4/5-The Autism Biomarkers Consortium for Clinical Trials

4/5-自闭症生物标志物临床试验联盟

• 批准号: 10439671
• 负责人: Natalia M Kleinhans
• 金额: $ 91.5万
• 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/10439671
• 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.

项目概要/摘要 自闭症生物标志物临床试验联盟 (ABC-CT) 的持续目标是建立 脑电图 (EEG) 和眼动追踪 (ET) 生物标志物可用于分层和/或作为 在自闭症谱系障碍 (ASD) 临床试验中与社会功能相关的敏感且可靠的客观测定。 该更新申请旨在通过三项研究来验证进一步有希望的措施，旨在 加强和扩展原来的ABC-CT研究：（1）在新队列中对原来的研究结果进行确认研究 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 规模/特征（200 名患有 ASD，200 名患有典型发育（TD））；（2）原始队列的后续研究 (N=399) 在最初 ABC-CT 登记后 2.5-4 年后重新施用生物标志物和临床电池；(3) 学龄前（3-5 岁）儿童（25 名患有自闭症谱系障碍（ASD）、25 名 生物标志物和临床电池使用良好的方法来测量 ASD 社交沟通的关键方面。 适合预期发展和认知范围的经过验证的范式。 与第一阶段相同的领导层和五个合作实施地点（“地点”），全部经验丰富 使用所提出的临床、脑电图和 ET 方法进行多站点协作临床研究。 协调核心（DCC）将为通信和数据集成提供安全的信息学基础设施 整个联盟，以确保有组织的数据管理、质量控制以及可靠地上传到国家 自闭症研究数据库 (NDAR) 和 NIH 数据存储库数据采集和分析核心。 (DAAC) 将监督数据采集的科学标准和方法要求的一致使用， 行政核心，与该合作中的联邦合作伙伴协调。 协议，将监督站点、DCC 和 DAAC 的运营，以确保在方法上和道德上 严格、高效地完成研究目标： 1) 在新队列的确认研究中，评估是否 EEG 和 ET 测量，单独或组合，可用作分层生物标志物和/或敏感、 临床试验中变化的可靠衡量标准；2) 在原始 ABC-CT 队列的后续研究中，评估 标记物的长期稳定性、变化敏感性和纵向预测价值 3) 可行性； 研究，确定平行 EEG 和 ET 测量作为 3-5 岁儿童潜在生物标志物的可行性 将从患有 ASD 和 TD 的参与者和亲生父母那里收集血液 (DNA) 样本。 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 这些目标可供所有合格的研究人员使用，旨在进一步开发有前景的产品。 生物标志物，以提高 FDA 生物标志物资格计划的资格。