Frontiers in Drug Safety and Regulation最新文献

{"title":"Exploring opportunities for AI supported medication error categorization: A brief report in human machine collaboration","authors":"Allan Fong, C. Bonk, V. Vasilchenko, S. De, Douglas Kovich, Jo Wyeth","doi":"10.3389/fdsfr.2022.1021068","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1021068","url":null,"abstract":"Understanding and mitigating medication errors is critical for ensuring patient safety and improving patient care. Correctly identifying medication errors in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports can be difficult because of the complexities of medication error concepts. We took a user-centered design approach to support the medication error categorization workflow process with artificial intelligence (AI). We developed machine learning models to categorize medication error terms. The average F1-score, precision, recall, and area under the precision recall curve for 18 Medical Dictionary for Regulatory Activities (MedDRA) Lower Level Term (LLT) relating to medication errors were 0.88, 0.92. 0.85, and 0.83 respectively. We developed a framework to help evaluate opportunities for artificial intelligence integration in the medication error categorization workflow. The framework has four attributes: technical deployment, process rigidity, AI assistance, and frequency. We used the framework to compare two AI integration opportunities and concluded that the quality assurance (QA) opportunity to be a more feasible initial option for AI integration. We then extended these insights into the development and user testing of a prototype application. The user testing identified the highlighting and commenting capabilities of the application to be more useful and sliders and similar report suggestions to be less useful. This suggested that different AI interactions with human highlighting should be explored. While the medication error quality assurance prototype application was developed for supporting the review of direct FAERS reports, this approach can be extended to assist in the workflow for all FAERS reports.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128470620","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":"Corrigendum: Substance-based medical devices made of natural substances: An opportunity for therapeutic innovation","authors":"E. Giovagnoni","doi":"10.3389/fdsfr.2022.1054972","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1054972","url":null,"abstract":"","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"19 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113989337","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":"Establishing patient safety monitoring in the benefit-risk paradigm for off-label and emergency use of medications for COVID-19: A pharmacovigilance perspective","authors":"M. Malikova, G. Trifirò, G. Racagni, Dennis J. Van Liew, Peggy Webster, Tejal S. Brahmbhatt","doi":"10.3389/fdsfr.2022.1038235","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1038235","url":null,"abstract":"Department of Surgery, School of Medicine, Boston University, Boston, MA, United States, Boston Medical Center, Boston, MA, United States, Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Department of Pharmacological and Biomolecular Sciences, Faculty of Pharmacy, University of Milan, Milan, Italy, Red Nucleus, Waltham, MA, United States, Glaxo SmithKline, Cambridge, MA, United States","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130818912","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":"Riluzole use in presence of contraindications in adults affected by amyotrophic lateral sclerosis and its off-label use in other motor neuron diseases: Findings from an Italian multicentre study (the CAESAR project)","authors":"G. Crescioli, Marco Finocchietti, S. Cascini, O. Paoletti, D. Franchini, E. Cappello, G. Valdiserra, F. Sciancalepore, M. Celani, M. Tuccori, A. Vannacci, N. Lombardi, U. Kirchmayer","doi":"10.3389/fdsfr.2022.1041275","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1041275","url":null,"abstract":"Background: This analysis describes the use of riluzole in amyotrophic lateral sclerosis (ALS) individuals with contraindications and off-label use for subjects with other motor neuron diseases (o-MND) in the Italian regions of Latium, Tuscany and Umbria. Methods: A cohort of adults with ALS prescribed with riluzole during the years 2016–2019 was enrolled from administrative healthcare databases, excluding subjects with o-MND in the preceding 5 years. Being affected by ALS for more than 5 years, presence of tracheostomy, renal or hepatic failure were considered as contraindications to the use of riluzole. A cohort of adults with o-MND was enrolled in 2016–2019 for whom off-label use of riluzole was retrieved up to 4 years, analysing over the time differences related to sex. Results: Among 206 ALS individuals prescribed with riluzole in Latium, 336 in Tuscany and 60 in Umbria, less than 1% were diagnosed with ALS for more than 5 years. Less than 2% were tracheotomised or affected by hepatic failure. Renal failure was documented for 1.9%, 2.7%, and 5.0% of ALS individuals in Latium, Tuscany and Umbria. The o-MND cohort comprised 264 subjects in Latium, 222 in Tuscany, and 66 in Umbria. Non-negligible off-label riluzole use was observed: 8.5%, 33.0%, and 4.2% in females, and 19.9%, 26.5% and 2.4% in males in Latium, Tuscany and Umbria. Discussion: Riluzole use in ALS individuals in the presence of contraindications is rare, with slightly higher numbers in presence of renal failure. Off-label use in o-MND was found to be non-negligible, with variations between sexes.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130002526","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":"Putting external validation performance of major bleeding risk models into context","authors":"C. Blacketer, J. Reps, Lu Wang, P. Ryan, Zhong Yuan","doi":"10.3389/fdsfr.2022.1034677","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1034677","url":null,"abstract":"When developing predictive models, model simplicity and performance often need to be balanced. We propose a novel methodology to put the performance of bleeding risk prediction models ORBIT, ATRIA, HAS-BLED, CHADS2, and CHA2DS2-VASc into perspective. Instead of comparing the existing models’ performance against the 0.5–1 AUROC scale, we suggest estimating a prediction task specific AUROC scale, lower bound AUROC (lbAUROC) and upper bound AUROC (ubAUROC), to help assess the balance between model simplicity and performance and determine whether more complex models could significantly improve the ability to predict the outcome. We validate the existing bleeding risk prediction models by applying them to a cohort of new users of warfarin and a cohort of new users of direct oral anticoagulants (DOACs) separately, across a set of four observational databases. Then, we develop the lbAUROC-ubAUROC scale by using the validation data to train regularized logistic regression models. The internal validation AUROC of the model that includes only age and gender variables was used to estimate the lbAUROC. The internal validation AUROC of the model that includes thousands of candidate variables was used to estimate the ubAUROC. The age and gender only models achieved AUROCs between 0.50 and 0.56 (lower bound) and the large-scale models achieved AUROCs between 0.67 and 0.72 and between 0.70 and 0.77 (upper bound) within the target cohorts of warfarin new users and DOACs new users, respectively. The AUROC of existing bleeding risk prediction models fall between the upper-bound and lower-bound of predictive models. Our study showed that this context of the predictability of the outcome is essential when evaluating risk prediction models to be administered in actual practice.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125454398","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":"Effectiveness and tolerability of Poliprotect, a natural mucosal protective agent for gastroesophageal reflux disease and dyspepsia: Surveys from patients, physicians, and pharmacists","authors":"R. Cioeta, P. Muti, M. Rigoni, L. Morlando, Filippo Siragusa, A. Cossu, E. Giovagnoni","doi":"10.3389/fdsfr.2022.969831","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.969831","url":null,"abstract":"Background: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are very common in the general population. GERD prevalence is considerably high in pregnant women, and it increases at a young age, alongside obesity. Mucosal protective agents (MPAs) are over-the-counter (OTC) treatments for FD and GERD commonly used alone or as add-on therapy to proton pump inhibitors (PPIs). Real-world data through surveys allow a clinical evaluation of marketed products that also complies with the new regulation on substance-based medical devices (SBMDs). Aim: The study aimed to evaluate perceived effectiveness, safety, and pattern of usage among patients, physicians, and pharmacists of the natural MPA Poliprotect, as assessed by a validated survey methodology. Methods: Questionnaire repeatability was first assessed, resulting in the intraclass correlation coefficient agreement level >0.9 in the three validation cohorts of physicians, pharmacists, and patients. All questions were closed multiple-choice, allowing measuring variations in frequency, quality, or magnitude of effect on a 5-point Likert-like verbal scale. Results: Three different surveys were performed in Italy and Spain on a total of 3,471 physicians, including 77 gastroenterologists, 848 patients, and 146 pharmacists who had an experience with Poliprotect in the previous year. Over 90% of general practitioners (GPs) rated Poliprotect effectiveness as good/excellent in controlling pyrosis, 80% for epigastric pain, and approximately 70% for digestion difficulties. GPs reported Poliprotect as very or extremely useful as an alternative to PPIs (73%) and for pregnancy-associated GERD symptoms (61%), almost unanimously (99.5%) reporting an excellent to good tolerability; 79% of the gastroenterologists answered to be extremely or very satisfied with the improvement of typical GERD symptoms, whereas improvement of dyspepsia and pregnancy- and breast-feeding-associated GERD symptoms was rated as highly satisfactory for 69, 52, and 62%, respectively, among GI specialists. Its use because of painful dyspeptic symptoms was reported by over 80% of patients, who rated symptom relief as excellent/good, and reported a marked quality-of-life improvement in 73% and in 65% of their answers, respectively. The product was used as monotherapy by 63% of patients. Conclusion: Large-scale, validated surveys support the safety and effectiveness of Poliprotect in the treatment of common functional upper GI disorders.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133250517","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":"New regulation on medical devices made of substances: Opportunities and challenges for pharmacological and toxicological research","authors":"C. Fimognari, E. Barrajón-Catalán, C. Luceri, E. Turrini, E. Raschi, E. Bigagli","doi":"10.3389/fdsfr.2022.1001614","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.1001614","url":null,"abstract":"The Medical Device (MD) Regulation EU 2017/745 (MDR) has provided a completely new and more robust regulatory framework at guarantee of the safety and efficacy of therapeutic options accessing the market. At the same time, the MDR poses several challenges for stakeholders, among which, the most significant lying on MDs made of substances (MDMS) whose mechanism of action should be non-pharmacological, immunological, or metabolic. Moving from single active substances to very complex mixtures, such as the case of natural products, the demonstration of the non-targeted, non-pharmacological mechanism, is even much more challenging since it is very hard to specifically identify and characterize all the interactions each constituent can have within the body. New scientific paradigms to investigate these multiple interactions and delineate the principal mechanism of action through which the effect is achieved are necessary for the correct regulatory classification and placement in the market of MDMS. This article will discuss the difficulties in delineating the boundaries between pharmacological and non-pharmacological mechanisms, practical approaches to the study of complex mixtures and the challenges on the application of current experimental paradigms to the study of the mechanism of action of MDMS.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125741767","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":"Substance-based medical devices made of natural substances: An opportunity for therapeutic innovation","authors":"E. Giovagnoni","doi":"10.3389/fdsfr.2022.998114","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.998114","url":null,"abstract":"The approval of EU Regulation 2017/745 has created a regulatory framework capable of consolidating an entire category of therapeutic products, that of Substance-based Medical Devices. The Regulation creates the conditions required to promote innovation in therapeutics, both for the so-called “minor illnesses” as well as for important “unmet medical needs”. At the same time, it significantly raises the standards for evaluating their efficacy and safety. Among the different kinds of Substance-based Medical Devices, those made of natural complex substances offer a special opportunity. In this new regulatory context, natural substances can be made available to the patient within an “evidence-based” context, guided by the principles of Systems Biology and Systems Medicine, and under the control of the healthcare sector. Substance-based Medical Devices are already an important product in the European therapeutic market and will likely play an increasing role in the years to come.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"124 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116893772","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":"Towards a European harmonization of health technology assessment recommendations executive paper of European regulatory conference focused on the EU commission proposal to harmonize HTA","authors":"L. Gozzo, K. Paterson, O. Wong, F. Megerlin, J. Geldmacher, P. Popoli, C. Jommi, F. Fricke, Oriol de Solà-Morales, I. Kamae, G. Rasi, F. Drago","doi":"10.3389/fdsfr.2022.970661","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.970661","url":null,"abstract":"Health Technology Assessment (HTA) is a multidisciplinary process which supports policy “decision-making”, including those related to drug reimbursement and price negotiation based on comprehensive clinical and non-clinical evaluations. The discrepancies in HTA recommendations among European countries are related to the differences in health care systems and willingness to invest in health care, differences in assessment methodologies and appraisal practices, and variations in economic constraints, and may produce disparities in terms of patient access to medicines. The political discussion about the adoption of the European Regulation on HTA lasted for years due to concerns about its feasibility and its implications for national health care systems In this paper we highlighted the importance to harmonize HTA process in Europe and some critical issues emerged during the discussion among experts in the field carried out at the European Regulatory Conference.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117209242","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":"Medical Devices Made of Substances: A New Challenge","authors":"M. Leone","doi":"10.3389/fdsfr.2022.952013","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.952013","url":null,"abstract":"Regulation (EU) 2017/745 provides for new provisions for medical devices made of substances as well as specific classification rules and requirements. The demarcation line between medical devices composed of substances and medicinal products is not always easy to define. The recent publication by the European Commission of the guidance on borderline between medical devices and medicinal products under the Regulation (EU) 2017/745 on medical devices, MDCG 2022-5, addresses some important issues in this topic. This article will discuss some controversial aspects in this field in order to clarify the product qualification process.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117129416","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}