Abstract
Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with ASD and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA’s Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.
Highlights
There are currently no validated biomarkers for use in clinical trials in autism spectrum disorder (ASD)
We describe specific elements of Autism Biomarkers Consortium for Clinical Trials (ABC-CT) study design intended to address the aforementioned challenges for biomarker development in ASD, as well as additional features of the study innovated for this purpose
Building upon a strong foundation of prior research that has put forward candidate markers, the ABC-CT has advanced understanding by innovating in terms of study design and scope
Summary
There are currently no validated biomarkers for use in clinical trials in autism spectrum disorder (ASD). Few biomarker studies have included multiple sampling points in a longitudinal design, preventing inference regarding the stability of measurement in a person over time (i.e., test-retest reliability, developmental stability) This is critical information for the potential use of biomarkers in clinical trials. The N170 biomarker showed strong performance in terms of reliable and valid data acquisition and demonstration of predicted between-group differences at interim analyses conducted in April 2018 Based on these results, a Letter of Intent (LOI) for the N170 latency to upright human faces was submitted to the FDA’s Center for Drug Evaluation and Research Biomarker Qualification Program (BQP) in November, 2018; the proposed context of use was identifying a biologically homogeneous subgroup within ASD to enrich clinical trials by reduction of ASD-associated heterogeneity. Given the centrality of other sensory modalities (e.g., audition) to social-communication, investigation of these modalities is warranted
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