4/5-The Autism Biomarkers Consortium for Clinical Trials

项目总结/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 脑电描记术（EEG）和眼动追踪（ET）生物标志物，其可用于分层和/或作为脑电描记术（EEG）和眼动追踪（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测定。 这一延期申请旨在通过三项研究进一步验证有希望的措施， 增强和扩展原始ABC-CT研究：（1）在新队列中对原始发现进行确认研究 使用相似设计（T1：基线，T2：基线后6周，T3：基线后24周）和样本 大小/特征（200例ASD，200例典型发育（TD））;（2）原始队列的随访研究 （N=399）在初始ABC-CT入组后2.5-4年重新给予生物标志物和临床组合;（3）a 在学龄前（3-5岁）儿童（25名ASD，25名 TD）。生物标志物和临床电池测量ASD中社交沟通的关键方面， 适用于预期发展和认知范围的验证范式。这项研究将依赖于 相同的领导层和第一阶段的五个协作实施站点（“站点”），所有站点都经验丰富 在多站点协作临床研究中使用所提出的临床、EEG和ET方法。数据 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 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数据库。数据采集和分析核心 （DAAC）将监督科学标准的一致使用和数据采集方法的严格性， 处理和分析。行政中心与该合作社的联邦伙伴协调， 协议，将监督网站，DCC和DAAC的运营，以确保方法和道德 严格、有效地完成研究目标：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，具有作为分层生物标志物的效用和/或敏感性， 临床试验中变化的可靠指标; 2）在原始ABC-CT队列的随访研究中，评估 长期稳定性、变化敏感性和纵向预测价值; 3）在可行性方面， 研究，确定并行EEG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。血液（DNA）样本将从ASD受试者和生物学父母中采集， 未来的基因组分析，以及原始的、经过处理和分析的数据将被共享，以创建社区资源 所有合格的研究者均可使用。这些目标旨在进一步发展有前途的 生物标志物，以推进FDA生物标志物资格认证计划的资格认证。

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.