Biomarkers Consortium - The Autism Biomarkers Consortium for Clinical Trials (ABC-CT)

Establishing biomarkers to improve treatments for children with autism spectrum disorders

The Problem
Interventions for social impairments in children with autism are complicated by the heterogeneity of the disease and hampered by the lack of objective measures of change in social functioning.
The Solution
This program has met its goal to establish biomarkers that can be used as biomarkers in autism. Its EEG measure was the first psychiatric biomarker ever accepted in the history of FDA’s Biomarker Qualification Program.

Overview

Autism Spectrum Disorders (ASDs), which affect an estimated one percent of children worldwide, are a group of developmental disorders characterized by impairments in reciprocal social interaction, as well as by the presence of stereotyped or repetitive behavior, interests, or activities. ASD affects early brain development with signs and symptoms of autism emerging in the first 2 years of life. ASD’s underlying pathologies remain unknown, and diagnosis is complicated by ASD’s varied and wide ranging clinical presentations (heterogeneity), including cognitive function from severely impaired to above average. This heterogeneity and the lack of any objective, quantifiable measures of change in social functioning have hindered attempts to develop interventions for the core social impairments of autism. Therefore the need is urgent for biomarkers that can separate subjects into more homogeneous subgroups characterized by common pathophysiology, which will maximize the ability of clinical trials to detect benefit, as well as for biomarkers that are sensitive to change in social functioning, which may ultimately serve as robust predictors of treatment effects or facilitate choice of treatments for individual patients.

To address this need for biomarkers, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) project is evaluating the potential utility of various ASD biomarkers, including EEG to measure brain function, eye tracking technology to measure visual attention and automated recording techniques to assess behavior and speech, in children aged 6 to 11 years across a 6-month period. In particular, the project will compare lab-based measures to clinician and caregiver assessments of social impairment domains, to determine the measures most sensitive to indicators of clinical status. This project will also evaluate whether a select set of eye tracking and EEG measures, individually or in combination, could serve as stratification biomarkers, or as sensitive and reliable measures of change, in clinical trials. Finally, the project will collect blood-based DNA samples from all trial participants, including the parents of the persons with ASD to support future genomic and other analyses.

Partners

Public-Sector Partners

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • U.S. Food and Drug Administration (FDA)
  • National Institute of Mental Health (NIMH)
  • National Institute of Neurological Disorders and Stroke (NINDS)

Private-Sector Partners

  • European Autism Interventions – A Multicentre Study for Developing New Medications (EU-AIMS)*
  • Janssen Research & Development, LLC*
  • Simons Foundation*

Academic Partner

  • Yale University School of Medicine
  • *Provided financial or in-kind support for this project.

FNIH Contact

  • Wesley Horton, M.S., Scientific Project Manager, whorton@fnih.org

Goals

  • Qualify a set of measures that can be used as stratification biomarkers and/or sensitive and reliable objective measures of social impairment in ASD clinical trials. These measures should function as indicative markers of long-term clinical outcome.
  • Evaluate whether a set of eye tracking and EEG measures, individually or in combination, have potential utility as stratification biomarkers and/or are sensitive and reliable measures of change in clinical trials.

Results & Accomplishments

First Psychiatric Biomarker Under Consideration by FDA The ABC-CT project team has developed measures that can be used as diagnostic enrichment biomarkers to enable the identification of groups of individuals for inclusion in ASD clinical trials. The project team submitted two Letters of Intent to FDA—one for an EEG N170 measure in November 2018 and another for an eye tracking measure in September 2019. The EEG N170 was accepted into FDA's Biomarker Qualification Program in May 2019, and the eye tracking measure was accepted in March 2020. The EEG N170 measure is the first psychiatric biomarker accepted in the FDA Biomarker Qualification Program.

Read more about the FDA acceptance of the EEG N170 LOI.