Autism
Conditions
Keywords
primary care, biomarkers, eye-tracking, diagnosis
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTEyelink 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_TESTIntegrated 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.
Sponsors
Purdue University
National Institute of Mental Health (NIMH)
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Months to 48 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist | Day 1 | 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. |
| Agreement Between Integrated PCP, Eye-tracking Biomarker Score and Expert Autism-specialist | Day 1 | 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. |
Countries
United States
Participant flow
Recruitment details
Seven EE Hubs set within primary care practices referred children, ages 14-48 months evaluated for autism in the community primary care setting, to the study between June 2019 and August 2022. To be included, children were age 14-48 months at time of EE Hub evaluation and had an English-speaking primary caregiver/guardian. Participating EE Hubs referred a prospective, consecutive sample of children who received an EE Hub evaluation.
Participants by arm
| Arm | Count |
|---|---|
| Children Undergoing Developmental Evaluation Participating EE Hubs referred a prospective, consecutive sample of children who received an 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.
Eyelink Portable Duo: Eye movements and pupil diameter will be collected while participants view a series of developmentally appropriate pictures and movies. Children will be asked to sit in highchair or on a caregiver's lap and will face a computer monitor. 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.
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. | 146 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Eye-tracking calibration / validation could not be completed with eight children | 8 |
Baseline characteristics
| Characteristic | Children Undergoing Developmental Evaluation |
|---|---|
| Age, Continuous | 2.55 years STANDARD_DEVIATION 0.6 |
| Composite Eye-tracking Biomarker | 89 Participants |
| Race/Ethnicity, Customized Race / ethnicity Asian | 2 Participants |
| Race/Ethnicity, Customized Race / ethnicity Black | 14 Participants |
| Race/Ethnicity, Customized Race / ethnicity Latine, any race | 21 Participants |
| Race/Ethnicity, Customized Race / ethnicity More than one race | 6 Participants |
| Race/Ethnicity, Customized Race / ethnicity Non-Latine White | 96 Participants |
| Race/Ethnicity, Customized Race / ethnicity Unspecified or not reported | 7 Participants |
| Region of Enrollment United States | 146 participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 154 |
| other Total, other adverse events | 0 / 154 |
| serious Total, serious adverse events | 0 / 154 |
Outcome results
Primary
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.
Time frame: Day 1
Population: The number of participants analyzed does not differ from the number of participants assigned to this arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Autism (Reference Standard) | Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist | Autism (index test) | 79 Participants |
| Autism (Reference Standard) | Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist | Non-autism (index test) | 23 Participants |
| Non-Autism (Reference Standard) | Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist | Autism (index test) | 10 Participants |
| Non-Autism (Reference Standard) | Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist | Non-autism (index test) | 34 Participants |
Primary
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.
Time frame: Day 1
Population: Because the goal of tiered diagnostic models, such as the EAE Hub system, is that PCPs can rule in/out autism in a subset of children and refer more complicated cases to a specialist, terminal nodes for the CART analysis were identified as autism, non-autism, or refer. As such, the number of participants analyzed differs from the number of participants assigned to the arm. A total of 19 children were classified as refer, and thus the total number of participants was 127.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Autism (Reference Standard) | Agreement Between Integrated PCP, Eye-tracking Biomarker Score and Expert Autism-specialist | Non-Autism (index text) | 9 Participants |
| Autism (Reference Standard) | Agreement Between Integrated PCP, Eye-tracking Biomarker Score and Expert Autism-specialist | Autism (index text) | 88 Participants |
| Non-Autism (Reference Standard) | Agreement Between Integrated PCP, Eye-tracking Biomarker Score and Expert Autism-specialist | Non-Autism (index text) | 26 Participants |
| Non-Autism (Reference Standard) | Agreement Between Integrated PCP, Eye-tracking Biomarker Score and Expert Autism-specialist | Autism (index text) | 4 Participants |