The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials.
Autism spectrum disorder
Biological motion
Biomarkers
Eye tracking
Face processing
Gaze pattern
Visual attention
Journal
Molecular autism
ISSN: 2040-2392
Titre abrégé: Mol Autism
Pays: England
ID NLM: 101534222
Informations de publication
Date de publication:
21 03 2022
21 03 2022
Historique:
received:
05
07
2021
accepted:
20
12
2021
entrez:
22
3
2022
pubmed:
23
3
2022
medline:
28
4
2022
Statut:
epublish
Résumé
Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA's Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.
Sections du résumé
BACKGROUND
Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD).
METHODS
The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications.
RESULTS
All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills.
LIMITATIONS
No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts.
CONCLUSIONS
All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA's Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.
Identifiants
pubmed: 35313957
doi: 10.1186/s13229-021-00482-2
pii: 10.1186/s13229-021-00482-2
pmc: PMC10124777
doi:
Substances chimiques
Biomarkers
0
Banques de données
ClinicalTrials.gov
['NCT02996669']
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
15Subventions
Organisme : NIMH NIH HHS
ID : K01 MH104739
Pays : United States
Organisme : FDA HHS
ID : U01 FD007000
Pays : United States
Organisme : NIMH NIH HHS
ID : U19 MH108206
Pays : United States
Informations de copyright
© 2022. The Author(s).
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