Biomarker Acquisition and Quality Control for Multi-Site Studies: The Autism Biomarkers Consortium for Clinical Trials

Abstract

The objective of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is to evaluate a set of lab-based behavioral video tracking (VT), electroencephalography (EEG), and eye tracking (ET) measures for use in clinical trials with children with autism spectrum disorder (ASD). Within the larger organizational structure of the ABC-CT, the Data Acquisition and Analytic Core (DAAC) oversees the standardization of VT, EEG, and ET data acquisition, data processing, and data analysis. This includes designing and documenting data acquisition and analytic protocols and manuals; facilitating site training in acquisition; data acquisition quality control (QC); derivation and validation of dependent variables (DVs); and analytic deliverables including preparation of data for submission to the National Database for Autism Research (NDAR). To oversee consistent application of scientific standards and methodological rigor for data acquisition, processing, and analytics, we developed standard operating procedures that reflect the logistical needs of multi-site research, and the need for well-articulated, transparent processes that can be implemented in future clinical trials. This report details the methodology of the ABC-CT related to acquisition and QC in our Feasibility and Main Study phases. Based on our acquisition metrics from a preplanned interim analysis, we report high levels of acquisition success utilizing VT, EEG, and ET experiments in a relatively large sample of children with ASD and typical development (TD), with data acquired across multiple sites and use of a manualized training and acquisition protocol.

Day-to-Day Test-Retest Reliability of EEG Profiles in Children With Autism Spectrum Disorder and Typical Development

“…These data were collected as part of the ongoing Autism Biomarkers Consortium for Clinical Trials (ABC-CT 1 ; McPartland, 2016). Details of the ABC-CT data acquisition are reported elsewhere (Webb et al, 2019;McPartland et al, 2020). The objective of the ABC-CT is to evaluate a set of electrophysiological (EEG), eye-tracking, and behavioral measures for use in clinical trials for ASD.…”

“…In the feasibility phase of the ABC-CT, EEG acquisition included six paradigms (Webb et al, 2019), with ''Resting EEG eyes open during calm viewing'' of silent, chromatic digital videos (similar to screensavers) collected twice on two separate days. Video stimuli consisted of six 30 s non-social abstract videos purchased from Shutterstock, which were presented to the participant in random order in three blocks of 1 min on each day (Webb et al, 2018).…”

The Autism Biomarkers Consortium for Clinical Trials (ABC-CT): Scientific Context, Study Design, and Progress Toward Biomarker Qualification

“…Identical equipment was used for EEG (EGI 128 channel system) and ET (SR Research EyeLink System) data acquisition and processing at all five data collection sites; equipment was installed and tested by a central data acquisition team to ensure identical setup parameters. Detailed manuals of procedures (MOPs) were established for all biomarker paradigms and standardized protocols were adopted for data collection, processing, and analysis (Webb et al, 2020). Likewise, MOPs guided clinical data collection, and all staff underwent comprehensive training, addressing participant screening, clinical measurement, biomarker data collection procedures, data entry, and study management processes.…”

“…After a series of in-person meetings and teleconferences involving project governance, a feasibility study of 25 children with ASD and 26 TD children was conducted between December 2015 and March 2016. Based on results of the Feasibility Study, the Main Study design (described in this manuscript) was finalized (for details of review of feasibility and transition to main study, see Webb et al, 2020, sections 2.6 and 2.7). The first subject in the Main study was enrolled in October 2016, data collection was completed in May 2019, and final analyses of the complete data set are in progress, with planned dissemination in Spring 2020.…”

Within Visit Test-Retest Reliability of EEG Profiles in Children with Autism Spectrum Disorder and Typical Development

“…Groups differed significantly on age (t(45) = 2.3, p = .025) and IQ (t(45) = 4.6, p <.001) The “Feasibility Study Visit” consisted of two EEGs on two separate days (termed here “Day 1” and “Day 2”), separated by a short window of time (range 1-22 days, median 6 days) during this phase. Participants were characterized using rigorous autism diagnostic standardized measures (Autism Diagnostic Observation Schedule, 2 nd edition (ADOS-2), 19 Autism Diagnostic Interview - Revised (ADI-R), 20 and Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria 21 ) by research-reliable clinicians 22 , and cognitive measures Differential Ability Scales 2 nd edition (DAS-II). 23…”