Drug Safety最新文献

{"title":"Temporal Changes in Reporting of Neurodevelopmental Outcomes After Maternal Exposure to Valproate: A Contribution of the ConcePTION Project.","authors":"Dimitra Gkolfi, Yrea R J van Rijt-Weetink, Henric Taavola-Gustafsson, Lovisa Sandberg, Boukje C Raemaekers, Florence P A M van Hunsel, Anneke L M Passier, Rebecca L Bromley, Laura M Yates, Eugène P van Puijenbroek","doi":"10.1007/s40264-025-01583-0","DOIUrl":"https://doi.org/10.1007/s40264-025-01583-0","url":null,"abstract":"<p><strong>Background: </strong>Understanding changes over time in the quantity and characteristics of reports submitted to pharmacovigilance centres is crucial for accurately interpreting safety signals associated with exposure during pregnancy.</p><p><strong>Objective: </strong>We aimed to assess temporal changes in the outcome measures for signal detection, specifically the number and clustering of reported adverse events concerning maternal valproate exposure and neurodevelopmental outcomes in offspring.</p><p><strong>Methods: </strong>An observational study using VigiBase analysed changes in the number of reports and event clustering related to neurodevelopmental outcomes in offspring following valproate exposure during pregnancy. Reports from the start of VigiBase till 3 April, 2023 were identified using the VigiBase pregnancy algorithm. Time trend graphs illustrated reporting behavioural changes, with particular focus on the impact of major scientific publications and regulatory decisions. Report clusters, identified by the vigiGroup method, were randomised and independently reviewed by three qualified reviewers for clinical relevance to neurodevelopmental outcomes, morphological disorders or other entities.</p><p><strong>Results: </strong>Over time, an increase in reports mentioning neurodevelopmental outcomes and a more diverse pattern of adverse events for valproate has been reported. An increase in the number of reports following key publications and international regulatory guidelines was visible.</p><p><strong>Conclusions: </strong>Our study revealed an increase over time in reporting and awareness of neurodevelopmental outcomes and valproate exposure during pregnancy, following important publications and regulatory decisions. However, the extent to which these developments contributed to the observed increase remains unclear.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583409","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":"The Effect of Opioid Agonist Treatment on Injection-Related Sequelae: A Population-Based Observational Study.","authors":"Jihoon Lim, Julie Bruneau, Robert W Platt, Dimitra Panagiotoglou","doi":"10.1007/s40264-025-01574-1","DOIUrl":"https://doi.org/10.1007/s40264-025-01574-1","url":null,"abstract":"<p><strong>Introduction: </strong>Opioid agonist treatment (OAT) reduces drug-related poisonings and injection-related infections among people with opioid use disorder (OUD). Despite buprenorphine-naloxone (BNX) and methadone (MET) both being first-line OAT options in Canada, their comparative effectiveness in preventing recurrent injection-related infections and poisonings remains unclear.</p><p><strong>Objectives: </strong>This study compared the effectiveness of buprenorphine-naloxone and methadone in reducing recurrent risks of injection-related bacterial infections and opioid-related poisoning among people on OAT.</p><p><strong>Methods: </strong>We used administrative health data from Québec, Canada to create our cohort of adult patients (aged 18-65 years) on OAT maintenance between 2014 and 2019. We applied a time-dependent Cox proportional hazards model for our time-varying exposure definition to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the recurrent risks of injection-related bacterial infections and opioid-related poisoning, adjusting for age, sex, socio-demographic, and clinical factors. We also compared the effectiveness of buprenorphine-naloxone and methadone during the OAT induction phase (i.e., first 30 days of treatment).</p><p><strong>Results: </strong>The study population included 2010 patients (mean age: 41.21 years, 67.41% male). Compared to methadone, buprenorphine-naloxone was associated with 45% lower recurrent risk of opioid-related poisoning (HR: 0.55; 95% CI 0.35-0.86). Overall, the association between buprenorphine-naloxone and recurrent risk of injection-related bacterial infections suggested a weak protective effect (HR: 0.80; 95% CI 0.59-1.09). During the induction phase, there was limited evidence of differences between buprenorphine-naloxone and methadone for the recurrent risks of injection-related bacterial infections (HR: 0.91; 95% CI 0.51-1.60) and opioid-related poisoning (HR: 1.07; 95% CI 0.51-2.24).</p><p><strong>Conclusion: </strong>Among patients in OAT maintenance, buprenorphine-naloxone was associated with lower risk of recurrent opioid-related poisoning compared to methadone, but not for injection-related infections. This advantage was not observed during induction, suggesting the need for improved treatment retention early in OAT.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552648","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":"Obituary Ronald Meyboom: A Professional Life Devoted to Pharmacovigilance.","authors":"Toine Egberts, Eugene van Puijenbroek, Bert Leufkens","doi":"10.1007/s40264-025-01577-y","DOIUrl":"https://doi.org/10.1007/s40264-025-01577-y","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539553","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":"Signals of Adverse Reactions to Herbal Medicines: Evidence and Document Analysis Based on a Scoping Review.","authors":"Daniele Sartori, Jeffrey K Aronson, Judith S Brand, Oskar Gauffin, Sara Hedfors Vidlin, G Niklas Norén, Igho J Onakpoya","doi":"10.1007/s40264-025-01580-3","DOIUrl":"https://doi.org/10.1007/s40264-025-01580-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;To date, signals of adverse reactions to herbal medicines have not been systematically reviewed, limiting pharmacovigilance of herbal medicines because of a lack of data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;We sought to analyse the available evidence on signals involving herbal medicines and to determine to what extent they had been documented at the European Union (EU) level and in the USA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used the results of a published scoping review of interventional and non-interventional studies that reported signals of adverse reactions to drugs. We assigned Anatomical Therapeutic Chemical classification to all drugs, and identified herbal medicines when they fell under the  Anatomical Therapeutic Chemical V90. We ascertained the presence of the adverse reaction, or related adverse reactions, for each signal in reference documents for healthcare professionals: the US Botanical Safety Handbook and the EU monographs and US Dietary Supplement Fact Sheets; and in those for consumers: the US Dietary Supplement Label Database. We summarised the data descriptively, treating US documents as one and comparing harms across pairs of US and EU documents by signal. Documents were deemed concordant if they both included the same or related adverse reactions, or if neither did. We also compared adverse reactions across US documents for healthcare professionals with those for consumers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the 10,861 signals covered by the scoping review, 53 (0.49%) concerned herbal medicines, all based on case reports. Reference documents from both the US and EU were available for 37 signals. Most of the documents were concordant (73%), and ten (27%) were discordant: six adverse reactions were mentioned only in US documents, three only in EU monographs, and one was warned against in US documents but not in EU documents. Twenty-one signals could be followed up in the Botanical Safety Handbook and Dietary Supplement Fact Sheets. Most (68%) US documents for healthcare professionals were concordant. When the Botanical Safety Handbook and Dietary Supplement Fact Sheets did not include an adverse reaction, neither did the Dietary Supplement Label Database. However, when they did, only 20% of the labels for consumers did too. The proportion of labels mentioning adverse reactions otherwise available in documents intended for healthcare professionals ranged widely, reflecting differences across multiple labels for the same products.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Very few signals of adverse reactions from the wider scoping review concerned herbal medicines, and were all based on case reports. Information was mostly concordant across documents in the EU and USA. As manufacturers are solely responsible for the contents of the Dietary Supplement Label Database, regulatory oversight may be required to ensure that consistent and comprehensive information on the harms of herbal medicines is made avai","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539554","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":"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":"753-765"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174299/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QT Interval, Antipsychotics and Correlates Among Patients with Schizophrenia: Cross-Sectional Data from the Multicentric Real-World FACE-SZ.","authors":"Mona Gerentes, Mohamed Lajnef, Andrei Szöke, Bruno Aouizerate, Fabrice Berna, Maud Cléry, Isabelle Chéreau, Nathalie Coulon, Julia Clauss-Kobayashi, Eric Fakra, Jean-Michel Dorey, Caroline Dubertret, Guillaume Fond, Ophélia Godin, Tudi Goze, Christophe Lançon, Marion Leboyer, Sylvain Leignier, Pierre-Michel Llorca, Jasmina Mallet, David Misdrahi, Nicolas Oriol, Romain Rey, Paul Roux, Benoit Schorr, Mathieu Urbach, Etienne Véry, Franck Schürhoff, Baptiste Pignon","doi":"10.1007/s40264-025-01526-9","DOIUrl":"10.1007/s40264-025-01526-9","url":null,"abstract":"<p><strong>Background: </strong>The life expectancy of patients with schizophrenia is reduced, partly due to cardiovascular diseases. Antipsychotics are associated with QT interval prolongation, which is a risk factor for arrhythmia and cardiac arrest. The differences between antipsychotic with regard to QT interval prolongation are not well understood.</p><p><strong>Objective: </strong>The aim was to compare the QT values associated with different antipsychotics within a real-world population of subjects with clinically stable forms of schizophrenia.</p><p><strong>Methods: </strong>The FACE-SZ cohort comprises subjects with psychotic disorders, referred to schizophrenia expert cents. QT interval was measured, as well as all treatments (psychotropic and others). The following maintenance treatment for schizophrenia was analysed cross-sectionally: aripiprazole, clozapine, haloperidol, amisulpride, olanzapine, quetiapine, risperidone. Age, sex, smoking status, body mass index, blood potassium levels, and the co-prescription of another QT-prolonging treatment were used as adjustment factors in multivariable linear regression analyses.</p><p><strong>Results: </strong>Among 792 patients, the mean corrected QT (QTc) interval in the sample of patients under monotherapy was 407 ms. The mean age was 31.7 years, and the majority were male (73.3 %). In comparison to the rest of the sample, clozapine was associated with a longer QTc interval (β = 0.012, 95% CI [0.006-0.018]), while aripiprazole was significantly associated with a shorter QTc interval (β = - 0.010, 95% CI [- 0.016 to - 0.005]). Other antipsychotics were not associated with significant variations of the QTc.</p><p><strong>Conclusions: </strong>The prescription of antipsychotics should always be accompanied by close monitoring of the QTc interval to prevent the risk of severe cardiac arrhythmia, particularly concerning clozapine.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"739-752"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633824","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":"Strategies and Challenges in Coding Ambiguous Information Using MedDRA^®: An Exploration Among Norwegian Pharmacovigilance Officers.","authors":"Tahmineh Garmann, Hilde Samdal, Daniele Sartori, David Jahanlu, Fredrik Andersen, Elena Rocca","doi":"10.1007/s40264-025-01573-2","DOIUrl":"https://doi.org/10.1007/s40264-025-01573-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The Medical Dictionary for Regulatory Activities (MedDRA&lt;sup&gt;®&lt;/sup&gt;) is an international standardized medical terminology used to code various types of medical information, including safety reports of suspected adverse reactions to medicines. Quantitative studies have highlighted varying levels of coding inconsistency across MedDRA&lt;sup&gt;®&lt;/sup&gt;-relevant platforms, though the possible grounds of such inconsistency remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;We explored the reasoning and strategies employed by pharmacovigilance officers when coding selected ambiguous adverse events to MedDRA&lt;sup&gt;®&lt;/sup&gt;, categorized the types of coding inconsistencies, and explored sources of the inconsistencies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Pharmacovigilance officers from the Norwegian public health sector were invited to participate in a survey-based, cross-sectional study followed by focus group interviews. The survey consisted of 11 coding tasks, with varying degrees of ambiguity, purposively sampled from the Norwegian pharmacovigilance registry. Participants selected the appropriate MedDRA&lt;sup&gt;®&lt;/sup&gt; terms and graded the difficulty level of each task on a scale from 1 (least difficult) to 4 (most difficult). Terms selected by participants were compared with a Standard Term Selection (STS), agreed upon by the authors in consultation with a MedDRA&lt;sup&gt;®&lt;/sup&gt; trainer. Inconsistencies with the STS were classified as omission (missing term), substitution (extra term selected in the presence of an omission), and addition (extra term selected and none omitted). In focus groups, participants discussed challenges in the coding tasks and the strategies they used to overcome them. Interview transcripts were analyzed using thematic analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 26 coders (79% of the eligible population) completed the survey. Of the survey answers, 36% were identical to the STS; answers consistent with the STS varied across the specific coding tasks and did not align with the perceived difficulty of the tasks. The most common inconsistency (30% of the survey answers) arose from substituting one of multiple MedDRA&lt;sup&gt;®&lt;/sup&gt; terms. Of the survey answers, 18% included omissions without substitutions, and 6% added unnecessary terms to the STS. Eight of the 26 coders (31%) participated in the focus group interviews. Focus group themes revealed that substitutions were explained by difficulties in translating lay language to medical terminology, finding accurate English translations for Norwegian medical terms, and fitting complex descriptions into MedDRA&lt;sup&gt;®&lt;/sup&gt; terms. This was explained by themes related to ambiguity-resolution strategies. Themes explaining omissions included strategies for resolving ambiguity, contextual thinking, causal and pharmacological reasoning in the coding process, and information categorization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Tailored training programs and clear institutiona","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539555","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":"Off-the-Shelf Large Language Models for Causality Assessment of Individual Case Safety Reports: A Proof-of-Concept with COVID-19 Vaccines.","authors":"Andrea Abate, Elisa Poncato, Maria Antonietta Barbieri, Greg Powell, Andrea Rossi, Simay Peker, Anders Hviid, Andrew Bate, Maurizio Sessa","doi":"10.1007/s40264-025-01531-y","DOIUrl":"10.1007/s40264-025-01531-y","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated the feasibility of ChatGPT and Gemini, two off-the-shelf large language models (LLMs), to automate causality assessments, focusing on Adverse Events Following Immunizations (AEFIs) of myocarditis and pericarditis related to COVID-19 vaccines.</p><p><strong>Methods: </strong>We assessed 150 COVID-19-related cases of myocarditis and pericarditis reported to the Vaccine Adverse Event Reporting System (VAERS) in the United States of America (USA). Both LLMs and human experts conducted the World Health Organization (WHO) algorithm for vaccine causality assessments, and inter-rater agreement was measured using percentage agreement. Adherence to the WHO algorithm was evaluated by comparing LLM responses to the expected sequence of the algorithm. Statistical analyses, including descriptive statistics and Random Forest modeling, explored case complexity (e.g., string length measurements) and factors affecting LLM performance and adherence.</p><p><strong>Results: </strong>ChatGPT showed higher adherence to the WHO algorithm (34%) compared to Gemini (7%) and had moderate agreement (71%) with human experts, whereas Gemini had fair agreement (53%). Both LLMs often failed to recognize listed AEFIs, with ChatGPT and Gemini incorrectly identifying 6.7% and 13.3% of AEFIs, respectively. ChatGPT showed inconsistencies in 8.0% of cases and Gemini in 46.7%. For ChatGPT, adherence to the algorithm was associated with lower string complexity in prompt sections. The random forest analysis achieved an accuracy of 55% (95% confidence interval: 35.7-73.5) for predicting adherence to the WHO algorithm for ChatGPT.</p><p><strong>Conclusion: </strong>Notable limitations of ChatGPT and Gemini have been identified in their use for aiding causality assessments in vaccine safety. ChatGPT performed better, with higher adherence and agreement with human experts. In the investigated scenario, both models are better suited as complementary tools to human expertise.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"805-820"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613979","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":"Mitigation and Management of Common Toxicities Associated with the Administration of CAR-T Therapies in Oncology Patients.","authors":"Jonathan Renninger, Lisa Kurz, Heather Stein","doi":"10.1007/s40264-025-01538-5","DOIUrl":"10.1007/s40264-025-01538-5","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapies are one of the main approaches among targeted cellular therapies. Despite the potential benefit and durable responses observed in some patients receiving CAR-T therapies, serious and potentially fatal toxicities remain a major challenge. The most common CAR-T-associated toxicities include cytokine release syndrome (CRS), neurotoxicity, cytopenias, and infections. While CRS and neurotoxicity are generally managed with tocilizumab and corticosteroids, respectively, high-grade toxicities can be life-threatening. Close postinfusion monitoring and assessment of clinical laboratory parameters, patient-related and clinical risk factors (e.g., age, tumor burden, comorbidities, baseline laboratory parameters, and underlying abnormalities), and therapy-related risk factors (e.g., CAR-T type, dose, and CAR-T-induced toxicity) are effective strategies to mitigate the toxicities. Clinical laboratory parameters, including various cytokines, have been identified for CRS (interleukin [IL]-1, IL-2, IL-5, IL-6, IL-8, IL-10, C-reactive protein [CRP], interferon [IFN]-γ, ferritin, granulocyte-macrophage colony-stimulating factor [GM-CSF], and monocyte chemoattractant protein-1), neurotoxicity (IL-1, IL-2, IL-6, IL-15, tumor necrosis factor [TNF]-α, GM-CSF, and IFN-γ), cytopenias (IL-2, IL-4, IL-6, IL-10, IFN-γ, ferritin, and CRP), and infections (IL-8, IL-1β, CRP, IFN-γ, and procalcitonin). CAR-T-associated toxicities can be monitored and treated to mitigate the risk to patients. Assessment of alterations in clinical laboratory parameter values that are correlated with CAR-T-associated toxicities may predict development and/or severity of a given toxicity, which can improve patient management strategies and ultimately enable the patients to better tolerate these therapies.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"719-737"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662865","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":"Using Mixed Methods to Evaluate Risk Minimisation Programs in Europe and the USA: An Innovative Blueprint.","authors":"Meredith Y Smith, Rachel Davis, Priya Bahri, Delphine Saragoussi, Viviana Nguyen, Gita A Toyserkani, Alison Hamilton","doi":"10.1007/s40264-025-01533-w","DOIUrl":"10.1007/s40264-025-01533-w","url":null,"abstract":"<p><strong>Background: </strong>Significant methodological shortcomings have been documented to date in risk minimisation program evaluations for medicinal products, including overreliance on survey methods alone. Recently updated guidances from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommend the use of frameworks and mixed methods designs to improve the rigor of these assessments.</p><p><strong>Objective: </strong>The purpose of this paper was to exemplify how a mixed methods approach, guided by an implementation science framework, can be used to design the evaluation of a risk minimisation program.</p><p><strong>Methods: </strong>We selected the Practical, Robust, Implementation and Sustainability Model (PRISM) as the implementation science framework to guide our mixed methods approach. PRISM provides a comprehensive and systematic approach to measuring the key domains relevant to the implementation and outcomes of a risk minimisation program. We mapped the PRISM domains to the evaluation dimensions described in the EMA and FDA guidances. We then specified a mixed methods evaluation design and data collection methods using a fictitious risk minimisation program as a case study for illustrative purposes.</p><p><strong>Results: </strong>On the basis of our case study, we developed quantitative and qualitative measures, including specific items for surveys and interviews, for both formative and summative evaluations. For both the formative and summative evaluations, measures focussed on assessing (1) contextual factors that could affect program implementation and impact and (2) outcomes including implementability and acceptability as well as degree of program reach, adoption, implementation, effectiveness and maintenance.</p><p><strong>Conclusions: </strong>Mixed methods, guided by a well-established implementation science framework, can be applied to ensure comprehensive formative and summative evaluations that provide fit-for-purpose information that may inform regulatory decision-making.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"821-838"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613981","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}