Drug Safety最新文献

{"title":"A Comparison of Active Pharmacovigilance Strategies Used to Monitor Adverse Events to Antiviral Agents: A Systematic Review.","authors":"Renato Ferreira-da-Silva, Joana Reis-Pardal, Manuela Pinto, Matilde Monteiro-Soares, Bernardo Sousa-Pinto, Manuela Morato, Jorge Junqueira Polónia, Inês Ribeiro-Vaz","doi":"10.1007/s40264-024-01470-0","DOIUrl":"https://doi.org/10.1007/s40264-024-01470-0","url":null,"abstract":"<p><strong>Introduction: </strong>The safety of antiviral agents in real-world clinical settings is crucial, as pre-marketing studies often do not capture all adverse events (AE). Active pharmacovigilance strategies are essential for detecting and characterising these AE comprehensively.</p><p><strong>Objective: </strong>The aim of this study was to identify and characterise active pharmacovigilance strategies used in real-world clinical settings for patients under systemic antiviral agents, focusing on the frequency of AE and the clinical data sources used.</p><p><strong>Methods: </strong>We conducted a systematic review by searching three electronic bibliographic databases targeting observational prospective active pharmacovigilance studies, phase IV clinical trials for post-marketing safety surveillance, and interventional studies assessing active pharmacovigilance strategies, focusing on individuals exposed to systemic antiviral agents.</p><p><strong>Results: </strong>We included 36 primary studies, predominantly using Drug Event Monitoring (DEM), with a minority employing sentinel sites and registries. Human immunodeficiency virus (HIV) was the most common condition, with the majority using DEM. Within the DEM, there was a wide range of incidences of patients experiencing at least one AE, and most of these studies used one or two data sources. Sentinel site studies were less common, with two on hepatitis C virus (HCV) and one on HIV, each relying on one or two data sources. The single study using a registry focusing on HIV therapy reported using just one data source. Patient interviews were the most common data source, followed by medical records and laboratory tests. The quality of the studies was considered 'good' in 18/36, 'fair' in 1/36, and 'poor' in 17/36 studies.</p><p><strong>Conclusion: </strong>DEM was the predominant pharmacovigilance strategy, employing multiple data sources, and appears to increase the likelihood of detecting higher AE incidence. Establishing such a framework would facilitate a more detailed and consistent approach across different studies and settings.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003891","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":"Caveats of Covariate Adjustment in Disproportionality Analysis for Best Practices.","authors":"Yoshihiro Noguchi, Tomoya Tachi, Tomoaki Yoshimura","doi":"10.1007/s40264-024-01473-x","DOIUrl":"https://doi.org/10.1007/s40264-024-01473-x","url":null,"abstract":"<p><p>Spontaneous reporting systems (SRS) provide valuable data for detecting unidentified adverse events not observed in clinical trials and for conducting safety assessments that accurately reflect real-world clinical practice. With the increasing number of publications using the SRS for disproportionality analysis (DA), there is an increasing demand for a comprehensive understanding of the research limitations associated with the SRS. However, there is a lack of understanding of the caveats associated with adjusting covariates in DA of the SRS. Herein, we summarized the use of covariate adjustment and its caveats in DA. The Council for International Organizations of Medical Sciences VIII suggests considering adjustments such as stratification when they can enhance the sensitivity and/or specificity of statistical analysis. However, several database-specific and statistical caveats have been identified when adjusting for covariates derived from the SRS. Disproportionality analysis may be affected not only by reporting bias at the time of enrollment but also by sparse-data bias due to variations in the number of enrollment reports. Statistical evidence is needed to determine in which cases and to what extent sensitivity and/or specificity are affected. Nevertheless, it is important for researchers to acknowledge that certain limitations discussed in this context may be inherent and cannot be rectified. Based on this understanding, they can then make an informed decision on whether to perform a covariate adjustment.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995491","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":"Unveiling the Burden of Drug-Induced Impulsivity: A Network Analysis of the FDA Adverse Event Reporting System.","authors":"Michele Fusaroli, Stefano Polizzi, Luca Menestrina, Valentina Giunchi, Luca Pellegrini, Emanuel Raschi, Daniel Weintraub, Maurizio Recanatini, Gastone Castellani, Fabrizio De Ponti, Elisabetta Poluzzi","doi":"10.1007/s40264-024-01471-z","DOIUrl":"https://doi.org/10.1007/s40264-024-01471-z","url":null,"abstract":"<p><strong>Introduction: </strong>Impulsivity induced by dopaminergic agents, like pramipexole and aripiprazole, can lead to behavioral addictions that impact on social functioning and quality of life of patients and families (e.g., resulting in unemployment, marital problems, anxiety). These secondary effects, interconnected in networks of signs and symptoms, are usually overlooked by clinical trials, not reported in package inserts, and neglected in clinical practice.</p><p><strong>Objective: </strong>This study explores the syndromic burden of impulsivity induced by pramipexole and aripiprazole, pinpointing key symptoms for targeted mitigation.</p><p><strong>Methods: </strong>An event-event Information Component (IC) on the FDA Adverse Event Reporting System (FAERS) (January 2004 to March 2022) identified the syndrome of events disproportionally co-reported with impulsivity, separately for pramipexole and aripiprazole. A greedy-modularity clustering on composite network analyses (positive pointwise mutual information [PPMI], Ising, Φ) identified sub-syndromes. Bayesian network modeling highlighted possible precipitating events.</p><p><strong>Results: </strong>Suspected drug-induced impulsivity was documented in 7.49% pramipexole and 4.50% aripiprazole recipients. The highest IC concerned obsessive-compulsive disorder (reporting rate = 26.77%; IC median = 3.47, 95% confidence interval [CI] = 3.33-3.57) and emotional distress (21.35%; 3.42, 3.26-3.54) for pramipexole, bankruptcy (10.58%; 4.43, 4.26-4.55) and divorce (7.59%; 4.38, 4.19-4.53) for aripiprazole. The network analysis identified delusional jealousy and dopamine dysregulation sub-syndromes for pramipexole, obesity-hypoventilation and social issues for aripiprazole. The Bayesian network highlighted anxiety and economic problems as potentially precipitating events.</p><p><strong>Conclusion: </strong>The under-explored consequences of drug-induced impulsivity significantly burden patients and families. Network analyses, exploring syndromic reactions and potential precipitating events, complement traditional techniques and clinical judgment. Characterizing the secondary impact of reactions will support informed patient-centered decision making.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987691","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":"Examining the Effect of Missing Data and Unmeasured Confounding on External Comparator Studies: Case Studies and Simulations.","authors":"Gerd Rippin, Héctor Sanz, Wilhelmina E Hoogendoorn, Nicolás M Ballarini, Joan A Largent, Eleni Demas, Douwe Postmus, Theodor Framke, Lukas M Aguirre Dávila, Chantal Quinten, Francesco Pignatti","doi":"10.1007/s40264-024-01467-9","DOIUrl":"https://doi.org/10.1007/s40264-024-01467-9","url":null,"abstract":"<p><strong>Background and objective: </strong>Missing data and unmeasured confounding are key challenges for external comparator studies. This work evaluates bias and other performance characteristics depending on missingness and unmeasured confounding by means of two case studies and simulations.</p><p><strong>Methods: </strong>Two case studies were constructed by taking the treatment arms from two randomised controlled trials and an external real-world data source that exhibited substantial missingness. The indications of the randomised controlled trials were multiple myeloma and metastatic hormone-sensitive prostate cancer. Overall survival was taken as the main endpoint. The effects of missing data and unmeasured confounding were assessed for the case studies by reporting estimated external comparator versus randomised controlled trial treatment effects. Based on the two case studies, simulations were performed broadening the settings by varying the underlying hazard ratio, the sample size, the sample size ratio between the experimental arm and the external comparator, the number of missing covariates and the percentage of missingness. Thereby, bias and other performance metrics could be quantified dependent on these factors.</p><p><strong>Results: </strong>For the multiple myeloma external comparator study, results were in line with the randomised controlled trial, despite missingness and potential unmeasured confounding, while for the metastatic hormone-sensitive prostate cancer case study missing data led to a low sample size, leading overall to inconclusive results. Furthermore, for the metastatic hormone-sensitive prostate cancer study, missing data in important eligibility criteria led to further limitations. Simulations were successfully applied to gain a quantitative understanding of the effects of missing data and unmeasured confounding.</p><p><strong>Conclusions: </strong>This exploratory study confirmed external comparator strengths and limitations by quantifying the impact of missing data and unmeasured confounding using case studies and simulations. In particular, missing data in key eligibility criteria were seen to limit the ability to derive the external comparator target analysis population accurately, while simulations demonstrated the magnitude of bias to expect for various settings.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888784","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":"Author's Reply to Avó-Baião et al.'s Comment on \"Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: A Swedish Population-Based Cohort Study\".","authors":"Nele Brusselaers","doi":"10.1007/s40264-024-01463-z","DOIUrl":"10.1007/s40264-024-01463-z","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533967","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":"Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database.","authors":"Renato de Filippis, John M Kane, Elena Arzenton, Ugo Moretti, Emanuel Raschi, Gianluca Trifirò, Corrado Barbui, Pasquale De Fazio, Chiara Gastaldon, Georgios Schoretsanitis","doi":"10.1007/s40264-024-01431-7","DOIUrl":"10.1007/s40264-024-01431-7","url":null,"abstract":"<p><strong>Introduction: </strong>Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear.</p><p><strong>Methods: </strong>We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions.</p><p><strong>Results: </strong>A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9-1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1-2.5; IC 1.2, 95% CI 1.1-1.3), cyamemazine (ROR 2.3, 95% CI 1.5-3.5; IC 1.2, 95% CI 0.5-1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1-2.1; IC 0.6, 95% CI 0.1-1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%).</p><p><strong>Conclusions: </strong>Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896062","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":"Predictors of Adverse Drug Reaction-Related Hospitalisations Among People with Dementia: A Retrospective Case-Control Study.","authors":"Anum Saqib Zaidi, Gregory M Peterson, Colin M Curtain, Mohammed S Salahudeen","doi":"10.1007/s40264-024-01435-3","DOIUrl":"10.1007/s40264-024-01435-3","url":null,"abstract":"<p><strong>Introduction: </strong>Adverse drug reactions (ADRs) are common among people with dementia; however, little is known about the magnitude and predictors associated with ADR-related hospitalisation among these individuals. This study aimed to determine the magnitude, types, drugs implicated and predictors of ADRs associated with hospitalisation among people with dementia.</p><p><strong>Methods: </strong>This retrospective case-control study analysed medical records of individuals aged ≥ 65 years with dementia admitted to major public hospitals in Tasmania, Australia, from July 2010 to July 2021. Adverse drug reactions and implicated drugs were identified using administrative data and cross-checked with hospital medical records, with consensus reached among the research team.</p><p><strong>Results: </strong>Of the 7928 people admitted to hospital at least once within the study period, 1876 (23.7%) experienced at least one ADR-related hospitalisation. Of these, 300 case patients with 311 ADRs and 300 control patients were randomly selected. The most common types of ADRs were renal (acute kidney injury; AKI) (36.0%), followed by neuropsychiatric (17.6%), cardiovascular (16.0%) and haematological (13.1%). Diuretics, renin-angiotensin system (RAS) inhibitors and anti-thrombotics constituted the main implicated drug classes. The ADR-related hospitalisation was associated with: chronic kidney disease (CKD) (OR 8.00, 95% CI 2.63-24.28, p < 0.001), Australian-born (OR 1.62, 95% CI 1.08-2.43, p = 0.019), hypertension (OR 1.48, 95% CI 1.01-2.17, p = 0.044) and the number of medicines (OR 1.06, 95% CI 1.00-1.12, p = 0.022). Potentially inappropriate medication use and anticholinergic burden did not predict ADR-related hospitalisation.</p><p><strong>Conclusions: </strong>These predictors could help identify the individuals at the highest risk and enable targeted interventions to be designed.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911023","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":"Correction to: Using Social Media as a Source of Real‑World Data for Pharmaceutical Drug Development and Regulatory Decision Making.","authors":"Didrik Wessel, Nicolai Pogrebnyakov","doi":"10.1007/s40264-024-01459-9","DOIUrl":"10.1007/s40264-024-01459-9","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320736","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: \"Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: A Swedish Population-Based Cohort Study\".","authors":"Rita Avó-Baião, Raquel Vareda, Andreia Lopes","doi":"10.1007/s40264-024-01464-y","DOIUrl":"10.1007/s40264-024-01464-y","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533968","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 of Mortality Associated with Potentially Inappropriate Medication Use Including Opioids in Older Adults.","authors":"Carina D'Aiuto, Carlotta Lunghi, Line Guénette, Djamal Berbiche, Karine Bertrand, Helen-Maria Vasiliadis","doi":"10.1007/s40264-024-01429-1","DOIUrl":"10.1007/s40264-024-01429-1","url":null,"abstract":"<p><strong>Introduction and objective: </strong>As the population ages, understanding the potential risks associated with inappropriate medication use becomes increasingly important. Given the lack of studies in this area, our objective was to study the risk of mortality associated with potentially inappropriate medication use involving opioids in community-dwelling older adults.</p><p><strong>Methods: </strong>Data came from a longitudinal study on older adults aged ≥ 65 years recruited in primary care clinics between 2011 and 2013 with an average follow-up of 4.25 years. Older adults were excluded if they used an opioid or had a malignant tumor diagnosis in the year before the study survey. A nested case-control within a cohort of older adults with at least one opioid claim during follow-up was used to evaluate the risk of all-cause mortality. Four controls per case were matched on follow-up time using risk-set sampling, i.e., while still at risk of death when their matched case died. The risk of mortality was estimated using conditional logistic regression analyses. Exposure to potentially inappropriate medication use involving opioids, defined using the Beers 2019 criteria, was assessed from provincial drug claims data in the 0-90 days before death.</p><p><strong>Results: </strong>In a cohort of 472 community-dwelling older adults with an incident episode of opioid use, there were 40 cases matched to 160 controls. Exposure to inappropriate medication use involving opioids in the 90 days before death was associated with an increased risk of mortality (odds ratio 6.81, 95% confidence interval 1.69-27.47), after adjusting for potential confounders.</p><p><strong>Conclusions: </strong>Exposure to inappropriate medication use involving opioids in the 90 days before death is associated with an increased risk of mortality in older adults. These findings can be used to encourage safer pain management strategies in older adults.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896080","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}