Cost-effectiveness of Genome and Exome Sequencing in Children Diagnosed with Autism Spectrum Disorder

Tracy Yuen, Melissa T. Carter, Peter Szatmari, Wendy J. Ungar

Genome (GS) and exome sequencing (ES) could potentially identify pathogenic variants with greater sensitivity than chromosomal microarray (CMA) in autism spectrum disorder (ASD) but are costlier and result interpretation can be uncertain. Study objective was to compare the costs and outcomes of four genetic testing strategies in children with ASD. A microsimulation model estimated the outcomes and costs (in societal and public payer perspectives in Ontario, Canada) of four genetic testing strategies: CMA for all, CMA for all followed by ES for those with negative CMA and syndromic features (CMA+ES), ES or GS for all. Compared to CMA, the incremental cost-effectiveness ratio (ICER) per additional child identified with rare pathogenic variants within 18 months of ASD diagnosis was $CAN5997.8 for CMA+ES, $CAN13,504.2 for ES and $CAN10,784.5 for GS in the societal perspective. ICERs were sensitive to changes in ES or GS diagnostic yields, wait times for test results or pre-test genetic counselling, but were robust to changes in the ES or GS costs. Strategic integration of ES into ASD care could be a cost-effective strategy. Long wait times for genetic services and uncertain utility, both clinical and personal, of sequencing results could limit broader clinical implementation.