Cost-effectiveness of Genome and Exome Sequencing in Children Diagnosed with Autism Spectrum Disorder
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.
The authors would like to acknowledge inputs from Robyn Hayeems, Ny Hoang, Cheryl Shuman and Kate Tsiplova on the parameters used in the model.
All authors (TY, MTC, PS, WJU) contributed to the conceptualization of model, interpretation of findings, editing of the manuscript and provided final approval of the paper. TY and WJU were responsible for model building, data analysis and drafting the manuscript.
Compliance with Ethical Standards
TY was supported through the Canada Institutes of Health Research Autism Research Training Program, Doctoral Autism Scholars Award, Ontario Graduate Scholarship and RestraComp Hospital for Sick Children Foundation Student Scholarship Program. No other funding was received for this study.
Conflict of interest
All authors (TY, MTC, PS, WJU) declare no conflicts of interest.
Human and animal rights statement
This article does not contain studies with human participant or animals performed by any of the authors.
For this type of study formal consent is not required.
- 1.Centers for Disease Control and Prevention. Prevalence and characteristics of autism spectrum disorder among children aged 8 years- Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States. Morb Mortal Wkly Rep. 2012;2016:65.Google Scholar
- 10.Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;19:249–55.CrossRefPubMedGoogle Scholar
- 22.Statistics Canada. Table 282-0074. Labour force survey estimates (LFS), wages of employees by job permanence, union coverage, sex and age group [Internet]. 2015 [cited 2016 Jan 19]. http://www5.statcan.gc.ca/cansim/a26?lang=eng&id=2820074. Accessed Jan 2016.
- 23.Software TreeAge. TreeAge Pro 2015. Williamstown: TreeAge Software; 2015.Google Scholar
- 24.Rossi M, El-Khechen D, Black MH, Farwell Hagman KD, Tang S, Powis Z. Outcomes of diagnostic exome sequencing in patients with diagnosed or suspected autism spectrum disorders. Pediatr Neurol. 2017;70(34–43):e2.Google Scholar
- 28.Health Quality Ontario. Ontario Genetic Advisory Committee terms of reference [Internet]. Health Quality Ontario; 2016. http://www.hqontario.ca/portals/0/documents/evidence/reports/ogac-terms-of-reference-en.pdf. Accessed May 2017.
- 42.Ontario Genetics Secretariat. Clinical genetics wait time study report. Toronto: Hospital for Sick Children; 2014.Google Scholar
- 45.Hospital for Sick Children. Molecular genetic lab- Billing and CPT codes. Toronto: Hospital for Sick Children; 2015.Google Scholar
- 46.Ministry of Health and Long-Term Care. Schedule of benefits for physician services under the Health Insurance Act [Internet]. 2015 [cited 2015 Nov 9]. http://www.health.gov.on.ca/english/providers/program/ohip/sob/physserv/physserv_mn.html. Accessed Nov 2015.
- 47.Régie de l’assurance maladie du Québec. Manuel de facturation. rémunération à l’acte. Table B-Tarification des visites. [Internet]. Régle de l’assurance maladie Quebec; 2015 [cited 2016 Apr 25]. http://www.ramq.gouv.qc.ca/fr/professionnels/medecins-specialistes/manuels/Pages/facturation.aspx. Accessed April 2016.