Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition. The lack of validated biomarkers for use in clinical trials is a significant problem for drug development in ASD and neurodevelopmental disorders. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) investigated electroencephalogram (EEG) and eye-tracking assays as potential biomarkers for clinical research. The study included 280 children with ASD and 119 with typical development (TD) between the ages of 6 to 11 years. Biomarker assays were collected at baseline (T1), six weeks (T2), and 24 weeks (T3). Interim analyses in a subset of 250 subjects indicated that an electrophysiological biomarker, the ?N170 to upright human faces,? demonstrated strong properties in terms of: (a) acquisition feasibility across sites and across key demographic and clinical factors; (b) appropriate distributional properties overall and at each timepoint (T1, T2) across and within diagnostic groups; (c) construct validity demonstrated by task-specific activation and signal strength in accordance with experimental manipulation in the TD group; (d) discriminant validity in terms of distinguishing between ASD and TD subjects; (e) test-retest reliability between T1 and T2 assays. Based on this evidence, a Letter of Intent (LOI) was submitted to the FDA Center for Drug Evaluation and Research (CDER) Biomarker Qualification Program. This LOI put forward the ?N170 to upright human faces? for a context-of- use as a diagnostic biomarker (identifying a biologically homogeneous subgroup within ASD) to enrich clinical trials by reduction of ASD-associated heterogeneity. The LOI was accepted into the FDA's Biomarker Qualification Program on May 6, 2019. The current application is submitted to support development of a Biomarker Qualification (BQ) Plan for the N170 latency measure. In response to the requirements of the FDA's BQ Plan outline and aligned with previous and planned (as per this cooperative agreement) discussions with the FDA, this proposal seeks to enhance empirical support for the biomarker with expanded analyses applied to the complete ABC-CT dataset and to refine the biomarker context-of-use in the process of developing a BQ Plan. The team of investigators has a successful record of collaboration and complementary expertise in electrophysiology, biostatistics, and the ASD clinical phenotype. The environments across sites have strong resources for the conduct of this work, and the methodological approach applies rigor unprecedented in ASD neuroscience research. Continued progress on a BQ Plan is a high impact objective for the field, as this innovative line of research represents the first potential biomarker for ASD. 1
There are no sensitive and objective ways to measure social function in autism spectrum disorder. Recent data from the Autism Biomarkers Consortium for Clinical Trials have led to acceptance of a Letter of Intent for an EEG biomarker in the FDA's Biomarker Qualification Program. This project involves additional data analyses and research to develop a Biomarker Qualification Plan for this indicator of social-communicative function.
