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用作自闭症谱系障碍（ASD）临床试验中社交障碍的生物标志物和/或敏感可靠的客观测定的工具。具体而言，我们的目标是通过验证（a）对治疗和EEG反应进行敏感和可靠评估的结局指标，以及（B）可用于通过分层减少样本异质性、指示早期疗效和/或证明靶点参与的眼动追踪（ET）生物标志物，加速ASD社交障碍有效治疗的开发。该联盟将对学龄前（3-5岁）和学龄（6-11岁）ASD和典型发育（TD）儿童进行自然纵向研究，智商范围为50-115。将在三个时间点（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（LB）的社交障碍测量，沿着一系列概念相关的EEG和ET任务以及临床状态的独立评级，对儿童进行评估。该电池测量ASD中社交沟通的关键方面，使用适用于此发育和认知范围的经过充分验证的范例。五个协作实施中心（“中心”）均在典型和非典型开发中使用本文提出的方法进行多中心协作临床研究方面经验丰富，将对招募、筛选、诊断、检测和纵向评估做出同等贡献。数据协调核心（DCC）将提供一个安全的信息学基础设施，以简化整个联盟的通信和数据流，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数据库。数据采集和分析核心（DAAC）将监督科学标准的一致应用和标准化数据收集，处理和分析的方法论严谨性。行政核心将监督研究中心、DCC和DAAC的运作，以与本合作协议中的联邦和私人合作伙伴协调：1）比较LB测量与临床医生和护理人员对社会损害的评估是否是临床状态的更敏感指标; 2）评价这组评估是否符合临床状况的要求。 ET和EEG测量，单独或组合，作为分层生物标志物和/或临床试验中变化的敏感和可靠测量，评估生存能力， 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;和变化敏感性; 3）从受试者和ASD受试者的父母收集血液（DNA）样品用于未来的基因组分析，并共享原始、处理和分析的数据以创建可供所有合格的研究者使用的社区资源。

 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.