Frontiers in Drug Safety and Regulation最新文献

{"title":"Medical Devices Made of Substances: The Need for a Change in Approach in Paediatrics","authors":"S. Stagi","doi":"10.3389/fdsfr.2022.867143","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.867143","url":null,"abstract":"Paediatricians are often called on to weigh up potential side effects and interferences associated with drug treatments. Ethical concerns often prevent clinical trials in children, meaning that specific data for the paediatric population can be lacking. This is true for pharmacological therapies and also natural remedies used as add-on therapy. Among natural health products are “medical devices made of substances” (MDMS) which have become increasingly important in the treatment of many disorders; the substances contained in MDMSs frequently consist of molecular structures present in a standardized preparation derived from a natural source which act as a “system.” The benefits of using MDMSs to treat paediatric conditions such as gastrointestinal disorders and obesity have been proven, although there remains a degree of uncertainty about the precise mechanism of action underlying their therapeutic effectiveness. This paper argues in favour of using MDSMs when there is scientific grounds to prove their efficacy.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"59 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125014651","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":"Pharmacological Versus Non-Pharmacological and Ancillary Mechanisms in Eye Drops Used in the Treatment of Glaucoma","authors":"N. Marchesi, F. Fahmideh, A. Barbieri, M. Racchi, A. Pascale, S. Govoni","doi":"10.3389/fdsfr.2022.933471","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.933471","url":null,"abstract":"Medical Devices Made of Substances (MDMS) are increasingly used in the healthcare system alongside classic medicinal products and constitute an important field of experimentation and innovation in the biomedical field. In fact, these products are rapidly establishing themselves as a valuable therapeutic resource and are available in various forms including, but not limited to, creams, syrups, nasal or oropharyngeal sprays, and eye drops. MDMS are marketed to treat different diseases and the advantages and benefits of the use of these products can be claimed, once proven their clinical activity. What are the differences between medicinal products and MDMS? The substantial difference lies in the mechanism of action: the first case is based on pharmacological, metabolic, and immunological actions while the second one is based on mechanical, or chemical/physical action. Sometimes the boundaries are not well defined and there is a need for a reassessment and a consensus on the underlying concepts and definitions, also in the light of the increasing ability to recognize molecular mechanisms underneath the action of several substances not acting through an easy recognizable unique target (as a receptor, for example). In the present paper, we discuss the role of eye drops as an example of MDMS used in glaucoma, a widely diffused eye disease. The choice is due to the fact that some products used in this field of application and containing similar substances are marketed either as medicinal products or as medical devices or, using other dosage forms, as food supplements. Accordingly, it is important to underscore in the various cases what may be the principal mode of action and the contribution of additional mechanisms as derived, for example, from system pharmacology data. Their analysis may help to exemplify some of the problems around the sometimes fuzzy border between MDMS and medicinal products suggesting the need for new definitions and regulatory decisions about MDMS.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129051876","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":"Increased Confidence in Deduplication of Drug Safety Reports with Natural Language Processing of Narratives at the US Food and Drug Administration","authors":"Kory Kreimeyer, Oanh Dang, Jonathan Spiker, Paula Gish, Jessica Weintraub, E. Wu, R. Ball, T. Botsis","doi":"10.3389/fdsfr.2022.918897","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.918897","url":null,"abstract":"The US Food and Drug Administration (FDA) receives millions of postmarket adverse event reports for drug and therapeutic biologic products every year. One of the most salient issues with these submissions is report duplication, where an adverse event experienced by one patient is reported multiple times to the FDA. Duplication has important negative implications for data analysis. We improved and optimized an existing deduplication algorithm that used both structured and free-text data, developed a web-based application to support data processing, and conducted a 6-month dedicated evaluation to assess the potential operationalization of the deduplication process in the FDA. Comparing algorithm predictions with reviewer determinations of duplicates for twenty-seven files for case series reviews (with a median size of 281 reports), the average pairwise recall and precision were equal to 0.71 (SD ± 0.32) and 0.67 (SD ± 0.34). Overall, reviewers felt confident about the algorithm and expressed their interest in using it. These findings support the operationalization of the deduplication process for case series review as a supplement to human review.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129551279","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":"Digital Therapeutics in Perspective: From Regulatory Challenges to Post-Marketing Surveillance","authors":"S. Crisafulli, E. Santoro, G. Recchia, G. Trifirò","doi":"10.3389/fdsfr.2022.900946","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.900946","url":null,"abstract":"Digital therapeutics (DTx) are innovative therapeutic interventions, in which the therapeutic activity is carried out by algorithms and software. They represent a new opportunity especially for the treatment of chronic pathologies associated with dysfunctional lifestyles and behaviors, where conventional drug therapy is not fully effective. DTx are highly customizable therapeutic tools, allowing a better involvement of the patient in the management of the disease. To date, the clinical use of DTx in Europe is still generally limited. One of the main issues related to DTx is the general lack of education of healthcare professionals in this sector that leads to a knowledge gap between data scientists, and physicians, who should identify all those clinical needs that could be better addressed through the use of DTx. From a regulatory perspective, DTx are classified as Medical Devices. However, their research and development process is similar to that of conventional drugs, since they are tested in clinical trials and their approval refers to specific therapeutic indications. For this reason, precise criteria for marketing approval, for the health technology assessment and for the reimbursement of these therapies need to be defined. Moreover, as for conventional drugs, it is also fundamental to conduct post-marketing studies on DTx, aiming at re-evaluating the benefit-risk profile and collecting information related to large-scale use in real world setting. The aim of this review is to describe the main challenges for DTx development, regulation and widespread clinical use.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"146 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123347438","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":"Efficacy and Safety of a Polysaccharide-Based Natural Substance Complex in the Treatment of Obesity and Other Metabolic Syndrome Components: A Systematic Review","authors":"G. Guarino, F. Strollo, P. Malfertheiner, T. Della Corte, S. Stagi, M. Masarone, S. Gentile","doi":"10.3389/fdsfr.2022.844256","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.844256","url":null,"abstract":"Introduction: Metabolic syndrome (MetS) is increasingly common in adults as well as in children and adolescents. However, preventing and treating MetS is one of the most pressing challenges for public health services worldwide. At present, the only approved treatments for MetS are dietary changes and physical activity, which are associated with a high rate of non-compliance. On the contrary, no drugs are licensed to treat metabolic syndrome, although a number of drugs are used to treat individual metabolic abnormalities, which increases the risk of adverse events, particularly in children. Policaptil Gel Retard® (PGR), an oral macromolecule complex based on polysaccharides, has been demonstrated to significantly reduce body weight, peak blood glucose (BG) levels, insulin levels, and lipid levels, providing an interesting non-pharmacological therapeutic option for MetS-associated metabolic abnormalities, especially in younger patients. Aims: To review available studies on the use of PGR in children, adolescents, or adults with obesity or metabolic syndrome. Methods: A systematic search of electronic databases for PGR and MetS. A total of six studies were identified and included. Results: Across four randomized clinical studies and one retrospective clinical study including a total of 359 obese children and adolescents with or without MetS and 157 overweight/obese adults with or without MetS and/or T2DM, a single dose of PGR resulted in a reduction in appetite and postprandial triglyceride levels in younger patients and peak postprandial BG levels in adults. Decreased lipid levels were observed in adults following a normocaloric diet who received PGR for 30 days. As a long-term treatment, in combination with a low-glycemic index diet with or without metformin, PGR resulted in reduced body mass index and waist circumference, improved insulin sensitivity with reduction of glucose-metabolism abnormalities, increased insulin reserve and, finally, an improved circulating lipid profile, regardless of age. No safety issues were reported. Conclusion: Policaptil Gel Retard® is an effective and safe non-pharmacological approach to improve the treatment of MetS-associated cardiovascular risk factors in children, adolescents, and adults.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124496658","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":"Current Status and Future Challenges in the Treatment of Rheumatic Diseases","authors":"E. Soriano","doi":"10.3389/fdsfr.2022.881556","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.881556","url":null,"abstract":"The strategic approach is probably as important as the incorporation of new drugs and their new mechanism of action. The strategic approach to rheumatic disease includes early diagnosis and early treatment, remission as the main objective of treatment, frequent assessment of disease activity using validated measurements tools, adjustment of treatment when the objective is not achieved (called treat to target strategy), and finally, shared therapeutic decisions with the patients. Each one of these strategic points are not only intuitively appealing, but also based on good evidence.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130034884","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 Era of Pharmacovigilance: Future Challenges and Opportunities","authors":"G. Trifirò, S. Crisafulli","doi":"10.3389/fdsfr.2022.866898","DOIUrl":"https://doi.org/10.3389/fdsfr.2022.866898","url":null,"abstract":"Medicines safety monitoring is a continuous and dynamic process throughout all the phases of the life cycle of a drug. During the drug development, safety is investigated in different phases. In preclinical studies, the primary goal of safety evaluation is the identification of a safe dose in humans and of safety parameters for clinical monitoring. In clinical phase, phase I studies are designed to estimate the tolerability of the dose range expected to be needed for later clinical studies in healthy volunteers; phase II studies are focused on determining appropriate range of drug doses in patients with a disease or condition of interest, while phase III clinical trials are the most important studies to refine understanding of benefit-risk profile of the drug and to identify less common adverse drug reactions. Although drug safety evaluation is very rigorous and thorough, pre-marketing clinical trials have however intrinsic limitations that do not allow to exhaustively evaluate drug safety profile (Singh and Loke, 2012). These studies are conducted on limited numbers of patients that are selected based on strict eligibility criteria and not fully representing real-world populations and have limited duration, thus preventing detection of rare and long-term adverse reactions. Therefore, the post-marketing assessment of medicines plays a key role for better defining drugs’ safety profile in real-world setting and filling the evidence gap of pre-marketing studies. In the field of drug safety and regulation, a number of challenges have to be faced in the near future. First of all, COVID-19 pandemic highlighted how relevant pharmacovigilance and proper risk communication during public health emergency are. Second, the development of advanced methodologies including machine learning techniques and the availability of large amount of electronic healthcare data offer opportunity for optimizing drug benefit-risk profile evaluation in real world setting. Finally, innovative therapeutics, such as advanced therapy medicinal products, digital therapeutics, vaccines developed based on advanced technologies, requiring special pharmacovigilance monitoring have been increasingly marketed in recent years, often upon accelerated pathway approval. Some of the challenges and future opportunities in this field are briefly discussed below.","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128718547","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":"Moving to a Personalized Approach in Respiratory Medicine. From Academic Research to Regulatory Intervention","authors":"M. Cazzola","doi":"10.3389/fdsfr.2021.752581","DOIUrl":"https://doi.org/10.3389/fdsfr.2021.752581","url":null,"abstract":"In recent years, interest in respiratory diseases has increased significantly after a long period of relative stagnation that followed the apparent control of tuberculosis. Indeed, for decades the focus of researchers was mainly on bronchial asthma, with little interest in COPD, and minimal attention on other lung diseases. Despite the widespread prevalence of pulmonary diseases, there has been, and still is, a considerable delay in understanding their etiopathogenesis, and, as a result, the therapeutic approach to these diseases has not developed adequately. For as long as anyone can remember, it has generally been limited to the use of bronchodilators, corticosteroids, mucolytics and antibiotics. Recent advances in biomedical research and bioinformatics approaches, in particular the commodification of high-throughput biotechnology, are now enabling the understanding of various aspects of biological systems. Insights generated by these advances have gone beyond the limitations of simplistic hypotheses. The obvious consequence of this is that the fundamental mechanisms that regulate biological processes in the lungs are increasingly being discovered, and, as a cascade, several disease endotypes and new therapies that may be effective in selected individuals are also being identified (Hemnes, 2018). Nonetheless, these approaches still have serious limitations due to a high chance of potentially false discovery with low patient numbers, inexact phenotyping, and bioinformatics challenges. However, the broadening of our knowledge of the underlying mechanisms involved in at least some phenotypes and endotypes of asthma and/or COPD has provided access to innovative therapies, especially for asthma (Cazzola et al., 2017; Martin et al., 2019; Rogliani et al., 2020; Cazzola et al., 2021; Matera et al., 2021). Unfortunately, however, it is becoming increasingly accepted that asthma and COPD are chronic inflammatory airway disorders that are highly heterogeneous in terms of pathogenic manifestations, symptom severity and outcome (Sterk, 2016). There is growing evidence that asthma and COPD are umbrella terms used to group endotypes characterised by different underlying mechanisms (Rogliani et al., 2016). These endotypes probably represent diseases that are different and therefore each characterised by clinical and pathological heterogeneity, although there may also be overlapping features (Rogliani et al., 2016). Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease (ILD) with a poor prognosis, which has received much attention in recent years, is also difficult to classify because it is extremely heterogeneous in terms of clinical progression rates, worsening in lung function decline, and treatment response (Clarke et al., 2017). IPF represents the archetype of progressive fibrosing ILD, but many patients with other ILD subtypes also develop progressive fibrosing ILD (Bowman et al., 2021). Furthermore, the variability in clinical progres","PeriodicalId":321587,"journal":{"name":"Frontiers in Drug Safety and Regulation","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127283457","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}