Drug Safety最新文献

{"title":"Prenatal Exposure to Proton Pump Inhibitors and Risk of Serious Infections in Offspring During the First Year of Life: A Nationwide Cohort Study.","authors":"Mylène Tisseyre, Mathis Collier, Nathanaël Beeker, Florentia Kaguelidou, Jean-Marc Treluyer, Laurent Chouchana","doi":"10.1007/s40264-024-01496-4","DOIUrl":"10.1007/s40264-024-01496-4","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Proton pump inhibitor (PPI) use in children increases the risk of infections, prompting inquiry into the impact of prenatal PPIs exposure on serious infections in offspring. As a research gap in this area exists, this study aimed to address it by assessing the association between prenatal PPIs exposure and serious infections in infants during their first year of life.</p><p><strong>Methods: </strong>Using the French health insurance data warehouse (SNDS) (2013-2018), we conducted a retrospective cohort study on singleton, full-term liveborn non-immunocompromised infants, stratified by PPI use during the first three months of life (early-life use). Proton pump inhibitor dispensing in ambulatory care settings during pregnancy defined exposure. Outcomes concerned any serious infections in offspring aged between 3 and 12 months. Adjusted odds ratios (aORs) were estimated using logistic regression with multivariable models to control for potential confounders.</p><p><strong>Results: </strong>Of the 2,485,545 infants included, 497,060 (23.3%) were prenatally exposed to PPIs and 97,767 (4.6%) had PPI use during the first three months of life. Prenatal PPI exposure was associated with serious infections in offspring (aOR, 1.09 [95% CI, 1.07-1.10]) in infants without early-life PPIs use. No association was found for infants with early-life PPI use (aOR, 1.05 [95% CI, 1.00-1.11]). Gastrointestinal infections were the sole site with persistent significance.</p><p><strong>Conclusion: </strong>Prenatal PPI exposure is common and is not associated with a major risk of serious infections in infants during their first year. However, even after adjusting for several confounding factors, a weak association remains, especially in infants without early-life PPI use. While offering reassurance, adherence to clinical guidelines is still crucial.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"265-277"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767382","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":"Early Detection of Hearing Impairment Signals Post-mRNA COVID-19 Vaccination: A Disproportionality Analysis Study on French Pharmacovigilance Database.","authors":"Dalil Boulefaa, Haleh Bagheri, Francesco Salvo, Marie-Blanche Rabier, Hélène Geniaux, Marion Lepelley, Fanny Rocher, Julien Mahe, Aurélie Grandvillemuin, Hung Thai-Van","doi":"10.1007/s40264-024-01495-5","DOIUrl":"10.1007/s40264-024-01495-5","url":null,"abstract":"<p><strong>Introduction: </strong>Improving adverse events following immunisation (AEFI) detection is vital for vaccine safety surveillance, as an early safety signal can help minimize risks. In February 2022, the World Health Organization reported a preliminary signal on sudden sensorineural hearing loss (SSNHL) following coronavirus disease 2019 (COVID-19) vaccination, 54 million persons in France received at least one dose, covering 78.8% of the population within a year.</p><p><strong>Objective: </strong>The primary objective of this study was to identify a method of disproportionality analysis capable to detect a safety signal for hearing impairment (HI) as early as possible during the initial phases of the COVID-19 vaccination campaign. Secondly, we described all cases of SSNHL reported during vaccine booster campaigns in France.</p><p><strong>Methods: </strong>Data from January 2011 to February 2022 were extracted from the French pharmacovigilance database. Cases were all spontaneous reports of AEFI for elasomeran and tozinameran, while non-cases were AEFI reported for other vaccines. Disproportionality analysis for HI was performed monthly during 2021, to estimate a reporting odds ratio (ROR). Four different methods were used for ROR estimation. Furthermore, we reviewed cases of SSNHL following messenger RNA COVID-19 vaccinations reported during booster campaigns, from 2 February 2022 to 1 March 2023, based on a comprehensive medical evaluation.</p><p><strong>Results: </strong>Using a standard methodology, we identified a signal on 31 July 2021 (ROR 1.50, 95% confidence interval [CI] [1.06-2.18]). Multivariate analysis adjusted for sex, age, ototoxic drugs and excluding reference reports of common AEFI for vaccines allowed us to detect the HI signal as early as 31 March 2021 (ROR 2.67, 95% CI [1.36-5.57]). The SSNHL reporting rate was estimated to be 0.83/1,000,000 doses for tozinameran and 4.3/1,000,000 for elasomeran during the booster campaigns.</p><p><strong>Conclusion: </strong>Using a well-structured disproportionality analysis could have enhanced early detection of safety signals and contribute to risk minimizing measures. According to descriptive data, HI following mRNA COVID-19 vaccines remains rare.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"251-263"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784558","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":"Antiretroviral Use for HIV Prevention During Pregnancy: The Need to Strengthen Regulatory and Surveillance Systems in Africa.","authors":"Robin Schaefer, L Donaldson, A Chigome, M Escudeiro Dos Santos, S Lamprianou, N Ndembi, J I Nwokike, P Nyambayo, V Palmi, F Renaud, M Gonzalez Tome, V Miller","doi":"10.1007/s40264-024-01494-6","DOIUrl":"10.1007/s40264-024-01494-6","url":null,"abstract":"<p><p>HIV-prevention efforts focusing on women of child-bearing potential are needed to end the HIV epidemic in the African region. The use of antiretroviral drugs as pre-exposure prophylaxis (PrEP) is a critical HIV prevention tool. However, safety data on new antiretrovirals during pregnancy are often limited because pregnant people are excluded from drug development studies. Calls from communities, healthcare professionals, and regulators to improve the information supporting decision-making around the use of medical products during pregnancy have been increasing. Post-marketing safety surveillance is an essential tool for detecting adverse outcomes and evaluating real-world, longer-term effects of drugs. Detecting and evaluating uncommon pregnancy outcomes requires large sample sizes, highlighting the benefits of and need for safety surveillance. Surveillance systems vary widely across Africa, and the need for enhanced surveillance of PrEP use during pregnancy highlights the limitations of current regulatory and surveillance systems. Challenges include weak regulation and insufficient resources. Pooling of resources and regulatory harmonization could address resource challenges. The African Medicines Agency, as a specialized agency of the African Union, has the potential to improve African medical product regulation, including post-marketing safety surveillance. This can strengthen regulation and ensure that market authorization holders meet their responsibility to invest in post-marketing surveillance systems, such as pregnancy registries. At the same time, independent post-marketing studies are needed to ensure generation of essential safety data. The Forum for Collaborative Research has initiated a project to facilitate interactions between regulators in Africa, the USA, and Europe, as well as other stakeholders, and to work toward consensus on safety data generation from PrEP during pregnancy before and after marketing authorization.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"209-216"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051984","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":"Understanding the Work of the Pharmacovigilance Risk Assessment Committee (PRAC): A Quantitative Review of the Post-Authorisation Safety Evaluation of Antidiabetic Drugs from 2012 to 2022.","authors":"Haoxin Le, Per Sindahl, Morten Andersen, Christine E Hallgreen","doi":"10.1007/s40264-025-01536-7","DOIUrl":"https://doi.org/10.1007/s40264-025-01536-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The Pharmacovigilance Risk Assessment Committee (PRAC) plays a central role in the European Union's pharmacovigilance system, evaluating drug safety through several procedures and activities. Despite its central role, few studies have quantitatively investigated the PRAC's activities from a system's perspective.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to map PRAC's evaluation of safety signals and concerns using antidiabetic products as a case. It characterises the drugs and adverse events involved, analyses the PRAC-led regulatory procedures where the safety signals and concerns were evaluated, and provides a comprehensive review of PRAC meeting minutes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;From PRAC meeting minutes, we retrieved information on all antidiabetic drug-related adverse events discussed from 2012 to 2022. We identified drug-adverse event evaluations based on the discussion content. These were described by drug classes, System Organ Classes, PRAC procedures, and the evaluation outcomes corresponding to recommendations for regulatory actions. We also analysed the sequence of PRAC-led procedures and activities addressing drug-adverse event pairs across meeting minutes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 321 drug-adverse event pairs were identified, with 14 pairs associated with drug classes. Second-generation antidiabetic agents, including sodium-glucose transport protein-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase 4 inhibitors, were the most frequently discussed. Of these, 62 pairs underwent multiple evaluations, resulting in a total of 413 evaluations. In 48% of evaluations, no regulatory action was required. Most evaluations (97%) were concluded in a single procedure, and 66% were concluded in one meeting. Periodic safety update reports accounted for 54% of drug-adverse event evaluations and updates to product information were the most frequent outcome. Signal assessment and prioritisation procedures, while less common, resulted in more diverse recommendations for regulatory action. Referrals were infrequent (N = 5) and were often triggered by the signal assessment and prioritisation procedure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Periodic safety update reports are the primary source for PRAC evaluations of safety signals although they are not intended for notification of new urgent safety information. Compared with periodic safety update reports, the signal assessment and prioritisation procedure evaluates fewer signals but leads to a wider range of regulatory actions, from risk minimisation measures to referrals. This difference may be attributed to the fact that signals detected in periodic safety update reports are not intended for urgent safety issues, these should be assessed through the signal assessment and prioritisation procedure, as the latter involves real-time signal management, whereas the periodic safety update reports are conducted at pr","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536898","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":"Stakeholders' Perspectives Toward the Use of Patient Registry Data for Decision-Making on Medicines: A Cross-Sectional Survey.","authors":"Fabian Windfuhr, Sieta T de Vries, Maria Melinder, Tanja Dahlqvist, Diogo Almeida, Bruno Sepodes, Carla Torre, Björn Wettermark, Peter G M Mol","doi":"10.1007/s40264-025-01528-7","DOIUrl":"https://doi.org/10.1007/s40264-025-01528-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The use of patient registries in regulatory, health technology assessment (HTA), and payer decision-making has gained increasing attention in recent years. Stakeholders' perspectives toward the use of registry-based real-world evidence (RWE) are unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The purpose of this study was to assess stakeholders' perspectives toward the use of RWE from patient registries in decision-making on medicines and explore factors influencing their intention to use registry data in the future.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;European regulators, HTA/payers, and other stakeholders (industry, academia, healthcare professionals, patient representatives) were invited by email to participate in a web-based survey. The survey was open between November 2023 and January 2024 and contained 24 questions including demographics and questions about perspectives toward registry-based data for decision-making purposes. The latter consisted of 5-point Likert scale items based on the theory of planned behavior (TPB), i.e., attitudes, subjective norm, perceived behavioral control, and intention. Descriptive analyses and a logistic regression analysis (outcome: intention; determinants: demographics, attitudes, subjective norm, behavioral control) were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Included were 191 respondents (response rate: 16%), of whom 110 were regulators (58%), 24 HTA/payers (13%), and 54 other stakeholders (28%). Most respondents were between 41 and 50 years old (32%), 65% were women, and 53% had &gt; 10 years work experience. Respondents considered registry data in the medicinal product lifecycle most informative for characterization of disease epidemiology (mean 4.4; 95% confidence interval (CI) 4.2-4.5), and least informative for comparative effectiveness (mean 3.6; 95% CI 3.4-3.7). Reaching the relevant patient population was perceived as the biggest strength (mean 3.6; 95% CI 3.4-3.8), and data quality as the largest weakness of patient registries (mean 2.4; 95% CI 2.2-2.6). Compared with regulators, HTA/payers had a similar intention to use registry data (Odds ratio (OR) 1.56; 95% CI 0.47-5.16), while other stakeholders were more frequently very open (intention) to using registry data in the future (OR 8.48; 95% CI 3.00-23.98). Respondents from organizations in Northern Europe were less often very open to using registry data in the future than respondents from multinational organizations (OR 0.19; 95% CI 0.04-0.85). Finally, respondents with a high perceived behavioral control concerning the use of registry data were more often very open to using registry data in the future than respondents with a neutral or low perceived behavioral control (OR 3.45; 95% CI 1.37-8.64).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The participants in our survey were generally open to increasing the use of registry data in the future. Nevertheless, perceived weaknesses such as data quality and accessibility will need to","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482529","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":"Are Causal Statements Reported in Pharmacovigilance Disproportionality Analyses Using Individual Case Safety Reports Exaggerated in Related Citations? A Meta-epidemiological Study.","authors":"Claire Bernardeau, Bruno Revol, Francesco Salvo, Michele Fusaroli, Emanuel Raschi, Jean-Luc Cracowski, Matthieu Roustit, Charles Khouri","doi":"10.1007/s40264-025-01524-x","DOIUrl":"https://doi.org/10.1007/s40264-025-01524-x","url":null,"abstract":"<p><strong>Background: </strong>Previous meta-epidemiological surveys have found considerable misinterpretation of results of disproportionality analyses. We aim to explore the relationship between the strength of causal statements used in title and abstract conclusions of pharmacovigilance disproportionality analyses and the strength of causal language used in citing studies.</p><p><strong>Methods: </strong>On March 30, 2022, we selected the 30 disproportionality studies with the highest Altmetric Attention Scores. For each article, we extracted all citing studies using the Dimension database (n = 1434). In parallel, two authors assessed the strength of causal statements in the title and abstract conclusions of source articles and in the paragraph of citing studies. Based on previous studies, the strength of causal language was quantified based on a four-level scale (1-appropriate interpretation; 2-ambiguous interpretation; 3-conditionally causal; 4-unconditionally causal). Discrepancies were solved by discussion until consensus among the team. We assessed the association between the strength of causal statements in source articles and citing studies, separately for the title and abstract conclusions, through multinomial regression models.</p><p><strong>Results: </strong>Overall, 27% (n = 8) of source studies used unconditionally causal statements in their title, 30% (n = 9) in their abstract conclusion, and 17% (n = 5) in both. Only 20% (n = 6) used appropriate statements in their title and in their abstract's conclusions. Among the 622 citing studies analyzed, 285 (45.8%) used unconditionally causal statements when referring to the findings from disproportionality analysis, and only 164 (26.4%) used appropriate language. Multinomial models found that the strength of causal statements in citing studies was positively associated with the strength of causal language used in abstract conclusions of source articles (Likelihood Ratio Test (LogLRT) p < 0.00001) but not in the titles. In particular, among studies citing source articles with appropriate interpretation, 30.2% (95% confidence interval [CI] 22.8-37.6) contained unconditionally causal statements in their abstract conclusions, versus 56.4% (95% CI 48.7-64.2) for studies citing source articles with unconditionally causal statements.</p><p><strong>Conclusions: </strong>Nearly half of the studies citing pharmacovigilance disproportionality analyses results used causal claims, particularly when the causal language used in the source article was stronger. There is a need for higher caution when writing, interpreting, and citing disproportionality studies.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476359","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":"Effectiveness of Transformer-Based Large Language Models in Identifying Adverse Drug Reaction Relations from Unstructured Discharge Summaries in Singapore.","authors":"Yen Ling Koon, Yan Tung Lam, Hui Xing Tan, Desmond Hwee Chun Teo, Jing Wei Neo, Aaron Jun Yi Yap, Pei San Ang, Celine Ping Wei Loke, Mun Yee Tham, Siew Har Tan, Sally Leng Bee Soh, Belinda Qin Pei Foo, Zheng Jye Ling, James Luen Wei Yip, Sreemanee Raaj Dorajoo","doi":"10.1007/s40264-025-01525-w","DOIUrl":"https://doi.org/10.1007/s40264-025-01525-w","url":null,"abstract":"<p><strong>Introduction: </strong>Transformer-based large language models (LLMs) have transformed the field of natural language processing and led to significant advancements in various text processing tasks. However, the applicability of these LLMs in identifying related drug-adverse event (AE) pairs within clinical context may be limited by the prevalent use of non-standard sentence structures and grammar.</p><p><strong>Method: </strong>Nine transformer-based LLMs pre-trained on biomedical domain corpora are fine-tuned on annotated data (n = 5088) to classify drug-AE pairs in unstructured discharge summaries as causally related or unrelated. These LLMs are then validated on text segments from deidentified hospital discharge summaries from Singapore (n = 1647). To assess generalisability, the models are validated on annotated segments (n = 4418) from the Medical Information Mart for Intensive Care (MIMIC-III) database. Performance of LLMs in identifying related drug-AE pairs is then compared against a prior benchmark set by traditional machine learning models on the same data.</p><p><strong>Results: </strong>Using an LLM-Bidirectional long short-term memory (LLM-BiLSTM) architecture, transformer-based LLMs improve F1 score as compared to prior benchmark with BioM-ELECTRA-Large-BiLSTM showing an average F1 score improvement of 16.1% (increase from 0.64 to 0.74). Applying additional rules on the LLM-based predictions, like ignoring drug-AE pairs when the AE is a known indication of the drug, results in a further reduction in false positive rates with precision increases of up to 5.6% (0.04 increment).</p><p><strong>Conclusion: </strong>Transformer-based LLMs outperform traditional machine learning methods in identifying causally related drug-AE pairs embedded within unstructured discharge summaries. Nonetheless the improvement in performance with rules indicates that LLMs still possess some degree of imperfection for this causal relation detection task.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467319","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":"Pharmacogenetic Testing in the Outpatient Setting in Switzerland: A Descriptive Study Using Swiss Claims Data.","authors":"Nina L Wittwer, Christoph R Meier, Carola A Huber, Henriette E Meyer Zu Schwabedissen, Samuel Allemann, Cornelia Schneider","doi":"10.1007/s40264-025-01522-z","DOIUrl":"https://doi.org/10.1007/s40264-025-01522-z","url":null,"abstract":"<p><strong>Background: </strong>In Switzerland, consumers are exposed to drugs with pharmacogenetic (PGx) recommendations in 78% of cases. Pre-emptive PGx testing for seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fluorouracil, capecitabine, and irinotecan) has been covered by basic health insurance since 2017. PGx testing for other drugs is only covered if it is reactive and prescribed by a clinical pharmacologist. No data are yet available on the implementation of PGx testing in the outpatient setting.</p><p><strong>Aim: </strong>The objective of this study was to determine the prevalence of ambulatory PGx testing in the Swiss population, to characterize PGx-tested individuals, and to identify the most commonly used drugs before and after PGx testing.</p><p><strong>Methods: </strong>We assessed the prevalence of PGx testing in Switzerland and characterized individuals who underwent PGx testing between 2017 and 2021 using claims data from a large health insurance company.</p><p><strong>Results: </strong>Of 894,748 individuals registered for the entire study period, only 817 (0.09%) underwent PGx testing. Those who underwent PGx testing were more frequently female and claimed more drugs and PGx drugs than those who did not undergo PGx testing. The drugs used before and after PGx testing differed, and fewer drugs with reimbursement for pre-emptive PGx testing were included before PGx testing.</p><p><strong>Conclusion: </strong>In Switzerland, personalized pharmacotherapy has the potential to be improved, as only 0.09% of the studied population underwent PGx testing, despite 77.4% claiming PGx drugs.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457122","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":"Leveraging FDA Labeling Documents and Large Language Model to Enhance Annotation, Profiling, and Classification of Drug Adverse Events with AskFDALabel.","authors":"Leihong Wu, Hong Fang, Yanyan Qu, Joshua Xu, Weida Tong","doi":"10.1007/s40264-025-01520-1","DOIUrl":"https://doi.org/10.1007/s40264-025-01520-1","url":null,"abstract":"<p><strong>Background: </strong>Drug adverse events (AEs) represent a significant public health concern. US Food and Drug Administration (FDA) drug labeling documents are an essential resource for studying drug safety such as assessing a drug's likelihood to cause certain organ toxicities; however, the manual extraction of AEs is labor-intensive, requires specialized expertise, and is challenging to maintain, due to frequent updates of the labeling documents.</p><p><strong>Objective: </strong>To automate the extraction of AE data from FDA drug labeling documents, we developed a workflow based on AskFDALabel, a large language model (LLM)-powered framework, and its demonstration in drug safety studies.</p><p><strong>Methods: </strong>This framework incorporates a retrieval-augmented generation (RAG) component based on FDALabel to enhance standard LLM inference. Key steps include (1) selection of a task-specific template, (2) FDALabel database querying, and (3) content preparation for LLM processing. We evaluated the performance of the framework in three benchmark experiments, including drug-induced liver injury (DILI) classification, drug-induced cardiotoxicity (DICT) classification, and AE term recognition.</p><p><strong>Results: </strong>AskFDALabel achieved F1-scores of 0.978 for DILI, 0.931 for DICT, and 0.911 for AE annotation, outperforming other traditional methods. It also provided cited labeling content and detailed explanations, facilitating manual verification.</p><p><strong>Conclusion: </strong>AskFDALabel exhibited high consistency with human AE annotation, particularly in classifying and profiling DILI and DICT. Thus, it can significantly enhance the efficiency and accuracy of AE annotation, with promising potential for advanced AE surveillance and drug safety research.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467320","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":"Aggregation of Adverse Event Terms for Signal Detection and Labeling in Clinical Trials.","authors":"Richard C Zink, Rebecca Lyzinski, Geoffrey Mann","doi":"10.1007/s40264-025-01518-9","DOIUrl":"https://doi.org/10.1007/s40264-025-01518-9","url":null,"abstract":"<p><p>The Medical Dictionary for Regulatory Activities (MedDRA) was developed in the mid-to-late 1990s to address the shortcomings of other medical dictionaries used for coding adverse events. Since that time, MedDRA has become the required coding dictionary for major regulatory authorities involved with the International Council for Harmonisation. Due to the increased specificity and significant increase in terminology over time, several approaches have been developed to aggregate terms for the purposes of signal detection and labeling. We present the approaches taken and suggested to date to aggregate preferred terms into meaningful medical concepts. We discuss the pros and cons of different methods in which to group terms, and illustrate that analyses performed for MedDRA preferred terms can also be conducted using aggregated terms. However, some features of adverse events available at the preferred term level, such as severity and relationship to study therapy, require additional consideration for analysis. In the last 25 years, the pendulum for medical coding is swinging in the other direction. Faced with a deluge of preferred terms, users of MedDRA are developing new ways in which to collapse terms into medical concepts. The ability to identify safety concerns and communicate important data in drug labels effectively and consistently are at risk, particularly with the introduction of new aggregations.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425185","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}