Drug Safety最新文献

{"title":"Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy.","authors":"Eric B Cohen, Arie Regev, Anju Garg, Adrian M Di Bisceglie, James H Lewis, John M Vierling, Judith Hey-Hadavi, Klaudia Steplewski, Anna Fettiplace, Chunlin L Chen, Nonko Pehlivanov, Stuart Kendrick, Mark I Avigan","doi":"10.1007/s40264-024-01399-4","DOIUrl":"10.1007/s40264-024-01399-4","url":null,"abstract":"<p><p>Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker-positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"321-332"},"PeriodicalIF":4.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729306","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":"Comment on \"Serially Combining Epidemiological Designs Does Not Improve Overall Signal Detection in Vaccine Safety Surveillance\".","authors":"Wan-Ting Huang, Robert T Chen, Caroline Cassard","doi":"10.1007/s40264-024-01410-y","DOIUrl":"10.1007/s40264-024-01410-y","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"401-402"},"PeriodicalIF":4.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027707","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":"Drug-Gene Risk Stratification in Patients with Suspected Drug-Induced Interstitial Lung Disease.","authors":"Marjolein Drent, Petal A Wijnen, Naomi T Jessurun, Ankie M Harmsze, Otto Bekers, Aalt Bast","doi":"10.1007/s40264-024-01400-0","DOIUrl":"10.1007/s40264-024-01400-0","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary toxicity has been associated with drug use. This is often not recognized in clinical practice, and underestimated.</p><p><strong>Objective: </strong>We aimed to establish whether polymorphisms in certain genes corresponding with a metabolic pathway of drug(s) used are associated with pulmonary toxicity in patients with suspected drug-induced interstitial lung disease (DI-ILD).</p><p><strong>Methods: </strong>This retrospective observational study explored genetic variations in three clinically relevant cytochrome P450 (CYP) iso-enzymes (i.e., CYP2D6, CYP2C9, and CYP2C19) in a group of patients with a fibroticinterstitial lung disease, either non-specific interstitial pneumonia (n = 211) or idiopathic pulmonary fibrosis (n = 256), with a suspected drug-induced origin.</p><p><strong>Results: </strong>Of the 467 patients, 79.0% showed one or more polymorphisms in the tested genes accompanied by the use of drug(s) metabolized by a corresponding affected metabolic pathway (60.0% poor metabolizers and/or using two or more drugs [likely DI-ILD], 37.5% using three or more [highly likely DI-ILD]). Most commonly used drugs were statins (63.1%) with a predominance among men (69.4 vs 47.1%, p < 0.0001). Nitrofurantoin, not metabolized by the tested pathways, was prescribed more frequently among women (51.9 vs 4.5%, p < 0.00001).</p><p><strong>Conclusions: </strong>In our cohort with suspected DI-ILD, 79% carried one or more genetic variants accompanied by the use of drugs metabolized by a corresponding affected pathway. In 60%, the diagnosis of DI-ILD was likely, whereas in 37.5%, it was highly likely, based on CYP analyses. This study underlines the importance of considering both drug use and genetic make-up as a possible cause, or at least a contributing factor, in the development and/or progression of fibrotic lung diseases.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT00267800, registered in 2005.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"355-363"},"PeriodicalIF":4.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068261","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":"An 8-Year Prospective, Observational, Multi-centre Post-Marketing Safety Surveillance Study Conducted in South Korea (2014-2022) Following the Introduction of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine (Fluarix Tetra) for Subjects Aged 6 Months and Older.","authors":"Gaël Dos Santos, Raghavendra Devadiga, Chun Soo Kim, Joon Bang","doi":"10.1007/s40264-024-01395-8","DOIUrl":"10.1007/s40264-024-01395-8","url":null,"abstract":"<p><strong>Introduction: </strong>Seasonal influenza is associated with substantial public health burden. The objective of this study was to assess the safety of inactivated quadrivalent seasonal influenza vaccine (IIV4, Fluarix Tetra, GSK, Belgium) in subjects aged ≥ 6 months in Korea.</p><p><strong>Methods: </strong>This prospective, observational, non-comparative, multi-centre post-marketing surveillance study was conducted in Korea in subjects aged ≥ 3 years for 6 years (2014-2020) and extended to subjects aged 6-35 months for 4 years (2018-2022). Subjects received IIV4 in routine clinical practice according to local prescribing information. Adverse events (AEs) were recorded over 21 days post-vaccination.</p><p><strong>Results: </strong>The group aged ≥ 3 years included 701 subjects (mean 31.97 years, range 3-86 years, 46.36% male), and the group aged 6-35 months included 687 subjects (mean 16.31 months, 47.02% male). In the group aged ≥ 3 years, 98 subjects (13.98%) reported 140 AEs, of which 42 events in 34 subjects (4.85%) were adverse reactions to vaccine (ARVs). Most of the ARVs were expected, mainly administration site reactions. There were seven mild unexpected ARVs. In the group aged 6-35 months, 248 AEs were reported in 149/687 subjects (21.69%). ARVs were reported in 25/687 subjects (3.64%, 29 events); one was considered unexpected. There were five serious AEs overall, none of which were considered related.</p><p><strong>Conclusion: </strong>No safety concerns were found during this surveillance study of IIV4 in subjects aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated for use in all age groups with a vaccine indication.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"365-375"},"PeriodicalIF":4.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131053","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":"Authors' Response to Huang et al.'s Comment on \"Serially Combining Epidemiological Designs Does Not Improve Overall Signal Detection in Vaccine Safety Surveillance\".","authors":"Fan Bu, Faaizah Arshad, George Hripcsak, Patrick B Ryan, Martijn J Schuemie, Marc A Suchard","doi":"10.1007/s40264-024-01411-x","DOIUrl":"10.1007/s40264-024-01411-x","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"403-404"},"PeriodicalIF":4.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027706","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":"Risk Factors Associated with Medication Administration Errors in Children: A Prospective Direct Observational Study of Paediatric Inpatients","authors":"Johanna I. Westbrook, Ling Li, Amanda Woods, Tim Badgery-Parker, Virginia Mumford, Alison Merchant, Erin Fitzpatrick, Magdalena Z. Raban","doi":"10.1007/s40264-024-01408-6","DOIUrl":"https://doi.org/10.1007/s40264-024-01408-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Limited evidence exists regarding medication administration errors (MAEs) on general paediatric wards or associated risk factors exists.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The aim of this study was to identify nurse, medication, and work-environment factors associated with MAEs among paediatric inpatients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This was a prospective, direct observational study of 298 nurses in a paediatric referral hospital in Sydney, Australia. Trained observers recorded details of 5137 doses prepared and administered to 1530 children between 07:00 h and 22:00 h on weekdays and weekends. Observation data were compared with medication charts to identify errors. Clinical errors, potential severity and actual harm were assessed. Nurse characteristics (e.g. age, sex, experience), medication type (route, high-risk medications, use of solvent/diluent), and work variables (e.g. time of administration, weekday/weekend, use of an electronic medication management system [eMM], presence of a parent/carer) were collected. Multivariable models assessed MAE risk factors for any error, errors by route, potentially serious errors, and errors involving high-risk medication or causing actual harm.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Errors occurred in 37.0% (<i>n</i> = 1899; 95% confidence interval [CI] 35.7–38.3) of administrations, 25.8% (<i>n</i> = 489; 95% CI 23.8–27.9) of which were rated as potentially serious. Intravenous infusions and injections had high error rates (64.7% [<i>n</i> = 514], 95% CI 61.3–68.0; and 77.4% [<i>n</i> = 188], 95% CI 71.7–82.2, respectively). For intravenous injections, 59.7% (95% CI 53.4–65.6) had potentially serious errors. No nurse characteristics were associated with MAEs. Intravenous route, early morning and weekend administrations, patient age ≥ 11 years, oral medications requiring solvents/diluents and eMM use were all significant risk factors. MAEs causing actual harm were 45% lower using an eMM compared with paper charts.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Medication error prevention strategies should target intravenous administrations and not neglect older children in hospital. Attention to nurses’ work environments, including improved design and integration of medication technologies, is warranted.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":"35 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140036107","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":"An Overview of Regression Models for Adverse Events Analysis.","authors":"Elsa Coz, Mathieu Fauvernier, Delphine Maucort-Boulch","doi":"10.1007/s40264-023-01380-7","DOIUrl":"10.1007/s40264-023-01380-7","url":null,"abstract":"<p><p>Over the last few years, several review articles described the adverse events analysis as sub-optimal in clinical trials. Indeed, the context surrounding adverse events analyses often imply an overwhelming number of events, a lack of power to find associations, but also a lack of specific training regarding those complex data. In randomized controlled trials or in observational studies, comparing the occurrence of adverse events according to a covariable of interest (e.g., treatment) is a recurrent question in the analysis of drug safety data, and adjusting other important factors is often relevant. This article is an overview of the existing regression models that may be considered to compare adverse events and to discuss model choice regarding the characteristics of the adverse events of interest. Many dimensions may be relevant to compare the adverse events between patients, (e.g., timing, recurrence, and severity). Recent efforts have been made to cover all of them. For chronic treatments, the occurrence of intercurrent events during the patient follow-up usually needs the modeling approach to be adapted (at least with regard to their interpretation). Moreover, analysis based on regression models should not be limited to the estimation of relative effects. Indeed, absolute risks stemming from the model should be presented systematically to help the interpretation, to validate the model, and to encourage comparison of studies.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"205-216"},"PeriodicalIF":4.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440514","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 Moroccan Experience of Implementing a University Curriculum for the Pharmacovigilance of Herbal Medicines (Phytovigilance).","authors":"Souad Skalli","doi":"10.1007/s40264-023-01372-7","DOIUrl":"10.1007/s40264-023-01372-7","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"285-286"},"PeriodicalIF":4.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590538","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":"International Trends in Adverse Drug Event-Related Mortality from 2001 to 2019: An Analysis of the World Health Organization Mortality Database from 54 Countries.","authors":"Toshihiro Koyama, Shunya Iinuma, Michio Yamamoto, Takahiro Niimura, Yuka Osaki, Sayoko Nishimura, Ko Harada, Yoshito Zamami, Hideharu Hagiya","doi":"10.1007/s40264-023-01387-0","DOIUrl":"10.1007/s40264-023-01387-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level.</p><p><strong>Methods: </strong>This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates.</p><p><strong>Results: </strong>The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92-3.18) in 2001 to 6.86 (95% confidence interval 5.76-7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20-50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019.</p><p><strong>Conclusions: </strong>The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"237-249"},"PeriodicalIF":4.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828687","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":"Enhancing Transparency in Defining Studied Drugs: The Open-Source Living DiAna Dictionary for Standardizing Drug Names in the FAERS.","authors":"Michele Fusaroli, Valentina Giunchi, Vera Battini, Stefano Puligheddu, Charles Khouri, Carla Carnovale, Emanuel Raschi, Elisabetta Poluzzi","doi":"10.1007/s40264-023-01391-4","DOIUrl":"10.1007/s40264-023-01391-4","url":null,"abstract":"<p><strong>Introduction: </strong>In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often overlooked. The US FDA Adverse Event Reporting System (FAERS) records drug names as free text, necessitating mapping to active ingredients. Although pre-mapped databases exist, the subjectivity and lack of transparency of the mapping process lead to a loss of control over the object of study.</p><p><strong>Objective: </strong>We implemented the DiAna dictionary, systematically mapping individual free-text instances to their corresponding active ingredients and linking them to the World Health Organization Anatomical Therapeutic Chemical (WHO-ATC) classification.</p><p><strong>Methods: </strong>We retrieved all drug names reported to the FAERS (2004-December 2022). Using existing vocabularies and string editing, we automatically mapped free text to ingredients. We manually revised the mapping and linked it to the ATC classification.</p><p><strong>Results: </strong>We retrieved 18,151,842 reports, with 74,143,411 drug entries. We manually checked the first 14,832 terms, up to terms occurring over 200 times (96.88% of total drug entries), to 6282 unique active ingredients. Automatic unchecked translations extend the standardization to 346,854 terms (98.94%). The DiAna dictionary showed a higher sensitivity compared with RxNorm alone, particularly for specific drugs (e.g., rimegepant, adapalene, drospirenone, umeclidinium). The most prominent drug classes in the FAERS were immunomodulating (37.40%) and neurologic drugs (29.19%).</p><p><strong>Conclusion: </strong>The DiAna dictionary, as a dynamic open-source tool, provides transparency and flexibility, enabling researchers to actively shape drug definitions during the mapping phase. This empowerment enhances accuracy, reproducibility, and interpretability of results.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"271-284"},"PeriodicalIF":4.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086304","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}