strong>Results: </strong>Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72).</p><p><strong>Conclusions: </strong>In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1161-1180"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISoP MENA Chapter: Strategic Development and Future Directions Following a Decade of Strengthening Pharmacovigilance in the Middle East and North Africa.","authors":"Hadir Rostom, Mohamed A Elhawary, Mayada Alkhakany, Manal M Younus, Thamir Alshammari, Felipe Villalobos, Omar Aimer","doi":"10.1007/s40264-026-01723-0","DOIUrl":"10.1007/s40264-026-01723-0","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1113-1118"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Large Language Model for Extracting Post-marketing Adverse Drug Events from Clinical Notes in the Electronic Health Record.","authors":"Dana Ludwig, Michelle Wang, James Buchanan, Trang Trinh","doi":"10.1007/s40264-026-01682-6","DOIUrl":"10.1007/s40264-026-01682-6","url":null,"abstract":"<p><strong>Background: </strong>Clinical notes contain a vast amount of potentially useful information about adverse drug event (ADE) signals that never reach pharmacovigilance databases. Traditional rule-based or sentence-level models often miss subtle causal cues and generate excess false positives.</p><p><strong>Objective: </strong>To build a large language model (LLM) pipeline that reads entire electronic health record (EHR) notes, identifies drug-event pairs with a \"reasonable possibility\" of causation, and infers other important properties of each ADR, such whether the event is \"serious\" or \"unlabeled\".</p><p><strong>Methods: </strong>We adopted a two-pass workflow using model \"OpenAI o1\": Pass 1 screens each note for ADEs; Pass 2 adds 20 structured fields. A diverse sample of 372 deidentified notes from physicians and pharmacists at the University of California, San Francisco (UCSF), from 31 specialty/setting cells, yielded 191 ADEs. One medical expert reviewed each ADE for validity, seriousness, and label status. Another expert created a gold standard manually curated ADE set on 100 of the 372 ADEs to give us a percent \"recall\" estimate. A third expert met with the first expert to arrive at a consensus on the validity of LLM ADEs validated by the first expert but not found in the gold standard ADEs, giving us a estimate of \"accuracy\".</p><p><strong>Results: </strong>Of 191 ADEs, 180 were true positives (94.2% precision) with 84.1% recall (F1 = 88.9%). Seriousness was correct in 100% and label status in 93.9% of cases. Medical Dictionary for Regulatory Activities (MedDRA) lowest level term (LLT) coding was correct in 92.5% of valid ADEs; errors were mostly non-existent LLTs. Of all valid ADEs, 12.2% met FDA \"serious\" criteria, 15.0% were unlabeled, and 8.9% were \"failure of efficacy.\" On the first pass, 84.9% of notes contained no ADEs, keeping inference costs to USD $0.18 per note and $0.35 per validated ADE. The model inferred some ADEs not mentioned by physicians, e.g., tacrolimus-associated hypomagnesemia.</p><p><strong>Conclusions: </strong>While the LLM evaluated in this study is not perfect, it can transform free-text EHR notes into ADEs with 94% accuracy, and such data, when statistically analyzed in aggregate, can lead to new safety signals of potential drug side effects. Integrated with platforms like Sentinel in the USA, or Darwin EU, in the European Union, this approach could rapidly surface rare, serious, and unlabeled ADEs for further regulatory analysis.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1181-1198"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}