Therapeutic innovation & regulatory science最新文献

{"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":"https://doi.org/10.1007/s43441-024-00729-z","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>A reference set was developed using the safety information of drugs approved in Japan to promote research on data-mining methods.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-21","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}

{"title":"Consumer Understanding of Prescription Drug Indications in Direct-to-Consumer Television Advertisements.","authors":"Helen W Sullivan, Kathryn J Aikin, Mihaela Johnson, Kate Ferriola-Bruckenstein","doi":"10.1007/s43441-024-00732-4","DOIUrl":"https://doi.org/10.1007/s43441-024-00732-4","url":null,"abstract":"<p><strong>Background: </strong>Prescription drugs may be indicated to treat more than one medical condition, and companies may promote more than one indication in the same direct-to-consumer (DTC) ad. This study examined how presenting multiple prescription drug indications in one DTC television ad affects consumers' processing of drug information.</p><p><strong>Methods: </strong>We conducted two studies with adults diagnosed with diabetes (Study 1, N = 408) or rheumatoid arthritis (Study 2, N = 411). We randomly assigned participants to view one of three television ads: primary indication only (Study 1: diabetic peripheral neuropathy; Study 2: rheumatoid arthritis), primary plus a similar secondary indication (Study 1: fibromyalgia; Study 2: psoriatic arthritis), or primary plus a dissimilar secondary indication (Study 1: generalized anxiety disorder; Study 2: ulcerative colitis).</p><p><strong>Results: </strong>Remembering and understanding the primary indication was not significantly affected by the presence of a secondary indication (similar or dissimilar). Higher health literacy participants remembered and understood secondary indications.</p><p><strong>Conclusions: </strong>Including a second indication in DTC television ads does not appear to have detrimental effects and can increase awareness of the second indication for some participants. Industry and regulators should continue to ensure DTC promotion is truthful and non-misleading, irrespective of the number of indications presented.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865540","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}

{"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":"https://doi.org/10.1007/s43441-024-00720-8","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-17","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}

{"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":"https://doi.org/10.1007/s43441-024-00708-4","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-13","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}

{"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":"https://doi.org/10.1007/s43441-024-00719-1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data Monitoring Committee Reports: Telling the Data's Story.","authors":"Lijuan Zeng, Toshimitsu Hamasaki, Scott R Evans","doi":"10.1007/s43441-024-00727-1","DOIUrl":"https://doi.org/10.1007/s43441-024-00727-1","url":null,"abstract":"<p><p>A Data Monitoring Committee (DMC) plays a pivotal role in monitoring participant safety and efficacy and overseeing the integrity of clinical trials. DMCs accomplish this mission by periodically reviewing accumulating data to assess benefits and harms of interventions in ongoing studies and making subsequent recommendations regarding future clinical trial conduct to the trial sponsor. Reports summarizing data from the clinical trial are prepared for the DMC by statistical and data analysis centers to inform DMC decision-making. In practice however, these reports are often disorganized, complex, and provide overwhelming detail yet insufficient information, that hinders accurate and efficient interpretation of interim data. This review paper delves into the nuances of preparing effective DMC reports, highlighting the importance of simplicity, clarity, and thoughtful relevance in data presentation. We discuss structured approaches for preparing closed reports, which deal with sensitive and sometimes messy interim data, and underscore the use of visual summaries and narrative elements that enhance comprehension and facilitate efficient assessments of trial data. The paper outlines key principles for preparing DMC reports and provides practical guidance on their structure. Ultimately, this guidance seeks to ensure that the data's story is clearly and efficiently conveyed to facilitate the DMC decision-making process.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802263","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}

{"title":"Call for Papers: The Inflation Reduction Act and Its Impact on Innovation, Access, and Affordability.","authors":"Gregory Daniel","doi":"10.1007/s43441-024-00721-7","DOIUrl":"https://doi.org/10.1007/s43441-024-00721-7","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792387","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}

{"title":"Efficient Positioning of QTL and Secondary Limit Thresholds in a Clinical Trial Risk-Based Monitoring.","authors":"Vladimir Shnaydman","doi":"10.1007/s43441-024-00722-6","DOIUrl":"https://doi.org/10.1007/s43441-024-00722-6","url":null,"abstract":"<p><p>In the high-stakes world of clinical trials, where a company's multimillion-dollar drug development investment is at risk, the increasing complexity of these trials only compounds the challenges. Therefore, the development of a robust risk mitigation strategy, as a crucial component of comprehensive risk planning, is not just important but essential for effective drug development, particularly in the RBQM (Risk-Based Quality Management) ecosystem and its component-RBM (Risk-Based Monitoring). This emphasis on the urgency and significance of risk mitigation strategy can help the audience understand the gravity of the topic. The paper introduces a novel modeling framework for deriving an efficient risk mitigation strategy at the planning stage of a clinical trial and establishing operational rules (thresholds) under the assumption that contingency resources are limited. The problem is solved in two steps: (1) Deriving a contingency budget and its efficient allocation across risks to be mitigated and (2) Deriving operational rules to be aligned with risk assessment and contingency resources. This approach is based on combining optimization and simulation models. The optimization model aims to derive an efficient contingency budget and allocate limited mitigation resources across mitigated risks. The simulation model aims to efficiently position each risk's QTL/KRI (Quality Tolerance Limits/Key Risk Indicators at a clinical trial level) and Secondary Limit thresholds. A case study illustrates the proposed technique's practical application and effectiveness. This example demonstrates the framework's potential and instills confidence in its successful implementation, reassuring the audience of its practicality and usefulness. The paper is structured as follows. (1) Introduction; (2) Methodology; (3) Models-Risk Optimizer and Risk Simulator; (4) Case study; (5) Discussion and (6) Conclusion.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787181","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}

{"title":"Research on Core Competency Elements of Clinical Investigators.","authors":"Xin Wang, Shuang Zhao, Han Yang, Miao Miao, Siwei An, Wenbing Yao","doi":"10.1007/s43441-024-00688-5","DOIUrl":"https://doi.org/10.1007/s43441-024-00688-5","url":null,"abstract":"<p><strong>Background: </strong>To construct a competency model for clinical investigators involved in the process of new drug development, providing a reference for the training, selection and assessment of clinical investigators.</p><p><strong>Methods: </strong>The Behavioral Event Interview (BEI) method was used to interview 12 excellent clinical investigators and 8 clinical investigators of average performance. Each competency characteristic was extracted from the interview text by semantic coding. Total frequency, total score, average score and highest score were calculated for each competency element. Category agreement coefficient, coefficient of reliability and Spearman correlation coefficient were used to assess the consistency of two coders for coding and classification. Independent-samples Mann-Whitney U test was applied to compare the differences in competency elements between the group of excellent clinical investigators and the group of average investigators.</p><p><strong>Results: </strong>The average coefficient of category agreement was 0.671, and the average coefficient of reliability was 0.803. No significant differences were observed between the two groups in the aspect of interview time (P = 0.190) and the interview words (P = 0.184), indicating comparability between the two groups. However, there was a clear performance difference between the excellent and average groups. In addition, we found that the competency model for clinical investigators contained 24 prominent competence elements and 8 benchmark competency elements.</p><p><strong>Conclusions: </strong>Clinical investigator is a medical professional who is involved in a highly research-intensive and practical job, where prominent competency element largely reflects clinical practice skills, innovation and awareness of Good Clinic Practice (GCP). Our results provide a reference for assessing clinical investigators' competencies, encouraging and guiding them to modify their behaviors according to the competency model, and also cultivating clinical investigators so as to improve the competence level of clinical investigators.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751669","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}

{"title":"Review of the European Union Clinical Trials Regulation: Key Early Learnings from the United Kingdom Drug Information Association Medical Writing Committee.","authors":"Dicken D H Koo, Eve Taylor, Iain T Hooper, Saman F Khaled, Vivien Fagan, Helen Turner, Harriet L Buttery","doi":"10.1007/s43441-024-00726-2","DOIUrl":"https://doi.org/10.1007/s43441-024-00726-2","url":null,"abstract":"<p><p>The European Union Clinical Trials Regulation (EU CTR) provides new regulatory requirements for the preparation and submission of clinical trial documents. The United Kingdom Drug Information Association Medical Writing (UK DIA MW) Committee, with members from across the pharmaceutical industry, have reviewed the EU CTR and in this report, provide expert guidance on writing documents for submission in the EU CTR Clinical Trials Information System (CTIS) portal. Medical writers should be aware that the Investigator's Brochure containing the Reference Safety Information (RSI) must align with the annual safety report, and the RSI format must comply closely with the EU CTR. For clinical study protocols, medical writers should prepare a single integrated EU protocol that receives consolidated approvals from all participating EU member states, with different versions of a protocol for different EU member states no longer permitted. This report also provides details of experiences and recommendations on protocol synopses from the UK DIA MW Committee. In addition, plain language summaries are new EU CTR documents required for each study presenting summaries of clinical trial results for laypersons. Some of these documents will be published in the publicly accessible CTIS portal which has created concerns amongst many companies who are keen to protect commercially confidential information (CCI). Medical writers may help reduce CCI through lean writing, but specifically identifying CCI may require specialist legal evaluation. This report by the UK DIA MW Committee highlights the key processes for medical writers to ensure compliance with the EU CTR when preparing documents for submission to the CTIS portal.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751671","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}