Frontiers in Drug Safety and Regulation最新文献

{"title":"Balancing the evidence: An update on analgesic use in rheumatic and musculoskeletal diseases","authors":"Yun-Ting Huang, C. McCarthy, M. Jani","doi":"10.3389/fdsfr.2023.1117674","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1117674","url":null,"abstract":"Pain management has been a challenging issue for people living with rheumatic and musculoskeletal diseases (RMDs) and health professionals for decades. Pharmacological treatments remain a core element of pain management of inflammatory arthritis and osteoarthritis. Yet balancing the benefits/harms in pain management within RMDs can be difficult to navigate due to limited effective options, and emerging adverse events in a population where individual risk is important to consider due to patient multimorbidity, immunosuppression and polypharmacy. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) analgesics are widely used among RMD patients, however both classes of drugs have been associated with new safety concerns in the last two decades. Perhaps as a result in combination with multifactorial influences, opioid prescribing has increased from the 2000s–2010s in the majority of RMD focussed studies, accompanied with a rising trend of long-term opioid use, despite limited evidence on efficacy. Gabapentinoids have also shown increasing trends more recently, despite an unclear role in chronic pain management for RMDs within current guidelines. Antidepressants are recommended as the first line of pharmacological treatment of chronic primary pain (e.g., fibromyalgia) by the latest National Institute for Health and Care Excellence (NICE) guideline released in April 2021. This concise narrative review will discuss pharmacological options for pain management, based on the latest evidence that includes the main analgesic drug classes: paracetamol, NSAIDs, opioids, antidepressants, and gabapentinoids. We will discuss the efficacy of these analgesics in RMDs and emerging safety concerns to enable more informed shared decisions with patients commencing such medications.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121103448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural language processing for automated triage and prioritization of individual case safety reports for case-by-case assessment","authors":"T. Lieber, H. Gosselt, Pelle C. Kools, Okko C. Kruijssen, Stijn N. C. Van Lierop, L. Härmark, F. van Hunsel","doi":"10.3389/fdsfr.2023.1120135","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1120135","url":null,"abstract":"Objective: To improve a previously developed prediction model that could assist in the triage of individual case safety reports using the addition of features designed from free text fields using natural language processing. Methods: Structured features and natural language processing (NLP) features were used to train a bagging classifier model. NLP features were extracted from free text fields. A bag-of-words model was applied. Stop words were deleted and words that were significantly differently distributed among the case and non-case reports were used for the training data. Besides NLP features from free-text fields, the data also consisted of a list of signal words deemed important by expert report assessors. Lastly, variables with multiple categories were transformed to numerical variables using the weight of evidence method. Results: the model, a bagging classifier of decision trees had an AUC of 0.921 (95% CI = 0.918–0.925). Generic drug name, info text length, ATC code, BMI and patient age. were most important features in classification. Conclusion: this predictive model using Natural Language Processing could be used to assist assessors in prioritizing which future ICSRs to assess first, based on the probability that it is a case which requires clinical review.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131604925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An industry perspective on the use of machine learning in drug and vaccine safety","authors":"Jeffery L. Painter, Raymond Kassekert, A. Bate","doi":"10.3389/fdsfr.2023.1110498","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1110498","url":null,"abstract":"In recent years there has been growing interest in the use of machine learning across the pharmacovigilance lifecycle to enhance safety monitoring of drugs and vaccines. Here we describe the scope of industry-based research into the use of machine learning for safety purposes. We conducted an examination of the findings from a previously published systematic review; 393 papers sourced from a literature search from 2000–2021 were analyzed and attributed to either industry, academia, or regulatory authorities. Overall, 33 papers verified to be industry contributions were then assigned to one of six categories representing the most frequent PV functions (data ingestion, disease-specific studies, literature review, real world data, signal detection, and social media). RWD and social media comprised 63% (21/33) of the papers, signal detection and data ingestion comprised 18% (6/33) of the papers, while disease-specific studies and literature reviews represented 12% (4/33) and 6% (2/33) of the papers, respectively. Herein we describe the trends and opportunities observed in industry application of machine learning in pharmacovigilance, along with discussing the potential barriers. We conclude that although progress to date has been uneven, industry is very interested in applying machine learning to the pharmacovigilance lifecycle, which it is hoped may ultimately enhance patient safety.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133353159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An open-source platform integrating emerging data sources to support multi-modal active pharmacovigilance","authors":"Vlasios K. Dimitriadis, Stella Dimitsaki, A. Chytas, G. Gavriilidis, C. Kakalou, Panos Bonotis, P. Natsiavas","doi":"10.3389/fdsfr.2022.1016042","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1016042","url":null,"abstract":"As new data sources have emerged, the data space which Pharmacovigilance (PV) processes can use has significantly expanded. However, still, the currently available tools do not widely exploit data sources beyond Spontaneous Report Systems built to collect Individual Case Safety Reports (ICSRs). This article presents an open-source platform enabling the integration of heterogeneous data sources to support the analysis of drug safety related information. Furthermore, the results of a comparative study as part of the project’s pilot phase are also presented. Data sources were integrated in the form of four “workspaces”: (a) Individual Case Safety Reports—obtained from OpenFDA, (b) Real-World Data (RWD) —using the OMOP-CDM data model, (c) social media data—collected via Twitter, and (d) scientific literature—retrieved from PubMed. Data intensive analytics are built for each workspace (e.g., disproportionality analysis metrics are used for OpenFDA data, descriptive statistics for OMOP-CDM data and twitter data streams etc.). Upon these workspaces, the end-user sets up “investigation scenarios” defined by Drug-Event Combinations (DEC). Specialized features like detailed reporting which could be used to support reports for regulatory purposes and also “quick views” are provided to facilitate use where detailed statistics might not be needed and a qualitative overview of the available information might be enough (e.g., clinical environment). The platform’s technical features are presented as Supplementary Material via a walkthrough of an example “investigation scenario”. The presented platform is evaluated via a comparative study against the EVDAS system, conducted by PV professionals. Results from the comparative study, show that there is indeed a need for relevant technical tools and the ability to draw recent data from heterogeneous data sources is appreciated. However, a reluctance by end-users is also outlined as they feel technical improvements and systematic training are required before the potential adoption of the presented software. As a whole, it is concluded that integrating such a platform in real-world setting is far from trivial, requiring significant effort on training and usability aspects.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114403491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events in rheumatoid arthritis patients under antimalarial treatment—Is there cardiovascular compromise?","authors":"P. Santos-Moreno, L. Ibatá, S. Martínez, G. Rodríguez-Vargas, L. Villarreal, P. Rodríguez, W. Rivero, F. Rodríguez-Florido, A. Rojas-Villarraga","doi":"10.3389/fdsfr.2022.1044696","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1044696","url":null,"abstract":"Introduction: The antimalarials chloroquine and hydroxychloroquine have been used for several decades in treating malaria and some autoimmune diseases—mainly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)—with excellent efficacy and safety. Due to the massive use of antimalarials worldwide for managing SARS-CoV-2/COVID-19 infection during the last 2 years and the consequent increase in cardiac arrhythmia, fear has risen about the safety of using antimalarials, especially for patients with increased cardiovascular risk. Objective: To describe a real-life experience about the safety of antimalarials in the setting of a single rheumatological center in Colombia. Methods: This is a cross sectional study that includes patients diagnosed with RA and treated with antimalarials between 2020 and 2021. Clinical follow-up information was gathered from the medical records, and all reported adverse events were described. Results: A total of 957 patients were included, primarily women (79.2%). The most frequent comorbidities were hypertension and osteoporosis. Chloroquine use was more frequent than hydroxychloroquine (86.4% vs. 13.6%). During the observation period, 243 (25.4%) patients presented at least one adverse event, 72 (29.6%) had retinal toxicity, 85 (35%) dermatological events, and 81 (33.3%) gastrointestinal intolerance. Other adverse events reported less frequently (15.2%) included headache, dizziness, lipothymia, and elevated transaminases. There were no reports of cardiovascular events from the period of antimalarial use to the date of data collection despite the high frequency of previous metabolic or cardiovascular disease in this cohort. Conclusion: This study reasserts the evidence of antimalarials safety profile for patients with rheumatological conditions such as RA. RA patients that were treated with antimalarials at doses recommended by the guidelines had no cardiovascular events.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114710550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deprescribing as a strategy for improving safety of medicines in older people: Clinical and regulatory perspective","authors":"S. Crisafulli, E. Poluzzi, C. Lunghi, V. Di Francesco, L. Pellizzari, L. Pasina, C. Elli, F. Trotta, A. Cangini, C. Trevisan, M. Zazzara, G. Onder, G. Trifirò","doi":"10.3389/fdsfr.2022.1011701","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1011701","url":null,"abstract":"The ageing process is associated with an increased probability of accumulating health deficits, chronic conditions and geriatric syndromes, leading to a growing prevalence of multimorbidity, defined as the co-occurrence of two or more chronic conditions (of which, at least one physical condition). One of the most frequent and direct consequences of multimorbidity, especially amongst older adults, is polypharmacy, a condition characterized by the concomitant use of five or more drugs per day. Polypharmacy is one of the main risk factors for adverse clinical outcomes, including drug-drug interactions and adverse drug reactions, also resulting in increased hospitalizations, morbidity, and increased use of healthcare resources, with considerable implications for healthcare costs. Deprescribing is one of potential approaches to reduce inappropriate prescribing and it is defined as the stopping or dose reduction of medications that are either inappropriate or unnecessary, especially among patients with polypharmacy. In this review, the major issues associated with polypharmacy among older people, the current guidelines for the management of polypharmacy and the strategies to implement deprescribing in different settings (i.e., hospital setting, nursing homes and general practice) are discussed.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115345501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicinal products, medical devices, or accessories of medical devices: How to qualify gases for spirometry?","authors":"Sara Manellari, M. Leone, A. Casiraghi, C. Gennari, P. Minghetti","doi":"10.3389/fdsfr.2022.1089965","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1089965","url":null,"abstract":"European legislation provides that each product used for healthcare purposes be regulated according to specific directives and regulations based on its intended use and mechanism of action. However, qualification issues may arise for medical devices, their accessories, and medicinal products. This is the case with gases for spirometry, which support spirometers in measuring patients’ pulmonary capacities. This article discusses criticisms connected to their proper regulatory qualification, detailing why they should be more properly qualified as accessories of medical devices instead of as medicinal products or medical devices.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125468710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new platform for post-marketing surveillance and real-world evidence data collection for substance-based medical devices","authors":"R. Cioeta, A. Cossu, E. Giovagnoni, M. Rigoni, P. Muti","doi":"10.3389/fdsfr.2022.992359","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.992359","url":null,"abstract":"The recent passage of European Union (EU) Regulation 2017/745 on medical devices (MDs) has improved the classification of MDs and revised their approval process and the post-marketing evaluation of their safety and effectiveness, promoting transparency and post-marketing oversight in Europe. This new regulation can better ensure patient safety and provide new opportunities for therapeutic innovation. In addition, the new regulations include and define MDs made of substances or of combinations of substances (substance-based MDs: SBMDs). The impressive growth of the MD, including SBMDs, that have been marketed over the recent years has likely been a relevant factor fueling this change. MD regulation requires a major effort from both industry and regulatory bodies to comply with its provisions. Manufacturers should produce sufficient clinical evidence that an MD, under normal conditions of use, provides adequate performance and that the foreseeable risks and frequency of adverse events (AEs) have an acceptable minimum rate, taking into account the benefits provided. We describe how we implemented the post-marketing surveillance (PMS) system of SBMDs to properly deal with post-market monitoring and confirmation of safety and performance, including AEs and the benefit–risk evaluation, as required by the 2017/745 Regulation. The two pillars of this novel system are: 1) passive vigilance, i.e., spontaneous reporting and 2) active post-marketing clinical follow-up (PMCF) activities, which systematically gather, record, and analyze real-world data (RWD) on performance, quality, function, use, tolerability, and safety of an MD, collected through a dedicated, structured web platform. Active PMCF is achieved through a process of generation, validation, and administration of digital questionnaires to all stakeholders, i.e., patients, physicians, both general practitioners and specialists, and pharmacists. The technology, potential use, advantages, and limitations of this large source of RWD are also discussed.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114401338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European Union Regulation on clinical trials and Regulation on medical devices: A common soil for future development","authors":"G. Rasi, A. Mugelli","doi":"10.3389/fdsfr.2022.1071620","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1071620","url":null,"abstract":"The recent European Union (EU) Regulations on clinical trial on medicinal products (MPs) (2014/536) and on medical devices (MD) (2017/745) represent potential improvement for the European health system and may offer advantages to the citizens. As Regulations, they are immediately applicable in Member States overruling national laws, being an advantage for stakeholders (e.g. sponsors and investigators) and Europe becomes de facto one homogeneous place for research and development of medicines and medical devices. This perspective commentary focuses on the most relevant methodological and regulatory aspects of the recent Regulation on clinical trials for drug development and how it may indirectly impact on substance-based medical devices (SBMD). The article highlights the innovations associated with the 2017/745 Regulation, especially to the area of SBMD, which represent a novelty among MDs. Since SBMDs share some aspects of medicines, they will increasingly undergo research in the future related to the performance and safety claims, via post-marketing surveillance. Importantly, SBMD’s Consumers are rapidly increasing due to their usage to treat some common symptoms, which not necessarily need conventional medicines. “Frontiers in Drug Safety and Regulation” created a section to reflect this rapidly-changing scenario and host reports on SBMD in a scientific environment. This initiative is also a reflection of the recent regulation on SBMDs. Thus, the improvement of clinical research through the new EU Regulation on clinical trials may become useful also to the new requirements for SBMD. A novel editorial initiative will further contribute to implement the EU Regulation providing adequate scientific dissemination.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127273041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a natural language processing tool for extracting gender, weight, ethnicity, and race in the US food and drug administration adverse event reporting system","authors":"V. Dang, E. Wu, C. Kortepeter, Michael Phan, Rongmei Zhang, Yong Ma, M. Muñoz","doi":"10.3389/fdsfr.2022.1020943","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1020943","url":null,"abstract":"The US Food and Drug Administration Adverse Event Reporting System (FAERS) contains over 24 million individual case safety reports (ICSRs). In this research project, we evaluated a natural language processing (NLP) tool’s ability to extract four demographic variables (gender, weight, ethnicity, race) from ICSR narratives. Specificity of the NLP algorithm was over 94% for all demographics, while sensitivity varied between the demographics: 98.6% (gender), 45.5% (weight), 100% (ethnicity), and 85.3% (race). Among ICSRs missing weight, ethnicity, and race in the structured field, few cases had this information in the narrative (>95% missing); consequently, the positive predictive value (PPV) for these three demographics had wide 95% confidence intervals. After NLP implementation, the total number of ICSRs missing gender was reduced by 33% (i.e., NLP identified 472 thousand reports having a gender value in the narrative that was not in the structured field), while the total number of ICSRs missing weight, ethnicity, or race was reduced by less than 4%. This study demonstrated that the implementation of an NLP tool can provide meaningful improvements in the availability of gender information for pharmacovigilance activities conducted with FAERS data. In contrast, NLP tools targeting the extraction of weight, ethnicity, or race from free-text fields have minimal impact largely because the information was infrequently provided by the reporter. Further gains in completeness of these fields must originate from increases in provision of demographic information from the reporter rather than informatic solutions.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116358193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}