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The Autism Biomarkers Consortium for Clinical Trials: Study Design and Progress to Interim Analysis
Recent scientific advances offer promise for the development of targeted treatment methods to improve social-communication in autism spectrum disorder (ASD). The promise of targeted treatments is hindered by a lack of reliable and sensitive objective measures to identify subgroups likely to respond to specific treatments, to rapidly assess response to treatment, and to evaluate whether a treatment has affected the intended target. The Autism Biomarkers Consortium for Clinical Trials is a multisite biomarker development study designed to advance these objectives.
Objectives:
The goals of the ABC-CT are to: (1) establish sensitive and reliable objective EEG, eye-tracking (ET), and lab-based behavioral assays of social communication in ASD for predicting and quantifying response to treatment, reducing heterogeneity of samples via stratification, indicating early efficacy, and demonstrating target engagement; (2) create a publicly accessible repository spanning genetics, biomarkers, and clinical and behavioral information; and (3) establish an infrastructure optimized for the conduct of future clinical trials.
Methods:
Prior to commencing full-scale data collection, a feasibility study assessed 51 subjects (25 ASD, 26 TD) to ensure: standardization and viability of data collection across sites; valid and reliable implementation of experimental measures; effectiveness of data processing, extraction, and quality control procedures; and reliability of data management, upload, and sharing systems. The main study commenced in October 2016 and will include 200 rigorously characterized children with ASD (6-11 years; IQ 60-150) and 75 typically developing (TD) control subjects at three time points (Baseline, 6 weeks, 24 weeks). Detailed manuals of procedures (MOPs) and identical biomarker acquisition hardware and software are intended to minimize variance in ascertainment across sites, and clinical characterization is standardized with a clinical MOP and regular teleconferences to ensure reliability. A unique study governance brings together diverse expertise to facilitate progress from discovery to biomarker qualification. To provide opportunity for confirming biomarker results in independent samples, several EEG and ET paradigms are harmonized with those utilized in EU-AIMS.
Results:
As of October 2017, 203 participants have been enrolled in the main study, with 181 having reached 6 week visits and 116 having reached 24 week visits. Data acquisition procedures have been highly successful, with valid data acquisition rates above 96% across biomarker data modalities, and longitudinal attrition has been minimal (N=15). Panels in this symposium will report data from the interim analysis sample, at which point approximately half of the main study sample will have completed a 6 week visit. Interim analyses will focus on preliminary evaluation of biomarkers for clinical trials, in terms of acquisition and psychometric properties, as well as utility for stratification, discrimination, and indicating clinical status.
Conclusions:
The ABC-CT, and other consortia like it, are advancing the goal of clinically practicable biomarkers by investigating well-evidenced biomarkers in large, well-characterized cohorts in the context of a longitudinal design. Progress in these studies is laying groundwork for more sensitive and reliable measurement in clinical trials, and the use of economical and scalable biomarker technologies holds promise for eventual deployment in a broader range of clinical and research contexts.