The Autism Biomarkers Consortium for Clinical Trials

项目总结/摘要 该联盟的目标是建立可用作生物标志物和/或敏感可靠的工具。 自闭症谱系障碍（ASD）临床试验中社会损害的客观分析。具体而言，我们的目标是 通过验证（a）结果，加速开发有效的ASD社交障碍治疗方法 对治疗和EEG的反应进行敏感和可靠评估的措施，以及（B）眼跟踪 (ET)可用于通过分层降低样品异质性的生物标志物，指示早期功效， 和/或显示目标接合。该联盟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）ASD儿童和典型发育（TD）儿童 从50到115。儿童将在三个时间点进行评估（T1：基线，T2：6周，T3：24 周），使用临床医生、护理人员和基于实验室的（LB）社交障碍测量，以及一组 概念上相关的EEG和ET任务和临床状态的独立评级。这是电池测量的关键 ASD中社会沟通的各个方面，使用适用于这种发展和 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本文提出的方法进行协作临床研究， 将同样有助于招募、筛选、诊断、测试和纵向评估。数据 协调核心（DCC）将提供一个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，以确保有组织的、安全的数据管理、质量控制和可靠的 上传到国家自闭症研究数据库和NIH/NIMH数据库。数据采集 DAAC将监督科学标准的一致应用和方法的严格性 用于标准化数据收集、处理和分析。行政核心将监督这些行动 各研究中心、DCC和DAAC与联邦和私人合作伙伴协调合作 同意：1）比较LB是否测量与临床医生和护理人员的社会评估 损伤是临床状态的更敏感的指标; 2）评估这组ET和EEG测量， 单独或组合，具有作为分层生物标志物的潜在效用和/或敏感和可靠的 临床试验变化的测量，评估可行性：结构效度;重测信度， 一致性和稳定性;判别效度;收敛效度;和变化敏感性; 3）收集血液 (DNA)来自受试者和ASD受试者父母的样本用于未来的基因组分析， 处理和分析数据，以创建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.