Recent Progress of Large-Scale Biomarker Consortia and Paths Forward in Autism Biomarker Development

Autism presents significant challenges for clinical research and biomarker development due to behavioral heterogeneity and reliance on clinician- and caregiver-report measures that are limited in sensitivity, objectivity, and scalability. Biomarkers offer a complementary approach by providing biologically grounded, standardized, and potentially more sensitive indicators of the autism phenotype. We outline the potential advantages of biomarkers over traditional clinical assessments, operationalize biomarkers using U.S. Food and Drug Administration/National Institutes of Health consensus frameworks, and evaluate recent progress from large-scale biomarker consortia and the remaining challenges for 2 well-developed measurement modalities: electroencephalography and eye-tracking. We summarize findings from one of these recent biomarker consortia, the Autism Biomarkers Consortium for Clinical Trials, which has established the feasibility, stability, and regulatory relevance of several candidate biomarkers. Despite meaningful advances in the reproducibility of biological factors associated with autism, clinically actionable biomarkers remain elusive. We describe potential paths forward to overcome this obstacle, including leveraging neurogenetic syndromes and genomic stratification, aligning biomarkers with biologically specified behavioral constructs, expanding measurement into motor and vestibular domains, and applying data-driven, multimodal, and digital phenotyping approaches to advance clinical trial readiness in autism.