Therapeutic innovation & regulatory science最新文献_第2页

A Sponsor's Best Practice and Operating Principles to Manage Data Monitoring Committees. 赞助商管理数据监控委员会的最佳实践和操作原则。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2025-01-07 DOI: 10.1007/s43441-025-00742-w

Malene Muusfeldt Birck, Josephine Skovgaard Rasmussen, Ida Carøe Helmark, Karsten Lollike

{"title":"A Sponsor's Best Practice and Operating Principles to Manage Data Monitoring Committees.","authors":"Malene Muusfeldt Birck, Josephine Skovgaard Rasmussen, Ida Carøe Helmark, Karsten Lollike","doi":"10.1007/s43441-025-00742-w","DOIUrl":"10.1007/s43441-025-00742-w","url":null,"abstract":"The use of data monitoring committees (DMC) to safeguard patients' safety in clinical trials has evolved over the last decades and has become increasingly common. To ensure well-operating and high-performing DMCs, pharmaceutical companies need to establish clearly defined operational processes while continuously seeking to optimize these and adapt to the needs of drug development. Although there are health authority guidelines on establishing and managing a DMC, the perspectives and experiences of sponsors are often underrepresented. This publication shares insights on a sponsor, Novo Nordisk (NN), regarding principles and practices for DMC establishment and management across varying trial types and therapeutic areas, including challenges and solutions. Highlighting NN's structured and successful approach to DMCs, it details clearly defined roles and responsibilities that ensure productive DMC meetings and high-quality data for the DMC. Additionally, NN's practices for clear, transparent, and trustful communication between the sponsor, the DMC, and the independent external statistical vendor are described. Processes for quality control, internal audits, and learnings from inspections and how these are incorporated for continuous improvement of the DMC process are discussed. While the processes and practices described are primarily designed for medium and large pharmaceutical companies, certain aspects may also be relevant and beneficial for smaller companies.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"215-221"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inside the Mind of the DMC: A Review of Principles and Issues with Case Studies. DMC的思想内部：用案例研究回顾原则和问题。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2024-12-17 DOI: 10.1007/s43441-024-00720-8

Lizhao Ge, Toshimitsu Hamasaki, Scott R Evans

{"title":"Inside the Mind of the DMC: A Review of Principles and Issues with Case Studies.","authors":"Lizhao Ge, Toshimitsu Hamasaki, Scott R Evans","doi":"10.1007/s43441-024-00720-8","DOIUrl":"10.1007/s43441-024-00720-8","url":null,"abstract":"A data monitoring committee (DMC) can have an extremely challenging job. Stop a trial too soon, and results are inconclusive and the trial fails to obtain answers to important questions that could inform future clinical practice. Stop a trial too late, and trial participants are exposed to potentially harmful or ineffective interventions longer than necessary. Securing convincing and conclusive evidence and the ethical responsibility to current and future patients are weighed carefully during DMC deliberations. The ability to interpret complex information, and appreciation of issues affecting scientific integrity, are critical for the DMC to protect trial participants and public trust. Challenges faced by and issues of prudence faced by DMCs are discussed including interim analysis issues, assessing the totality of information with statistical boundaries as guidelines, interpretation of composite and surrogate outcomes, reactions to early trends, benefit:risk assessment, landscape changes, subgroup analyses, composing information for a comprehensive understanding of patient-centric effects, and evaluating the value of additional data. Case studies illustrate how DMCs addressed the challenges.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"234-244"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of the Regulatory Review Process of the Zambia Medicines Regulatory Authority: Challenges and Opportunities. 赞比亚药品监管局监管审查程序的评估：挑战和机遇。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2024-12-27 DOI: 10.1007/s43441-024-00730-6

Constance Sakala Chisha, Makomani Siyanga, Stephanie Leigh, Adem Kermad, Stuart Walker

{"title":"Evaluation of the Regulatory Review Process of the Zambia Medicines Regulatory Authority: Challenges and Opportunities.","authors":"Constance Sakala Chisha, Makomani Siyanga, Stephanie Leigh, Adem Kermad, Stuart Walker","doi":"10.1007/s43441-024-00730-6","DOIUrl":"10.1007/s43441-024-00730-6","url":null,"abstract":"Purpose: This study aimed to assess the current regulatory review process of the Zambia Medicines Regulatory Authority (ZAMRA) by identifying the key milestones and target timelines achieved for products approved from 2020 to 2023, as well as good review and quality decision-making practices implemented in the review process.Methods: A standardised, validated questionnaire; Optimising Efficiencies in Regulatory Agencies (OpERA) and the OpERA Data Collection Template were completed by the author.Results: Three review models are used by ZAMRA to review new active substances (NASs) and generic products: verification, for products prequalified by the World Health Organization or approved by a stringent regulatory authority (SRA); abridged, for well-established molecules or SRA-approved products; or full, for products not otherwise prequalified. Good review practices and quality decision-making processes were followed but could be improved.Conclusion: This study assessed the overall ZAMRA operation and identified the key milestones in the review process for products approved from 2020 to 2023, target timelines achieved and the compliance to standard good review and quality decision-making practices.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"304-318"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a Drug Safety Signal Detection Reference Set Using Japanese Safety Information. 基于日本安全信息的药品安全信号检测参考集的研制。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2024-12-21 DOI: 10.1007/s43441-024-00729-z

Satoru Ito, Mamoru Narukawa

{"title":"Development of a Drug Safety Signal Detection Reference Set Using Japanese Safety Information.","authors":"Satoru Ito, Mamoru Narukawa","doi":"10.1007/s43441-024-00729-z","DOIUrl":"10.1007/s43441-024-00729-z","url":null,"abstract":"Introduction: One of the main objectives of pharmacovigilance activities is to confirm unknown adverse drug reactions (ADRs), and data-mining methods have been developed to detect signals that are candidates for ADRs. Reference sets have been developed to evaluate the performance of the data-mining methods. However, reference sets generated in previous studies are not based on Japanese safety information; therefore, they are not suitable for use in evaluation studies in Japan because some drugs have not been approved or marketed for a long time in Japan. This study aimed to develop a reference set using drug safety information marketed in Japan and to evaluate its performance.Methods: A reference set was developed for 43 drugs and 15 events. For each combination of the selected drug and event, those that were listed as important identified risks in the Japan Risk Management Plan (J-RMP) were set as \"positive controls\" and those that were not listed as adverse reactions in the package insert were set as \"negative controls.\" In addition, we performed data-mining using Japanese Adverse Drug Event Report database (JADER) and evaluated the results against the reference set to empirically confirm its effectiveness.Results: The reference set included 127 positive and 386 negative controls. A comparison of the signals obtained from data-mining using JADER with the reference set revealed higher correlations than those in previous studies.Conclusion: A reference set was developed using the safety information of drugs approved in Japan to promote research on data-mining methods.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"288-294"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mixture Disease Progression Model to Predict and Cluster the Long-Term Trajectory of Cognitive Decline in Alzheimer's Disease. 混合疾病进展模型预测和聚类阿尔茨海默病认知能力下降的长期轨迹。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2024-12-13 DOI: 10.1007/s43441-024-00708-4

Ryoichi Hanazawa, Hiroyuki Sato, Akihiro Hirakawa

{"title":"Mixture Disease Progression Model to Predict and Cluster the Long-Term Trajectory of Cognitive Decline in Alzheimer's Disease.","authors":"Ryoichi Hanazawa, Hiroyuki Sato, Akihiro Hirakawa","doi":"10.1007/s43441-024-00708-4","DOIUrl":"10.1007/s43441-024-00708-4","url":null,"abstract":"Background: Alzheimer's disease (AD) is a neurodegenerative disease for which many clinical trials failed to detect treatment effects, possibly due to the heterogeneity of disease progression among the patients. Predicting and clustering a long-term trajectory of cognitive decline from the short-term cognition data of individual patients would help develop therapeutic interventions for AD.Methods: This study developed mixture disease progression model to predict and cluster the long-term trajectory of cognitive decline in the population. We predicted the 30-year long-term trajectories of the three cognitive scales and categorized the individuals into rapid and slow cognitive decliners by applying the method, which was based on the two-component normal mixture nonlinear mixed-effects model, to the short-term follow-up data of the Mini-Mental State Examination, the 13-item Alzheimer's Disease Assessment Scale-Cognitive, and the Clinical Dementia Rating Scale-sum of boxes collected in patients with mild cognitive impairment and AD in the Alzheimer's Disease Neuroimaging Initiative.Results: For each cognitive scale, the models identified two distinct subpopulations, including a population of comprising approximately 10-20% of individuals experiencing rapid cognitive decline, wherein the posterior means of the differences in cognitive decline speed between the two groups ranged from 2 to 3 years. We also identified baseline background factors associated with rapid decliners for three cognitive scales.Conclusion: Identifying the risk factors associated with rapid decline of cognition by the proposed method aids in planning eligibility criteria and allocation strategy for accounting for the varying disease progression speeds among the patients enrolled in clinical trials for AD.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"264-277"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond Juul: The New Face of Underage Nicotine Addiction - A Survey of College Students. 超越Juul：未成年人尼古丁成瘾的新面孔——一项对大学生的调查。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2024-12-28 DOI: 10.1007/s43441-024-00735-1

Griffin Riggs, Terry David Church

{"title":"Beyond Juul: The New Face of Underage Nicotine Addiction - A Survey of College Students.","authors":"Griffin Riggs, Terry David Church","doi":"10.1007/s43441-024-00735-1","DOIUrl":"10.1007/s43441-024-00735-1","url":null,"abstract":"Background: Youth nicotine addiction is a major public health concern in the United States. Disposable Electronic Nicotine Delivery Systems (ENDS), or disposable vapes, are commonly sought out by youth despite not having received premarket authorization from the FDA. The objective of this study was to identify factors contributing to underage consumption of disposable ENDS.Methods: An anonymous survey was deployed to college students to understand young adults' perceptions and patterns of use of disposable ENDS.Results: Disposable ENDS are very popular among youth. The results of this study revealed the popular brands, flavors, modes of access, and attractive aspects of disposable ENDS. Survey results combined with information from the literature reveal that disposable ENDS gained popularity in the years following the decline in the popularity of pod-based ENDS, such as JUUL, following strict regulatory action from the FDA.Conclusion: To ultimately address underage nicotine addiction, the FDA must hold disposable ENDS to the same regulatory standards as other tobacco products and produce regulations specifically targeted at disposable ENDS. The results of this study emphasize the importance of making effective regulatory reform and functional educational resources to prevent young people from initiating the use of disposable ENDS.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"319-327"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: A Global Industry Survey on Post-Approval Change Management and Use of Reliance. 更正：一项关于批准后变更管理和信赖使用的全球行业调查。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 DOI: 10.1007/s43441-024-00733-3

Andrew Deavin, Aliyah Hossain, Isabelle Colmagne-Poulard, Kum Cheun Wong, Mónica Perea-Vélez, Sonia Cappellini, Susanne Ausborn, Sylvie Meillerais, Céline Bourguignon

引用次数: 0

Basic Considerations for Data Pooling Strategy in Multi-Regional Clinical Trials (MRCTs).

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2025-01-25 DOI: 10.1007/s43441-025-00744-8

Jiali Song, Chen Ji, Meng Chen, Jun Dong, Chao Zhu, Haiyan Wu, Wei Zhang, Kezhou Zhang, Bing Yu, Yun Wang, Hua Zhang, Fan Jia, Yan Hou

{"title":"Basic Considerations for Data Pooling Strategy in Multi-Regional Clinical Trials (MRCTs).","authors":"Jiali Song, Chen Ji, Meng Chen, Jun Dong, Chao Zhu, Haiyan Wu, Wei Zhang, Kezhou Zhang, Bing Yu, Yun Wang, Hua Zhang, Fan Jia, Yan Hou","doi":"10.1007/s43441-025-00744-8","DOIUrl":"10.1007/s43441-025-00744-8","url":null,"abstract":"The National Medical Products Administration of China has been implementing ICH E17, which describes the general principles for planning and designing of multi-regional clinical trials (MRCTs), yet there are several ambiguities in the execution and conduct remains in China or East Asia. In specific, pooling strategy, effect modifiers (EMs), statistical analysis, sample size allocation and their impact in alignment with global trial remains a challenge. In this paper, we explore on the criteria mentioned above under the context of China. EMs need to be determined and identified from intrinsic and extrinsic factors which might have the impact to the drug on specific populations. If no EMs are found, we use pooling by regions to understand whether differences across East Asian population exists, and whether pooling by East Asian is necessary. Statistical models used in the analysis are also listed to estimate the drug effect in pooled populations. In summary, this paper outlines the details of the MRCTs practices in China and provides better insights in practice both domestically and internationally for any future improvements.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"359-364"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Rule 11 on the European Medical Software Landscape: Analysis of EUDAMED and Further Databases Three Years After MDR Implementation.

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2025-01-28 DOI: 10.1007/s43441-025-00747-5

Arndt A Schmitz, Miriam Font-Nieves, Toumani Doucouré, Hans-Peter Podhaisky

{"title":"Impact of Rule 11 on the European Medical Software Landscape: Analysis of EUDAMED and Further Databases Three Years After MDR Implementation.","authors":"Arndt A Schmitz, Miriam Font-Nieves, Toumani Doucouré, Hans-Peter Podhaisky","doi":"10.1007/s43441-025-00747-5","DOIUrl":"10.1007/s43441-025-00747-5","url":null,"abstract":"Medicine is increasingly supported by software, with digital health technologies offering innovative ways to capture insights and drive therapies. Globally, medical device software must follow regulatory processes based on risk classification. The introduction of MDR represents a significant shift in risk-based classification for Medical Devices in Europe, including classification Rule 11 for software, which has caused significant discussions among European regulators. Three years after implementation, we conducted a systematic impact assessment of MDR classification Rule 11 for MDSW through a qualitative and quantitative analysis of over 2000 software entries from the European Medical Device database, complemented by data from other public databases such as the German DiGA directory and mHealthBELGIUM. Our results indicate that classification Rule 11 of the MDR results in a narrow bandwidth for class I software, whereas this used to be the most frequent classification for software under the MDD: while most of legacy software in EUDAMED falls in the lowest risk category as MDD Class I (53%), the situation reverses after the implementation of MDR with the most entries in Class IIa (55%). Analyzing the legacy MDD patient apps in Germany implies that three quarters will have to re-classify as MDR Class IIa at the end of the transition period in 2028. A comparison of the European and US regulatory landscapes, along with a systematic review of software features for Class I vs. Class IIa products, explains our findings and enables us to recommend a regulatory strategy for developing MDSW compliant with MDR Class I rules, ensuring fast access to the European market.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"365-378"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Risk-Based Quality Management: A Case for Centralized Monitoring. 基于风险的质量管理：集中监控的案例。

IF 2 4区医学

Therapeutic innovation & regulatory science Pub Date : 2025-03-01 Epub Date: 2024-12-11 DOI: 10.1007/s43441-024-00719-1

Nicole Stansbury, Danilo Branco, Cris McDavid, Jennifer Stewart, Kristin Surdam, Nycole Olson, Joanne Perry, Jeremy Liska, Linda Phillips, Amanda Coogan, Anina Adelfio, Lauren Garson

{"title":"Risk-Based Quality Management: A Case for Centralized Monitoring.","authors":"Nicole Stansbury, Danilo Branco, Cris McDavid, Jennifer Stewart, Kristin Surdam, Nycole Olson, Joanne Perry, Jeremy Liska, Linda Phillips, Amanda Coogan, Anina Adelfio, Lauren Garson","doi":"10.1007/s43441-024-00719-1","DOIUrl":"10.1007/s43441-024-00719-1","url":null,"abstract":"Since 2019, the Association of Clinical Research Organizations has conducted a landscape survey of risk based quality management (RBQM) adoption in clinical trials. Here, we present data from four years of surveys, with an emphasis on the most recent: the 2022 survey included data from 4958 trials across seven contract research organizations, of which 1004 were new studies started in 2022. Results indicate that while overall risk assessment adoption is strong, it is lagging in other risk-based components which suggests companies are not deriving the full expected benefits of performing a risk assessment and mitigation process to their trials. The 2022 study also suggests new study starts showing promising traction, with adoption hovering near 50% for most RBQM elements. At the same time, the survey suggests industry has mixed views on the potential value of quality tolerance limits (QTLs). Ultimately, centralized monitoring is being underutilized despite the potential of increased patient safety oversight and improved data quality. The authors of this paper developed a case study based on a trial in clinicaltrials.gov to demonstrate how RBQM adoption could include the key RBQM elements such as centralized monitoring, reduced source data review and source data verification as well as implementation of QTLs in a real-world scenario. The authors believe the clinical trial industry has an obligation to utilize centralized monitoring to produce more efficient and effective clinical trials and will make a case to do so in this paper.","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"199-210"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0