Validation of Indiana's Early Evaluation Hub System (EAER21)

Validation of Indiana's Early Neurodevelopmental Evaluation Hub Program

The investigators' objective is to test an innovative method of autism diagnosis that integrates clinical evaluation and assessment of biobehavioral markers in a large high-risk community-referral sample of children in the primary care setting.

Study Overview

• Status: Completed
• Conditions: Autism
• Intervention / Treatment: Diagnostic test: Eyelink Portable Duo; Diagnostic test: Integrated PCP Diagnosis and Eye-tracking Biomarker

Detailed Description

Determine whether eye-tracking biomarkers can reliably differentiate young children with and without autism in a community referred sample. The study will use a non-invasive remote eye-tracking system (Eyelink Portable Duo) to acquire a short series (less than 15 mins) of eye-tracking measures (e.g., looking time, pupil diameter, oculomotor dynamics), which may be associated with autism in young children. Differences in metrics between children with and without autism will be compared to validate potential eye-tracking biomarkers.

Determine whether a combination of clinical (i.e., EE Hub PCP measures) and eye-tracking biomarkers can be used to accurately predict autism diagnostic outcome in a sample of young children evaluated for autism in the primary care setting.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Health Network
    • Batesville, Indiana, United States, 47006
      • Margaret Mary Health Pediatrics
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
    • Muncie, Indiana, United States, 47304
      • Meridian Health Pediatrics
    • Newburgh, Indiana, United States, 47630
      • Deaconess Riley Children's Specialty Center
    • South Bend, Indiana, United States, 46617
      • Primary Care Partners of South Bend
    • Warsaw, Indiana, United States, 46580
      • Lutheran Health Physicians Pediatric Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Young children ages 14-48 months seen at an EE hub and referred for a comprehensive autism evaluation.

Children must have English-speaking caregivers. Children must have a legal guardian that is able to provide consent.

Exclusion Criteria:

Child is younger than 14 months or older than 48 months. Child's caregiver(s) is/are not English-speaking.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Children Undergoing Developmental Evaluation; Participating EE Hubs referred a prospective, consecutive sample of children who received an EE Hub evaluation. Next, the study team traveled to the EE Hub to conduct a follow-up gold-standard autism diagnostic assessment (reference standard diagnosis) and eye-tracking biomarker battery (index test; Aim 2) within 16 weeks of EE Hub evaluation. Reference standard diagnosis was made by a licensed clinical psychologist with expertise in autism diagnosis based upon a research evaluation including the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), Vineland Adaptive Behaviors Scale, Third Edition (VABS-3), Mullen Scales of Early Learning (MSEL), and a caregiver interview to assess for DSM-5 autism criteria. Children also completed a short (< 15min) eye-tracking activity where the children view a series of different images/videos while the children's eye movements and pupil diameter was measured.

Diagnostic test: Eyelink Portable Duo; Eye-tracking data will be collected using a commercially-available remote eye-tracking system (Eyelink Portable Duo). Eye movements and pupil diameter will be collected while participants view a series of developmentally appropriate pictures and movies. The eye-tracker consists of two cameras; one that monitors eye movements and a second scene camera that monitors head movements, which permits eye tracking to take place without any equipment touching the child. Children will be asked to sit in highchair or on a caregiver's lap and will face a computer monitor. After a sticker is applied to the child's forehead and brief eye-movement calibration completed, next visual stimuli (i.e., pictures and videos) will be presented on a laptop computer monitor that is placed at approximately 60-80cm from the child. The eye tracking portion of the visit will last approximately 15 minutes or until the child is no longer able to attend to pictures/videos.; Diagnostic test: Integrated PCP Diagnosis and Eye-tracking Biomarker; A Classification and Regression Tree (CART) Analysis, based on recursive partitioning, was used to determine which combination of variables (EE Hub PCP diagnosis, diagnostic certainty, composite biomarker, and biomarker frequency [sum of all individual biomarkers (0-6) that exceeded the 95% specificity threshold for each child]) best predicted reference standard autism diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist	Sensitivity and specificity of a composite eye-tracking (i.e., index) test, which was a consolidated measure based on significant eye-tracking indices, compared to reference standard expert clinical autism diagnosis.	Day 1
Agreement Between Integrated PCP, Eye-tracking Biomarker Score and Expert Autism-specialist	Classification and Regression Tree (CART) analysis, based on recursive partitioning, is used to determine which combination of variables (EE Hub PCP diagnosis, diagnostic certainty, composite biomarker, and biomarker frequency [sum of all individual biomarkers (0-6) that exceeded the 95% specificity threshold for each child]) best predicted reference standard autism diagnosis.	Day 1

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute of Mental Health (NIMH); Purdue University
• Investigators: Principal Investigator: Rebecca McNally-Keehn, PhD, HSPP, IU School of Medicine; Principal Investigator: Brandon Keehn, PhD, Purdue University

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2019
• Primary Completion (Actual): September 23, 2022
• Study Completion (Actual): September 23, 2022

Study Registration Dates

• First Submitted: September 4, 2024
• First Submitted That Met QC Criteria: September 4, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: biomarkers; primary care; diagnosis; eye-tracking
• Other Study ID Numbers: 1806262614; R21MH121747 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data from this study is submitted to the National Institute of Mental Health Data Archive (NDA). NDA is a data repository run by the National Institute of Mental Health (NIMH) that allows researchers studying autism and other conditions to collect and share deidentified information with each other. A data repository is a large database where information from many studies is stored and managed.

During and after the study, the researchers will send deidentified information to NDA. Other researchers nationwide can then file an application with the NIMH to obtain access deidentified study data for research purposes.

• IPD Sharing Time Frame: Investigators will follow NIMH NDAR policies for submission of data.
• IPD Sharing Access Criteria: Investigators will follow NIMH NDAR policies for submission of data. Other researchers nationwide can file an application with the NIMH to obtain access deidentified study data for research purposes.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No