The Autism Biomarkers Consortium for Clinical Trials

 描述(由申请人提供)：该联盟的目标是建立可在自闭症谱系障碍(ASD)临床试验中用作生物标记物和/或敏感和可靠的社会损害客观分析的工具。具体地说，我们的目标是通过验证(A)将是对治疗和EEG反应的敏感和可靠评估的结果指标和(B)可用于通过分层减少样本的异质性、指示早期疗效和/或展示目标参与的眼球跟踪(ET)生物标记物，来加速ASD社会损害的有效治疗的开发。该联盟将对患有自闭症和典型发育障碍(TD)的学龄前(3-5岁)和学龄儿童(6-11岁)进行一项自然主义的纵向研究，智商从50到115不等。儿童将接受三个时间点(T1：基线，T2：6周，T3：24周)的评估，使用临床医生、照顾者和基于实验室的(LB)社会损害衡量标准，以及一系列概念上相关的EEG和ET任务以及临床状态的独立评级。这一组合使用适合于这一发展和认知范围的经过充分验证的范例来衡量自闭症社交的关键方面。五个协作实施站点(“站点”)将在招募、筛查、诊断、测试和纵向评估方面做出同样的贡献，这些站点都在使用本文提出的典型和非典型开发方法进行多站点协作临床研究方面经验丰富。数据协调核心(DCC)将提供一个安全的信息基础设施，以简化整个联合体的通信和数据流，以确保有组织、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数据储存库。数据采集和分析核心(DAAC)将监督对标准化数据收集、处理和分析的科学标准和方法严格性的一致应用。管理核心将监督站点、DCC和DAAC的运作，以在此合作协议中与联邦和私人合作伙伴协调：1)比较社会功能障碍评估与临床医生和照顾者评估是否为临床状态的更敏感指标；2)评估这套 ET和EEG单独或联合测量在临床试验中作为分层生物标记物和/或敏感和可靠的变化测量、评估生存能力具有潜在的实用价值。 在以下方面：结构效度；重测信度、一致性和稳定性；判别效度；收敛效度；以及对变化的敏感性；3)采集自闭症受试者和受试者父母的血液(DNA)样本，用于未来的基因组分析，并分享原始、处理和分析的数据，以创建一个社区资源，供所有合格的研究人员使用。

 DESCRIPTION (provided by applicant): 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.