Frontiers in drug safety and regulation最新文献

{"title":"Application of the target trial emulation framework to external comparator studies","authors":"Kellyn Arnold, Luis Antunes, Briana Coles, Hopin Lee","doi":"10.3389/fdsfr.2024.1380568","DOIUrl":"https://doi.org/10.3389/fdsfr.2024.1380568","url":null,"abstract":"External comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, the reliability of evidence generated from EC studies can vary. In this paper, we outline how an existing framework for causal inference, the target trial emulation (TTE) framework, can be appropriately applied to improve the design and analysis of EC studies. Applying the TTE framework involves specifying the protocol of an ideal target trial which would answer the causal question of interest, then emulating its key elements under real-world (RW) settings. We describe each component of the original TTE framework and explain how it can be applied to EC studies, supplemented with practical recommendations. We also highlight special considerations and limitations in applying the TTE framework to EC studies. We describe how the TTE framework can be applied to improve the clarity, transparency, and reliability of evidence generated from EC studies.","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"22 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714748","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":"Regulation 2017/745 on medical devices, two major innovations: 1) the physiological action of devices consisting of natural materials such as vegetal matrices; 2) the chemical-physical-mechanical action of devices made of “substances”, which as such are artificial derivatives","authors":"Marcella Marletta","doi":"10.3389/fdsfr.2024.1389406","DOIUrl":"https://doi.org/10.3389/fdsfr.2024.1389406","url":null,"abstract":"The Medical Device Regulation 2017/745 (MDR) enables the development of a wide range of innovative products. With respect to Directive 93/42, the MDR explicitly identifies the so-called “medical devices made of substances” (MDMS) through specific requirements. In addition, the MDR expands the definition of medical device (MD) by including the “modification of a physiological or pathological state” as a medical purpose specific to devices. This clarifies that materials interacting with the human body in such a way as to modify its “state” are medical devices. Natural materials, such as vegetal matrices, are characterized by the presence of both functional and structural interactions between their components; they can thus be described as “network/s\" and interact with the human body in a coordinated, complex way. Since the “state” of the human body is a network of biological functions, the “network/s over a network” interaction between the natural material and the human body is likely to modify the “state” of the human body. Thus, therapeutic products consisting of natural materials, such as vegetal matrices, seem to fit perfectly into the definition of a medical device. Here we analyze the main characteristics of medicinal products, of medical devices made of substances and of medical devices consisting of natural materials. We see that medicinal products and medical devices made of substances have the common characteristic of being based on substances, either synthetic or derivatives of natural materials, but differ in their mechanism of action. On the other hand, medical devices constituted of natural materials relate to the general category of medical devices and cannot be characterized by any single component, identified as an active component. We also discuss how these characteristics relate to the mechanism of action of each type of product. This analysis should allow to identify the most appropriate path for each product, a necessary step to promote research and development of innovative therapies for a large number of unmet medical needs.","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140750442","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":"Editorial: Traditional and innovative approaches for signal detection","authors":"Marco Tuccori, Andrew Bate, Ugo Moretti, Gianluca Trifirò","doi":"10.3389/fdsfr.2024.1373689","DOIUrl":"https://doi.org/10.3389/fdsfr.2024.1373689","url":null,"abstract":"","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139799195","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":"Editorial: Traditional and innovative approaches for signal detection","authors":"Marco Tuccori, Andrew Bate, Ugo Moretti, Gianluca Trifirò","doi":"10.3389/fdsfr.2024.1373689","DOIUrl":"https://doi.org/10.3389/fdsfr.2024.1373689","url":null,"abstract":"","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"115 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139858807","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":"Editorial: Treatment of comorbidities of asthma and its safety","authors":"Serghei Covantsev, Alexandru Corlateanu","doi":"10.3389/fdsfr.2024.1366847","DOIUrl":"https://doi.org/10.3389/fdsfr.2024.1366847","url":null,"abstract":"","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"23 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139805507","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":"Editorial: Treatment of comorbidities of asthma and its safety","authors":"Serghei Covantsev, Alexandru Corlateanu","doi":"10.3389/fdsfr.2024.1366847","DOIUrl":"https://doi.org/10.3389/fdsfr.2024.1366847","url":null,"abstract":"","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139865577","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":"External comparators and estimands","authors":"Gerd Rippin","doi":"10.3389/fdsfr.2023.1332040","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1332040","url":null,"abstract":"The estimand framework as defined by the ICH E9(R1) addendum aims to clearly define “the treatment effect reflecting the clinical question posed by the trial objective”. It intends to achieve this goal of a clear definition by specifying the 5 estimand attributes: treatment conditions, population, endpoints, handling of intercurrent events (IEs), and population-level summary. However, hybrid clinical/observational research like External Comparators (ECs) leads to new reflections on existing attributes and to considerations for additional ones. Specifically, treatment conditions and exposure may be more difficult to handle in the EC, and especially Standard of Care (SoC) treatment needs detailed attention. The external population typically cannot be based on the classical Intention-to-treat population and constitutes also an approximation only. Endpoints may not be comparable across cohorts, and IEs may be more different than in an RCT setting, such that the hypothetical treatment policy according to the ICH E9(R1) addendum may become of greater interest especially for long-term endpoints. Finally, the necessary assumptions for some population-level summaries (e.g., the proportional hazards assumption) can become more fragile when joining data from different sources due to induced heterogeneity. Finally, it is shown that the baseline definition and the marginal estimator are candidates for additional estimand attributes in case the estimand framework is revised to account for observational study needs.","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"47 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139809861","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":"External comparators and estimands","authors":"Gerd Rippin","doi":"10.3389/fdsfr.2023.1332040","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1332040","url":null,"abstract":"The estimand framework as defined by the ICH E9(R1) addendum aims to clearly define “the treatment effect reflecting the clinical question posed by the trial objective”. It intends to achieve this goal of a clear definition by specifying the 5 estimand attributes: treatment conditions, population, endpoints, handling of intercurrent events (IEs), and population-level summary. However, hybrid clinical/observational research like External Comparators (ECs) leads to new reflections on existing attributes and to considerations for additional ones. Specifically, treatment conditions and exposure may be more difficult to handle in the EC, and especially Standard of Care (SoC) treatment needs detailed attention. The external population typically cannot be based on the classical Intention-to-treat population and constitutes also an approximation only. Endpoints may not be comparable across cohorts, and IEs may be more different than in an RCT setting, such that the hypothetical treatment policy according to the ICH E9(R1) addendum may become of greater interest especially for long-term endpoints. Finally, the necessary assumptions for some population-level summaries (e.g., the proportional hazards assumption) can become more fragile when joining data from different sources due to induced heterogeneity. Finally, it is shown that the baseline definition and the marginal estimator are candidates for additional estimand attributes in case the estimand framework is revised to account for observational study needs.","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"8 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139869845","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":"Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems","authors":"P. Cutroneo, Daniele Sartori, Marco Tuccori, Salvatore Crisafulli, V. Battini, Carla Carnovale, C. Rafaniello, Annalisa Capuano, E. Poluzzi, Ugo Moretti, E. Raschi","doi":"10.3389/fdsfr.2023.1323057","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1323057","url":null,"abstract":"Spontaneous reporting systems remain pivotal for post-marketing surveillance and disproportionality analysis (DA) represents a recognized approach for early signal detection. Although DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient, their role remain irreplaceable for rapid detection of rare and unpredictable adverse drug reactions with strong drug-attributable component (e.g., designated medical events), especially when developed by a multidisciplinary team and combined with a careful case-by-case analysis (individual inspection of reports for causality assessment or to uncover reporting patterns and clinical features). In the recent past, a remarkable increase in publications of pharmacovigilance studies using DAs was observed, albeit the quality was debated: several publications contained “spin”, namely, misinterpretation of results to infer causality, calculate incidence, or provide risk stratification, which may ultimately result in unjustified alarm. The development of dedicated Guidelines by the international READUS-PV project (https://readus-statement.org/) will allow reproducible and transparent publication of accurate DAs, thus supporting their real transferability and exploitation by regulators and clinicians. This review offered a perspective on methodological aspects (and understanding) of DAs, their rationale, design, reporting, and interpretation.","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"53 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594766","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":"External Comparator Cohort studies clarification of terminology","authors":"Gerd Rippin, Joan Largent, Wilhelmina Elisabeth Hoogendoorn, Héctor Sanz, Jaclyn Bosco, Christina Mack","doi":"10.3389/fdsfr.2023.1321894","DOIUrl":"https://doi.org/10.3389/fdsfr.2023.1321894","url":null,"abstract":"Though there is only one term for the gold standard of Randomized Controlled Trials the terminology used for controlled research involving external data is diverse. Common terms include External Comparator/Control Arm study, Externally Controlled Trial, Synthetic Control study and Historical Control study. The term Externally Controlled Trial was recently selected by the U.S. Food and Drug Administration (FDA) and is in line with the use case of a pivotal trial. It entails pre-specification of the external dataset and its analysis in the trial protocol, which produces the highest amount of transparency, which is an important aspect for maximum credibility. If this pre-specification did not occur, we advocate the term External Comparator Cohort study (or short External Comparator study), which is derived by scrutinizing the paired terms study/trial, control/comparator and arm/cohort. Furthermore, we propose an overall framework of nomenclature, which is generally applicable for research projects involving external data. Only a precise and consistent use of terminology will most effectively safeguard from unintended implications, inaccurate perceptions, and misguided mindsets.","PeriodicalId":489826,"journal":{"name":"Frontiers in drug safety and regulation","volume":"5 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139600492","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}