4/5-The Autism Biomarkers Consortium for Clinical Trials

项目摘要/摘要 该联盟的目标是建立可用作生物标志物和/或敏感和可靠的工具 目的研究自闭症谱系障碍(ASD)临床试验中的社会功能障碍。具体来说，我们的目标是 通过验证(A)结果，加速开发自闭症社会功能障碍的有效治疗方法 将对治疗和脑电反应进行敏感和可靠评估的措施和(B)眼球跟踪 (ET)生物标志物，可用于通过层析降低样品的异质性，表明早期疗效， 和/或展示目标参与度。该财团将进行一项自然主义的纵向研究 学龄前(3-5岁)和学龄期(6-11岁)患有自闭症和典型发育(TD)智商的儿童 从50到115不等。将在三个时间点(T1：基线，T2：6周，T3：24)对儿童进行评估 使用临床医生、护理者和基于实验室的(LB)社会损害测量，以及一组 概念上相关的EEG和ET任务以及临床状态的独立评级。这块电池能测量钥匙 在ASD中使用适用于这种发展和发展的经过充分验证的范例的社交沟通方面 认知范围。五个协作实施站点(“站点”)，均在多站点方面经验丰富 在典型和非典型开发中使用这里提出的方法进行的协作临床研究， 将对招募、筛选、诊断、测试和纵向评估做出同样的贡献。数据 协调核心(DCC)将提供安全的信息基础设施，以简化通信和数据 在整个联合体中流动，以确保组织、安全的数据管理、质量控制和可靠 上传到国家自闭症研究数据库和NIH/NIMH数据仓库。数据采集 分析核心(DAAC)将监督科学标准和方法严格性的一致应用 用于标准化的数据收集、处理和分析。行政核心将监督业务运作 在这些地点中，DCC和DAAC在这个合作社中与联邦和私人合作伙伴进行协调 同意：1)比较LB措施与临床医生和照顾者对社会的评估 损害是临床状态更敏感的指标；2)评估这套ET和EEG测量， 单独或组合，具有作为分层生物标志物和/或敏感和可靠的潜在用途 临床试验变化的衡量标准，从以下方面评估生存能力：结构效度；重测可靠性； 一致性和稳定性；区分效度；收敛效度；对变化的敏感度；3)采集血液 (DNA)来自自闭症受试者和自闭症受试者父母的样本，用于未来的基因组分析，并分享原始的， 对数据进行处理和分析，以创建一个可供所有合格调查人员使用的社区资源。

Project Summary/Abstract The goal of this consortium is to establish tools that can be used as biomarkers and/or sensitive and reliable objective assays of social impairment in autism spectrum disorder (ASD) clinical trials. Specifically, we aim to accelerate the development of effective treatments for social impairment in ASD by validating (a) outcome measures that will be sensitive and reliable assessments of response to treatment and EEG and (b) eye-tracking (ET) biomarkers that can be used to reduce heterogeneity of samples via stratification, indicate early efficacy, and/or demonstrate target engagement. The consortium will conduct a naturalistic, longitudinal study of preschool (3-5 years) and school aged (6-11 years) children with ASD and typical development (TD) with IQ ranging from 50-115. Children will be assessed across three time points (T1: Baseline, T2: 6 weeks, T3: 24 weeks) using clinician, caregiver and lab-based (LB) measures of social impairment, along with a battery of conceptually related EEG and ET tasks and independent ratings of clinical status. This battery measures key facets of social-communication in ASD using well-validated paradigms appropriate for this developmental and cognitive range. Five Collaborating Implementation Sites (“Sites”), all highly experienced in multi-site collaborative clinical research using the methodologies proposed here in both typical and atypical development, will contribute equally to recruitment, screening, diagnosis, testing, and longitudinal assessment. The Data Coordinating Core (DCC) will provide a secure informatics infrastructure to streamline communication and data flow throughout the consortium to ensure organized, secure data management, quality control, and reliable upload to the National Database for Autism Research and NIH/NIMH Data Repositories. The Data Acquisition and Analysis Core (DAAC) will oversee consistent application of scientific standards and methodological rigor for standardized data collection, processing, and analytics. The Administrative Core will oversee the operations of the Sites, the DCC, and the DAAC to coordinate with federal and private partners in this cooperative agreement to: 1) Compare whether LB measures versus clinician and caregiver assessments of social impairment are more sensitive indicators of clinical status; 2) Evaluate whether this set of ET and EEG measures, individually or in combination, has potential utility as stratification biomarkers and/or sensitive and reliable measures of change in clinical trials, assessing viability in terms of: construct validity; test-retest reliability, consistency, and stability; discriminant validity ; convergent validity; and sensitivity to change; 3) Collect blood (DNA) samples from subjects and parents of ASD subjects for future genomic analyses and share raw, processed, and analyzed data to create a community resource accessible for use by all qualified investigators.