2/5-The Autism Biomarkers Consortium for Clinical Trials

2/5-自闭症生物标志物临床试验联盟

• 批准号: 10439669
• 负责人: CHARLES Alexander NELSON
• 金额: $ 91.4万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-17 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439669
• 关键词: 5 year old; Biological; Biological Assay; Biological Markers; Blood; Characteristics; Child; Clinical; Clinical Research; Clinical Trials; Cognitive; Communication; Communities; DNA; Data; Data Analyses; Data Collection; Databases; Detection; Development; Diagnostic; Discrimination; Electroencephalography; Enrollment; Ensure; Ethics; Exhibits; Face; Feasibility Studies; Follow-Up Studies; Future; Genomics; Goals; Heterogeneity; Human; Individual; Leadership; Measurement; Measures; Methodology; National Institute of Mental Health; Neurodevelopmental Disorder; Nursery Schools; Parents; Participant; Pattern; Phase; Predictive Value; Process; Property; Psychometrics; Quality Control; Research; Research Design; Research Personnel; Resources; Sample Size; Sampling; Sampling Studies; Secure; Site; Social Functioning; Stratification; Testing; Time; U-Series Cooperative Agreements; United States National Institutes of Health; Work; aged; autism spectrum disorder; autistic children; base; clinical trial enrollment; cohort; data acquisition; data integration; data management; data repository; design; experience; indexing; informatics infrastructure; middle childhood; oculomotor; operation; potential biomarker; programs; social communication; visual tracking

Project Summary/Abstract The ongoing goal of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is to establish electroencephalography (EEG) and eye-tracking (ET) biomarkers that can be used for stratification and/or as sensitive and reliable objective assays related to social function in autism spectrum disorder (ASD) clinical trials. This renewal application seeks to further validate promising measures through three studies designed to enhance and extend the original ABC-CT study: (1) a confirmation study of the original findings in a new cohort using similar design (T1: Baseline, T2: 6 weeks post baseline, T3: 24 weeks post baseline) and sample size/characteristics (200 with ASD, 200 with typical development (TD)); (2) a follow-up study of the original cohort (N=399) to re-administer the biomarker and clinical batteries 2.5-4 years after original ABC-CT enrollment; (3) a feasibility study of parallel EEG and ET biomarkers in preschool-aged (3-5-year-old) children (25 with ASD, 25 with TD). The biomarker and clinical batteries measure key facets of social-communication in ASD using well- validated paradigms appropriate for the intended developmental and cognitive range. The study will rely on the same leadership and five Collaborating Implementation Sites (“Sites”) from the first phase, all highly experienced in multi-site collaborative clinical research using the proposed clinical, EEG, and ET methodologies. The Data Coordinating Core (DCC) will provide a secure informatics infrastructure for communication and data integration across the consortium to ensure organized data management, quality control, and reliable upload to the National Database for Autism Research (NDAR) and NIH Data Repositories. The Data Acquisition and Analysis Core (DAAC) will oversee consistent use of scientific standards and methodological rigor for data acquisition, processing, and analytics. The Administrative Core, in coordination with federal partners in this cooperative agreement, will oversee the operations of the sites, DCC, and DAAC to ensure methodologically and ethically rigorous, efficient completion of study aims: 1) In the confirmation study with a new cohort, evaluate whether EEG and ET measures, individually or in combination, have utility as stratification biomarkers and/or sensitive, reliable measures of change in clinical trials; 2) In the follow-up study of the original ABC-CT cohort, assess long-term stability, sensitivity to change, and longitudinal predictive value of the markers; 3) In the feasibility study, determine the viability of parallel EEG and ET measures as potential biomarkers in 3-5-year-old children with ASD and TD. Blood (DNA) samples will be collected from participants with ASD and biological parents for future genomic analyses, and raw, processed, and analyzed data will be shared to create a community resource accessible for use by all qualified investigators. These objectives are designed to further develop promising biomarkers to advance qualification with the FDA Biomarker Qualification Program.

项目摘要/摘要 自闭症临床试验生物标记物联盟(ABC-CT)的持续目标是建立 可用于分层和/或AS的脑电(EEG)和眼球跟踪(ET)生物标志物 在自闭症谱系障碍(ASD)临床试验中，与社会功能相关的敏感和可靠的客观分析。 这份续签申请旨在通过三项研究进一步验证有前景的措施 加强和扩展最初的ABC-CT研究：(1)对新队列中最初发现的确证研究 使用类似的设计(T1：基线，T2：基线后6周，T3：基线后24周)和样本 大小/特征(200人患有自闭症，200人有典型发育(TD))；(2)对原始队列的后续研究 (n=399)在最初的ABC-CT登记后2.5-4年重新管理生物标志物和临床电池；(3)a 学龄前(3-5岁)儿童(25例ASD，25例)并行EEG和ET生物标志物的可行性研究 与TD)。生物标记物和临床电池使用Well-MARKER来测量ASD中社交沟通的关键方面 经过验证的范例适合预期的发展和认知范围。这项研究将依靠 相同的领导力和第一阶段的五个协作实施站点(“站点”)，均经验丰富 在使用建议的临床、EEG和ET方法的多地点协作临床研究中。数据 协调核心(DCC)将为通信和数据集成提供安全的信息基础设施 整个联合体确保有组织的数据管理、质量控制和可靠的上载到National 自闭症研究数据库(NDAR)和美国国立卫生研究院数据库。数据采集与分析核心 (DAAC)将监督数据收集的科学标准和方法严格性的一致使用， 处理和分析。行政核心，与该合作社的联邦合作伙伴协调 协议，将监督现场、DCC和DAAC的运作，以确保在方法和道德上 严格、高效地完成研究目标：1)在新队列的确认性研究中，评估是否 单独或组合的EEG和ET测量作为分层生物标记物和/或敏感性， 临床试验变化的可靠措施；2)在最初的ABC-CT队列的随访研究中，评估 标记物的长期稳定性、变化敏感性和纵向预测值；3)可行性 研究，确定并行的脑电和ET测量作为3-5岁儿童潜在生物标志物的可行性 ASD和TD。将从患有自闭症的参与者和亲生父母那里采集血液(DNA)样本，用于 未来的基因组分析，以及原始、处理和分析的数据将被共享，以创建社区资源 可供所有合格的调查人员使用。这些目标旨在进一步发展有前途的 生物标记物通过FDA生物标记物资格认证计划进行资格认证。