Drug Safety最新文献

{"title":"Post-licensure Safety Surveillance of 20-Valent Pneumococcal Conjugate Vaccine (PCV20) Among US Adults in the Vaccine Adverse Event Reporting System (VAERS).","authors":"Mayra Oliveira, Paige Marquez, Carol Ennulat, Phillip Blanc, Kerry Welsh, Narayan Nair, Monica Taminato, Pedro L Moro","doi":"10.1007/s40264-024-01498-2","DOIUrl":"10.1007/s40264-024-01498-2","url":null,"abstract":"<p><strong>Background: </strong>On June 8, 2021, a new 20-valent pneumococcal conjugate vaccine (PCV20, PREVNAR 20^®, Pfizer, Inc.) was licensed for use in adults aged ≥ 18 years by the US Food and Drug Administration (FDA).</p><p><strong>Objective: </strong>To describe reports to the Vaccine Adverse Event Reporting System (VAERS) after administration of the 20-valent pneumococcal conjugate vaccine in adults.</p><p><strong>Methods: </strong>We searched the VAERS for reports of adverse events involving persons aged ≥ 19 years who received PCV20 during October 20, 2021, through December 31, 2023. Our evaluation included automated analysis of reports, clinical review of serious reports and pre-specified events of special interest, empirical Bayesian data mining to assess for disproportionate reporting, and estimation of reporting rates for reports of Guillain-Barré syndrome (GBS).</p><p><strong>Results: </strong>The VAERS received 1976 reports after PCV20 administration in persons aged ≥ 19 years (6% of reports involved serious events). The most common adverse events among persons aged 19-64 years (n = 798) were injection-site reactions (231, 29%), pain (134, 17%), erythema (118, 15%), and fever (117, 15%). For persons aged ≥ 65 years (n = 1178), the most common adverse events were injection-site reactions (417, 35%), pain (180, 15%), pain in extremity (162, 14%), and erythema (158, 13%). A data mining alert (EB05 = 3.812) for the MedDRA Preferred Term \"Guillain-Barre syndrome\" was observed for serious reports. Clinical review verified 11 of 20 GBS reports; 7/11 vaccine recipients were aged ≥ 65 years. Among the 11 verified cases, the median time from vaccination to symptom onset was 14 days. Five persons received another vaccine on the same visit. The reporting rate of GBS after PCV20 receipt was 0.5 cases per million doses distributed. No other safety concern was identified.</p><p><strong>Conclusions: </strong>During the period of this post-licensure review of PCV20, we found most reports were non-serious and comprised mostly local and systemic (e.g., fever) reactions consistent with prelicensure studies. In serious reports, we also identified a data mining alert for GBS after receipt of PCV20, which Centers for Disease Control and Prevention and the FDA are investigating further. No other new or unexpected safety concern was identified.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"279-286"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812553","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":"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":"Views on the Development and Use of a New Digital Adverse Drug Event Reporting Platform in Australia: A Qualitative Study.","authors":"Eyob Alemayehu Gebreyohannes, Christopher Thornton, Myra Thiessen, Sieta T de Vries, Gretchen Coombs, Indae Hwang, Renly Lim","doi":"10.1007/s40264-024-01489-3","DOIUrl":"10.1007/s40264-024-01489-3","url":null,"abstract":"<p><strong>Background: </strong>Reporting of adverse drug events (ADEs) to regulatory authorities remains low, particularly among consumers.</p><p><strong>Objectives: </strong>To explore stakeholders' views on the development and use of a digital platform to improve ADE reporting by consumers to the regulatory authority in Australia, i.e., the Therapeutic Goods Administration.</p><p><strong>Methods: </strong>A qualitative study was conducted using semi-structured interviews, focus group discussions (FGDs), and co-design workshops with consumers, healthcare professionals (HCPs), and regulators. The interview recordings were transcribed verbatim, coded, and analysed thematically according to the Capability, Opportunity, Motivation, Behaviour model. Findings of the FGDs and co-design workshops were incorporated to enhance and complement the insights gathered from the interviews.</p><p><strong>Results: </strong>A total of 39 participants took part in the study (54 % consumers, 41 % HCPs, and 5 % regulators). Uncovered themes related to ADE reporting in general were: difficulty recognizing ADEs and health literacy, awareness about reporting ADEs (Capability); visibility of ADE reporting, professionals' views on consumer ADE reporting, consumer education (Opportunity); the common good, benefit to the reporter, identifying ADEs worth reporting, and concern about reporting (Motivation). Additional identified themes specific to a new digital platform were: physical abilities (Capability); features that facilitate intuitive use, convenience and accessibility, user experience, integration with existing systems, trust, sharing experiences with others (Opportunity); and concern about using a reporting platform, and feedback loop (Motivation).</p><p><strong>Conclusions: </strong>A cross-section of attitudes and values were obtained regarding ADE reporting in general and a new ADE reporting digital platform for consumers in Australia, which will inform its development, implementation and evaluation.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"179-190"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563849","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":"Incidence of Idiosyncratic Drug-Induced Liver Injury Caused by Prescription Drugs.","authors":"Vincent L Chen, Don C Rockey, Einar S Bjornsson, Huiman Barnhart, Jay H Hoofnagle","doi":"10.1007/s40264-024-01486-6","DOIUrl":"10.1007/s40264-024-01486-6","url":null,"abstract":"<p><strong>Background: </strong>The incidence of drug-induced liver injury (DILI) is not known for most prescription medications. We aimed to estimate the incidence of DILI for commonly prescribed outpatient drugs.</p><p><strong>Methods: </strong>To establish a baseline estimate of DILI incidence, we used the estimated incidence (EI) of amoxicillin/clavulanate DILI from a previous population-based study in Iceland. This was combined with the multicenter prospective DILI Network (DILIN) cohort and the US population-based Medical Expenditure Panel Survey (MEPS). From 2005 to 2019, prescription drugs with at least five bona fide DILIN cases and data from at least 10 of the 15 years from MEPS during that timeframe were included. The EI for 'drug A' was calculated as follows: <math><mrow><mtext>EI</mtext> <mrow><mo>(</mo> <mtext>drug A</mtext> <mo>)</mo></mrow> <mo>=</mo> <mtext>EI</mtext> <mfenced><mtext>AC</mtext></mfenced> <mo>×</mo> <mfrac><mrow><mo>#</mo> <mspace></mspace> <mtext>DILIN cases of drug A</mtext></mrow> <mrow><mo>#</mo> <mspace></mspace> <mtext>annual new prescriptions of drug A</mtext></mrow> </mfrac> <mo>×</mo> <mfrac><mrow><mo>#</mo> <mspace></mspace> <mtext>annual new prescriptions of AC</mtext></mrow> <mrow><mo>#</mo> <mspace></mspace> <mtext>DILIN cases of AC</mtext></mrow> </mfrac> </mrow> </math> RESULTS: In total, 30 drugs met the inclusion criteria, of which 11 were antibiotics, 4 were antiepileptic drugs (AEDs), 4 were statins, and 11 were other drug types. The highest EI was seen with azathioprine and older AEDs, with one DILI case per 349-2329 new prescriptions. The EI of antibiotics ranged greatly, with the highest risk seen for minocycline, amoxicillin/clavulanate, and nitrofurantoin (approximately 1:1000-2400 new prescriptions), and lowest risk for clindamycin, doxycycline, azithromycin, and amoxicillin (approximately 1:40,000-170,000 new prescriptions). The EI for commonly prescribed statins was approximately 1:10,000-50,000. Important medication classes with > 5 million new prescriptions from 2005 to 2019 but fewer than five DILIN cases included β-blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and metformin, which presumably have very low DILI incidence.</p><p><strong>Conclusions: </strong>The highest EI was found for azathioprine, older antiepileptics, and minocycline. In contrast, many widely used drugs are rare causes of DILI. These findings may help clinicians better weigh potential benefits of medications against hepatotoxicity risk.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"151-160"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343748","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":"Teratogenic Risk Impact and Mitigation (TRIM): Study Protocol for the Development of a Decision Support Tool to Prioritize Medications for Risk Mitigation.","authors":"Almut G Winterstein, Celeste L Y Ewig, Yanning Wang, Nicole E Smolinski, Gita A Toyserkani, Cynthia LaCivita, Leila Lackey, Sara Eggers, Esther H Zhou, Vakaramoko Diaby, Amir Sarayani, Thuy Thai, Judith C Maro, Sonja A Rasmussen","doi":"10.1007/s40264-024-01488-4","DOIUrl":"10.1007/s40264-024-01488-4","url":null,"abstract":"<p><strong>Introduction: </strong>Preventing prenatal exposure to teratogenic medications is an important goal of regulatory risk mitigation efforts. In the USA, as of March 2024, 11 teratogenic medications have a required Risk Evaluation and Mitigation Strategy (REMS) program. It is unclear whether these programs target those medications with the most significant impact on public health and adverse pregnancy outcomes.</p><p><strong>Objectives: </strong>This study aims to develop an innovative decision support tool that uses explicit, quantifiable criteria to facilitate prioritization of teratogenic medications for risk mitigation strategies.</p><p><strong>Methods: </strong>The Teratogenic Risk Impact and Mitigation (TRIM) decision support tool will be developed by a national panel via a modified Delphi approach to define measurable criteria, and a multi-criteria decision analysis to estimate criteria weights within a discrete choice experiment. The TRIM scores will then be calculated for 12 teratogenic drugs with active or eliminated REMS programs and for 12 teratogenic drugs without REMS. These drugs will be identified based on highest prenatal exposure prevalence in claims data of privately and publicly insured individuals. Data for the TRIM criteria levels for these 24 drugs will be identified from evidence searches and ad hoc analyses of the same claims data.</p><p><strong>Conclusions: </strong>Teratogenic Risk Impact and Mitigation is intended to inform regulatory decision making about the need for risk mitigation programs for teratogenic medications by providing explicit, quantifiable, evidence-based criteria. The TRIM scores of 24 teratogenic drugs may provide benchmarks for considering REMS for marketed and new teratogenic medications.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"107-117"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582335","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":"Fracture-Related Safety Reporting of JAK Inhibitors: An Analysis from the WHO Global VigiBase.","authors":"Adrian Martinez de la Torre, Andreas Bech Clausen, Andrea M Burden, Stefan Weiler","doi":"10.1007/s40264-024-01490-w","DOIUrl":"10.1007/s40264-024-01490-w","url":null,"abstract":"<p><strong>Introduction: </strong>The Janus kinase (JAK) inhibitors are treatment options for autoimmune diseases. Numerous safety concerns have been raised. The European Medicines Agency updated the product information of tofacitinib to include the risk of fractures-but not for other JAK inhibitors. We conducted a global pharmacovigilance analysis of previously investigated JAK inhibitors to investigate a potential class effect.</p><p><strong>Methods: </strong>Individual case safety reports (ICSRs) for all licensed JAK inhibitors were identified from the global WHO pharmacovigilance database. The primary outcome of interest was a bone fracture. Disproportionality analyses using reporting odds ratios (RORs) were conducted.</p><p><strong>Results: </strong>We identified 122,037 ICSRs for tofacitinib, 27,786 ICSRs for upadacitinib, 14,616 ICSRs for baricitinib, 830 for filgotinib, and 350 for abrocitinib. Among the ICSRs, we identified 2198 (1.8%), 634 (2.3%), and 144 (1.0%) reports, where a bone fracture was reported for tofacitinib, upadacitinib, and baricitinib, respectively. Few reports were available for the newest drugs filgotinib (10) and abrocitinib (1). JAK inhibitors were associated with increased reporting for fracture: tofacitinib (ROR 3.34, 95% confidence interval [CI] 3.20-3.48), upadacitinib (ROR 4.23, 95% CI 3.80-4.48), baricitinib (ROR 1.80, 95% CI 1.52-2.11) and filgotinib (ROR 2.24, 95% CI 1.11-3.94). Patients with bone fractures were more often female, older and had a higher number of co-reported medications. They were more likely to use glucocorticoids, opioids, and bisphosphonates.</p><p><strong>Conclusion: </strong>The results from this pharmacovigilance analysis, based on a spontaneous reporting database associated with inherent limitations, suggest a potential risk of fractures with JAK inhibitors, indicating that a class effect cannot be ruled out.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"191-201"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738682","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":"Investigation of the Role of Chemical Analysis in Causality Assessment of Herbal and Dietary Supplement-Induced Liver Injury.","authors":"Dina Halegoua-DeMarzio, Victor J Navarro, Ashley Davis, Jawad Ahmad, Bharathi Avula, Huiman Barnhart, A Sidney Barritt, Herbert L Bonkovsky, Vincent L Chen, Gina Choi, Robert J Fontana, Marwan S Ghabril, Ikhlas Khan, Christopher Koh, Joseph Odin, Don C Rockey, Hoss Rostami, Jose Serrano, Averell H Sherker, Andrew Stolz, Hans L Tillmann, Raj Vuppalanchi","doi":"10.1007/s40264-024-01484-8","DOIUrl":"10.1007/s40264-024-01484-8","url":null,"abstract":"<p><strong>Background: </strong> The attribution of drug-induced liver injury (DILI) to specific herbal and dietary supplements (HDS) is confounded by inaccurate labels and undisclosed ingredients. The US Drug-Induced Liver Injury Network (DILIN) determines the attribution of injury to an agent through its structured expert opinion causality assessment process, but without the use of chemical analysis data of HDS. We aimed to determine the impact of chemical analysis of HDS products on prior causality assessment scores.</p><p><strong>Methods: </strong>Obtained samples of HDS consumed by DILIN-enrolled patients were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Chemical analysis data were compared to label accuracy and detect whether the product contained botanical and non-botanical compounds. A comparison of the causality scores reassessed with chemical analysis was compared with the original scores.</p><p><strong>Results: </strong>A total of 54 previously adjudicated cases with chemical analysis available were reassessed for causality with chemical analysis data; reviewers were blinded to original causality scores. Using the chemical analysis data, 37% (n = 20) of the 54 cases were scored with a higher likelihood of DILI compared with the original causality scores; 14 of the 20 (70%) moved from probable to highly likely; 52% had no change in causality score; and 11% of cases were scored as a lower likelihood of DILI.</p><p><strong>Conclusions: </strong> Our study demonstrates that there is value in using HDS chemical analysis data in the causality assessment process for DILI. In more than a third of cases, chemical analysis of products led to an increased confidence in DILI attribution to HDS. These findings suggest that chemical analysis is an important tool in causality assessment for HDS agents, specifically in challenging situations, and further studies are needed to confirm its applicability in clinical practice.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"143-150"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361323","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":"Challenges in the Implementation of EU Risk Minimisation Measures for Medicinal Products in Clinical Practice Guidelines: Mixed Methods Multi-Case Study.","authors":"Mathias Møllebæk, Helga Gardarsdottir, Alexia-Georgia Bikou, Ana Kodrič, Ana Marta Silva, Armin Andersen, Christos Kontogiorgis, Elita Poplavska, Fariba Ahmadizar, Foteini Dermiki-Gkana, Ieva Rutkovska, Inês Ribeiro Vaz, Mitja Kos, Paula Barão, Renske Grupstra, Teresa Leonardo Alves, Anna Birna Almarsdóttir","doi":"10.1007/s40264-024-01487-5","DOIUrl":"10.1007/s40264-024-01487-5","url":null,"abstract":"<p><strong>Introduction: </strong>Risk minimisation measures (RMMs) aim to ensure safe use of medicines, but their implementation in clinical practice is complicated by the diversity of stakeholders whose clinical decision making they seek to inform. Clinical practice guidelines (CPGs) are considered integral in clinical decision making.</p><p><strong>Objectives: </strong>To determine the extent to which RMMs are included in the relevant CPGs and to describe factors that determine RMM inclusion.</p><p><strong>Methods: </strong>A multi-case study design using quantitative document analysis of CPGs combined with qualitative interviews with informants from organisations that issue CPGs. Cases from five therapeutic areas (TAs) with a regulatory requirement for further RMMs were studied individually in six EU member states (Denmark, Greece, Latvia, Netherlands, Portugal and Slovenia). Clinical practice guidelines were analysed using pre-defined coding frameworks. Interviewees were sampled purposively for experience and knowledge about CPG development and RMM inclusion. Verbatim interview transcripts were analysed inductively.</p><p><strong>Results: </strong>In total, 136 CPGs were analysed, and RMM information about TAs was included in 25% of CPGs. Based on 71 interviews we found that factors that determine RMM inclusion in CPGs include clinicians' low awareness of RMMs despite awareness of RMMs' safety concern, low expectation of RMMs' clinical utility, and unfamiliarity with pharmacovigilance data supporting RMMs and perceived incompatibility of CPGs' scope and purpose and RMM information.</p><p><strong>Conclusions: </strong>The inclusion of RMM information in relevant CPGs is remarkably limited. It may be explained by characteristics of CPGs and of RMMs as well as lack of connection between national regulators and organisations and authors developing CPGs. More collaboration between stakeholders, national regulators and the EMA may advance implementation.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"161-177"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681243","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}