Drug Safety最新文献

{"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}

{"title":"The Value of Time-to-Onset for Signal Validation: Experience from the Reporting of COVID-19 Vaccines and Glomerular Diseases in VigiBase.","authors":"Annette Rudolph, Monica Tarapues, Oskar Gauffin, Qun-Ying Yue","doi":"10.1007/s40264-026-01711-4","DOIUrl":"https://doi.org/10.1007/s40264-026-01711-4","url":null,"abstract":"<p><strong>Background: </strong>Adverse event reports of glomerular diseases (GDs) following coronavirus disease 2019 (COVID-19) vaccination collected nationally have been shared to VigiBase, the global database of adverse event reports for medicines and vaccines. From literature reports, different GDs following COVID-19 vaccination have different time-to-onsets (TTOs), highlighting the potential value of TTO in suggesting underlying disease mechanisms and supporting its relevance in signal validation prior to in-depth signal assessment.</p><p><strong>Objective: </strong>The aim of this study was to characterise the TTO in reports of GDs in association with COVID-19 vaccines inVigiBase. The analysis focuses on exploring the value of TTO for signal validation, an early step preceding signal assessment.</p><p><strong>Methods: </strong>Reports for four different GDs in association with COVID-19 vaccines were extracted from VigiBase on 3 April, 2023. The reports were de-duplicated and TTO information was manually verified. Demographics and clinical characteristics were summarised per GD. The median TTO was compared between GDs and by disease status (relapse and new onset cases) within each GD.</p><p><strong>Results: </strong>In the extracted data, 245 unique cases shared to VigiBase and containing information about both TTO and disease status for the four selected GDs in association with COVID-19 vaccines were identified. Reports for IgA nephropathy represented the majority (49%). Most of the GD cases concerned messenger RNA COVID-19 vaccines (84%) and most occurred following the second dose (54%). Differences in median TTO between the four GDs as well as between disease status within the GDs were observed. However, except between IgA nephropathy and the other three GDs, these differences were not statistically significant.</p><p><strong>Conclusions: </strong>This study explores TTO differences for four different GDs following COVID-19 vaccination, taking new onset or relapse cases into account. The study demonstrates how review and characterisation of TTO data can complement traditional disproportionality analysis in the early stage of signal validation. The presented hypothesis will require further investigation.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105692","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":"Assessing the Risk of Adverse Maternal and Infant Outcomes Following Prenatal Modafinil Exposure: A French Nationwide Cohort Study.","authors":"Sigal Kaplan, Julie de Nascimento, Andrea Contini","doi":"10.1007/s40264-026-01686-2","DOIUrl":"10.1007/s40264-026-01686-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Concerns about modafinil and armodafinil use in pregnancy emerged from animal reproductive toxicity and limited human data, including a US registry suggesting increased risk of major congenital malformations (MCMs). Subsequent studies have reported conflicting findings. This study aimed to evaluate the risk of MCMs and other adverse pregnancy outcomes following prenatal modafinil exposure in the French population.</p><p><strong>Methods: </strong>This retrospective cohort study identified pregnancies during 2012-2019 using the French national health database (SNDS). Pregnancies exposed and unexposed to modafinil were identified and propensity score matched (1:4 ratio). Outcomes assessed included MCMs, spontaneous abortion, stillbirth, elective termination, preterm birth, low birth weight, and growth restriction. Prevalence and prevalence ratios (PRs) were calculated and adjusted risk ratios (RR) were estimated using Poisson regression models.</p><p><strong>Results: </strong>A total of 786 modafinil-exposed pregnancies were matched to 3144 unexposed pregnancies. The prevalence of MCMs among first-trimester modafinil-exposed pregnancies was 4.2%, compared with 3.3% in unexposed pregnancies (PR 1.26; 95% CI 0.77-2.04). After adjustment for potential confounding factors, no statistically significant increase in MCM risk was observed (RR 1.32, 95% CI 0.81-2.15). Most other pregnancy and birth outcomes showed no significant differences. However, elective terminations were 32% more frequent in the exposed group (PR 1.32; 95% CI 1.14-1.51).</p><p><strong>Discussion: </strong>This large, population-based study found no increased risk of MCMs or most adverse pregnancy outcomes following modafinil exposure. The elevated rate of elective terminations may reflect clinical decisions influenced by underlying maternal conditions such as narcolepsy. While these findings do not indicate an increased risk of MCM, caution remains warranted regarding modafinil use during pregnancy.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1211-1222"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216321","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":"Developing a Hierarchical Algorithm to Identify Pregnancies and Determine Gestational Age from Nationwide Linked Health Data in Taiwan.","authors":"Miyuki Hsing-Chun Hsieh, Zoe Chi-Jui Chang, Chih-Wan Lin, Brian Meng-Hsun Li, Edward Chia-Cheng Lai, Wan-Ting Huang","doi":"10.1007/s40264-026-01688-0","DOIUrl":"10.1007/s40264-026-01688-0","url":null,"abstract":"<p><strong>Background: </strong>Administrative health data are vital for investigating medication safety during pregnancy. In Taiwan, while the National Health Insurance Research Database (NHIRD) and Birth Certificate Application (BCA) capture pregnancy data, no standardized approach exists for integrating these sources to identify episodes and assign gestational age (GA). This study aimed to develop a hierarchical pregnancy-identification algorithm tailored to Taiwan's linked claims and birth registry data.</p><p><strong>Methods: </strong>We adapted an ICD-10-CM/PCS-based algorithm to the Taiwanese coding environment, incorporating clinician input, local billing practices, and birth registry information. The algorithm refines pregnancy outcome classification, estimates pregnancy start dates, and assigns GA. As a proof of concept, we applied the final algorithm to 2016-2022 data to summarize outcome distributions.</p><p><strong>Results: </strong>We developed a seven-step hierarchical algorithm that uses claims codes to classify pregnancy outcomes, groups records into episodes using spacing rules, assigns pregnancy start dates from ordered prenatal services, validates and refines GA via linkage to the BCA database, determines the number of pregnancies and fetuses, and checks the plausibility of GA and inter-pregnancy intervals. A total of 1,696,229 pregnancies contributed by 1,169,779 women were identified; outcome distributions (69.3% live birth, 16.3% spontaneous abortion, 5.7% elective abortion, 6.0% ectopic pregnancy, 1.4% delivery with unknown outcome, 1.1% stillbirth, 0.2% trophoblastic and other abnormal products of conception) were consistent with national statistics and prior literature.</p><p><strong>Conclusions: </strong>This hierarchical algorithm provides a transparent, reproducible framework for identifying pregnancies and estimating GA in Taiwan. It establishes a critical foundation for future real-world studies of medication safety during pregnancy.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1223-1236"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293806","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":"Drug Brand Switching: A Regulatory Perspective.","authors":"Ping Siu Kee, Paul K L Chin, Michael Tatley, Rhiannon Braund, Martin A Kennedy, Simran D S Maggo","doi":"10.1007/s40264-026-01712-3","DOIUrl":"https://doi.org/10.1007/s40264-026-01712-3","url":null,"abstract":"<p><p>The replacement of expensive medications marketed by companies that bore the cost of development and testing, by low-cost \"generics\" once patent protection ends, is a common step in the life cycle of most drugs. Although generics are required to meet strict bioequivalence standards, the introduction of first-time and subsequent generics may lead to unease and increased reports of adverse effects or therapeutic failure. An established causal relationship between these effects and the switch from innovator to generic products can be challenging to assess. With the ongoing debate, this paper primarily explores how the regulatory framework governing generic drug approval may have contributed to this medical conundrum. In addition, we also offer a perspective on the potential role of pharmacogenetics within this setting.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105659","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 Management of Targeted Therapies for Relapsed/Refractory Chronic Lymphocytic Leukemia.","authors":"Sikander Ailawadhi, Elcin Omercikoglu, Aneel Paulus, Ricardo D Parrondo, Asher A Chanan-Khan","doi":"10.1007/s40264-026-01678-2","DOIUrl":"10.1007/s40264-026-01678-2","url":null,"abstract":"<p><p>Targeted therapies have transformed the treatment landscape for patients with chronic lymphocytic leukemia (CLL). These therapies include the selective B-cell lymphoma-2 (BCL-2) inhibitor venetoclax and Bruton's tyrosine kinase (BTK) inhibitors (e.g., ibrutinib, acalabrutinib, zanubrutinib). Especially in a setting of long-term care, safety and tolerability are important considerations. Although generally well tolerated, targeted therapies for relapsed and refractory CLL are associated with potentially treatment-limiting untoward effects, often within weeks to months of initiating therapy. These include myelosuppression (e.g., neutropenia); tumor lysis syndrome, infection, and gastrointestinal effects with venetoclax; as well as cardiovascular diseases (e.g., hypertension, atrial fibrillation/flutter) and infection (e.g., pneumonia) with BTK inhibitors. Instrumental to management of these adverse effects are effective risk assessment, stratification, and modification; prophylaxis; and regimen modifications, with appropriate measures to minimize pharmacokinetic interactions.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1135-1159"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454992","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":"Analytic Misjudgment of Drug Safety Evidence and Causality: From the Prosecutor's Fallacy and Simpson's Paradox to Artificial Intelligence.","authors":"Tarek A Hammad, Justine Rochon","doi":"10.1007/s40264-026-01683-5","DOIUrl":"10.1007/s40264-026-01683-5","url":null,"abstract":"<p><p>Drug safety assessment, particularly in the post-marketing setting, is especially vulnerable to analytic misjudgment because it relies on heterogeneous evidence streams, incomplete data, infrequent events, and decisions made under substantial uncertainty. Recurring sources of error include misinterpretation of conditional probabilities, conflation of association with causation, inappropriate denominator and comparator selection, inadequate consideration of background incidence and confounding, aggregation artifacts such as Simpson's paradox, and overinterpretation of exploratory findings arising from multiplicity or repeated testing. Misjudgment may be further amplified by spontaneous reporting data that lack explicit exposure denominators and are susceptible to reporting bias, by fragile or incomplete meta-analyses, and by premature regulatory or public responses to weak or incompletely contextualized signals. Using selected real-world case studies and conceptual examples, this narrative review illustrates how such errors arise and propagate across clinical, regulatory, and public domains, and how they can materially influence causality assessment and decision making. The paper also discusses how artificial intelligence (AI), if implemented without transparency, bias assessment, and clinical oversight, may amplify rather than reduce these vulnerabilities. Greater analytic discipline, clearer communication of uncertainty, triangulation across evidence streams, and careful governance of emerging AI-enabled tools are needed to support more reliable drug safety evaluation.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1119-1133"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223826","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":"Enhancing Disease Surveillance and Pharmacovigilance Practices for RTS,S/AS01_E Malaria Vaccine Rollout in Ghana, Kenya, and Malawi: Strategies, Impact, Challenges, and Lessons Learned.","authors":"Valérie Haine, Tene-Alima Essoh, Caroline Perrin Franck, Miloje Savic","doi":"10.1007/s40264-026-01685-3","DOIUrl":"10.1007/s40264-026-01685-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The rollout of new vaccines in low- and middle-income countries often faces significant challenges due to underdeveloped disease surveillance and pharmacovigilance practices for monitoring vaccine safety and effectiveness. In 2019, RTS,S/AS01&lt;sub&gt;E&lt;/sub&gt;, the first malaria vaccine to demonstrate efficacy, was piloted in selected regions of Ghana, Kenya, and Malawi to evaluate RTS,S/AS01&lt;sub&gt;E&lt;/sub&gt; real-world safety, effectiveness, impact, and operational feasibility. To strengthen safety monitoring and to gather additional data during rollout, several phase IV studies were conducted that included a capacity-building initiative to enhance disease surveillance and pharmacovigilance practices among healthcare professionals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Here, we describe the capacity-building experience, including targeted training strategies and accompanying paper-based and digital tools developed to improve detection, diagnosis, and reporting of adverse events of special interest (AESIs) and adverse events following immunization (AEFIs). We summarize the impact of the initiative, challenges, and actions taken, and share lessons learned to guide future capacity-building initiatives in low- and middle-income countries.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The initiative included tailored, frequent, 2-day in-person training sessions for both medical and non-medical professionals in hospital and community settings, complemented by online courses, practical job aids, a tele-expertise platform, and a mobile alert system to improve adverse event reporting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The initiative reached approximately 5000 community healthcare professionals and 1000 study staff. Knowledge assessments after the trainings indicated marked improvements, with scores increasing from 41% to 72% among medical professionals and from 38% to 68% among non-medical professionals after initial training; similar gains were observed after refresher training (45% to 74% and 45% to 72%, respectively). Across the three countries involved in the pilot implementation, 90% of reported AESIs and AEFIs were documented through the phase IV studies. Trainings were generally well received; however, digital tools were underutilized due to the perceived operational burden and user preferences. The repeated use of similar training materials across sessions required the introduction of new clinical cases and knowledge quizzes to maintain participant engagement. In addition, resource limitations, including intermittent connectivity and logistical constraints, posed practical challenges.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This experience highlights the importance of tailored training, flexibility, collaboration, and prior alignment on integrating new tools into existing procedures. Overall, our approach may offer valuable insights for future pharmacovigilance capacity-building efforts in low- and middle-income countries to support safer vaccine ro","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1199-1210"},"PeriodicalIF":5.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435558","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":"Signal Detection of Adverse Events Associated with PCSK9 Inhibitors: A Nationwide Sequence Symmetry and Combined Worldwide Disproportionality Analysis.","authors":"Thibault Viguier, Julien Bezin, Alex Hlavaty, Charles Khouri, Antoine Pariente","doi":"10.1007/s40264-026-01731-0","DOIUrl":"https://doi.org/10.1007/s40264-026-01731-0","url":null,"abstract":"<p><strong>Background and aim: </strong>Despite the increasing use of proprotein convertase subtilisin/kexin type 9-inhibitors (PCSK9i), their safety assessment from large real-world databases remains limited. We aimed to perform a large-scale safety signals detection study regarding PCSK9i.</p><p><strong>Methods: </strong>A sequence symmetry analysis (SSA) was conducted using the French nationwide health system databases (SNDS); PCSK9i initiators (2018-2023 time-period) were matched to ezetimibe ones, to control for temporal trends and potential indication bias. Outcomes of interest included all designated medical events (DMEs) and all drug classes considered by Anatomical Therapeutic Chemical (ATC) classification levels III and IV. In SSAs, potential safety signals for PCSK9i were defined as the combination of both a crude sequence ratio (SRc) and an ezetimibe-adjusted one (SRa) with a 95% confidence interval (CI) lower limit exceeding 1. For the outcomes corresponding to DMEs, disproportionality analyses were performed in the World Health Organization (WHO) pharmacovigilance database VigiBase^® to complete the assessment.</p><p><strong>Results: </strong>In total, sequence symmetries could be studied for 36,163 PCSK9i initiators and 34,269 ezetimibe ones. Over the 700 outcomes analyzed, two potential signals were identified via SSA, that related to ATC-III drug initiations for inhaled glucocorticoids (SRc: 1.25 [1.16-1.38]; SRa: 1.19 [1.06-1.35]) and colony stimulating factors (SRc: 4.22 [2.81-6.71]; SRa: 2.25 [1.37-4.17]); they were duplicated when considering the corresponding ATC-IV classes. No related signal was detected in VigiBase^®.</p><p><strong>Conclusions: </strong>This study, combining analyses from large medico-administrative and spontaneous reports databases, identified only two potential signals relating to PCSK9i. Both appeared to be linked to residual indication bias or confounding factors.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024077","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}