3/5-The Autism Biomarkers Consortium for Clinical Trials

3/5-自闭症临床试验生物标志物联盟

• 批准号: 10083890
• 负责人: Shafali Spurling Jeste
• 金额: $ 82.94万
• 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/10083890
• 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 warehouse; 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 自闭症生物标志物临床试验联盟的持续目标（ABC-CT）是建立 脑电图（EEG）和眼睛追踪（ET）生物标志物，可用于分层和/或AS 自闭症谱系障碍（ASD）临床试验中与社会功能有关的敏感和可靠的客观测定。 该更新应用程序旨在通过三项旨在的研究进一步验证承诺的测量 增强和扩展原始的ABC-CT研究：（1）对新队列中原始发现的确认研究 使用类似的设计（T1：基线，基线后T2：6周，基线后T3：24周）和样品 尺寸/特征（200，ASD为200，典型开发（TD）200）； （2）原始队列的后续研究 （n = 399）在原始ABC-CT入学后重新授予生物标志物和临床电池2.5 - 4年； （3）a 学龄前（3-5岁）儿童的平行脑电图和生物标志物的可行性研究（25岁，25岁，25岁 与TD）。生物标志物和临床电池使用良好的ASD测量社会通讯的关键方面 经过验证的范式适合预期的发展和认知范围。该研究将依靠 从第一阶段开始相同的领导力和五个合作实施站点（“站点”），所有经验丰富 在使用拟议的临床，EEG和ET方法的多站点协作临床研究中。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架构 整个财团，以确保有组织的数据管理，质量控制和可靠的上传到国家 自闭症研究数据库（NDAR）和NIH数据存储库。数据获取和分析核心 （DAAC）将监督科学标准和方法论严格的数据获取， 处理和分析。与联邦合作伙伴协调的行政核心 协议，将监督网站，DCC和DAAC的运营，以确保在方法论和道德上确保 严格，有效地完成研究的目的：1）在与新队列的确认研究中，评估是否是否 EEG和ET措施单独或结合使用，具有分层生物标志物和/或敏感的实用性， 可靠的临床试验变化测量； 2）在原始ABC-CT队列的后续研究中，评估 长期稳定性，对变化的敏感性以及标记的纵向预测价值； 3）可行性 研究，确定3-5岁儿童的潜在生物标志物的平行脑电图和ET的生存能力 与ASD和TD。将从参与者那里收集血液（DNA）样本，并从ASD和生物父母那里收集 将共享未来的基因组分析以及RAW，处理和分析的数据以创建社区资源 所有合格的调查人员都可以使用。这些目标旨在进一步发展有希望的 通过FDA生物标志物资格计划提高资格的生物标志物。