Authors' objectives: The objectives of this study were to: (1) estimate the precise cost per trio for both GS and ES using a bottom-up micro-costing approach for a targeted patient population consisting of mostly children with suspected rare genetic conditions and their biological parents and (2) using data from a randomized controlled trial , conduct a cost-consequence analysis (CCA) to estimate the incremental cost of trio GS vs. trio ES per unit improvement in molecular diagnostic yield from an institutional payer perspective.

Authors' results and conclusions: This study furnished evidence of the cost and cost-effectiveness of trio GS vs. ES using a bottom-up micro-costing approach. GS was associated with higher costs and a similar diagnostic yield for this randomized population with RDs.

Authors' recommendations: The study provides comprehensive costs for future economic evaluations of alternative diagnostic pathways to inform future funding and implementation decisions and impetus for further evaluating variants uniquely detectable by GS.

Authors' methods: The study assessed cost per trio for GS and for ES (Illumina NovaSeq 6000) excluding mark-ups, fees, and charges. The estimation was conducted using a bottom-up micro-costing approach based on the laboratory workflow and the volumes for sequencing-related inputs provided by the Department of Paediatric Laboratory Medicine at SickKids. The total cost was decomposed into seven categories, including reagents, consumables, small and large equipment, shipping and ordering, software, labour and overhead. The analysis was conducted from an institutional payer perspective based on the harmonized diagnostic laboratory practices at SickKids and CHEO. The aggregated cost per trio for GS and ES were determined and the total program costs were estimated for each enrollment year. To address parameter uncertainty in the model, a probabilistic analysis using Monte Carlo simulations was performed. A CCA was conducted to examine the incremental cost and incremental diagnostic yield of GS vs. ES.

Authors' identified further research: Genome-wide sequencing (GWS) is a powerful but resource-intensive diagnostic tool that enhances the identification of genetic variants associated with disease risk. In addition to detecting variants directly related to the primary clinical indication, GWS can identify secondary findings in genes such as BRCA1 and BRCA2, where early intervention may improve health outcomes. However, the expanding scope of secondary findings increases demand for surveillance and management across multiple specialties, straining healthcare resources and budgets. The classification of secondary finding testing as an opportunistic screening measure remains subject to debate due to uncertainties regarding its clinical utility and cost-effectiveness. Research on GWS secondary findings provides an opportunity to evaluate the incremental cost-effectiveness of secondary finding ascertainment among families of children with unexplained suspected genetic conditions. Participants undergoing trio genome or exome sequencing will be matched (1:2) based on age group, primary result type, and clinical indication, over a two-year study period. Health service utilization data will be collected from both the child and one adult family member at six-month intervals. The total cost per child and per family unit will be determined by multiplying resource utilization by corresponding unit costs, with calculations performed from both public payer and societal perspectives. Mean costs for secondary finding–positive and secondary finding–negative groups will be statistically compared, with adjustments for demographic differences as necessary. The incremental cost-effectiveness ratio will be derived from the difference in mean cost relative to secondary finding yield, while clinical utility will be assessed through changes in patient management and the Clinician-Reported Genetic Testing Utility Index (C-GUIDE) score. Sensitivity analyses will assess the robustness of findings under varying cost and effectiveness assumptions. The findings of this study will provide critical evidence to inform government policy, funding allocation, and clinical guidelines regarding secondary finding testing in GWS. The inclusion of family perspectives and the application of a novel clinical utility measure represent significant advancements in the economic evaluation of genomic medicine, with potential implications for long-term healthcare planning and resource allocation.

Project Status: Completed

URL for project: https://gsontario.ca/what-is-gso/

URL for protocol: https://www.cmajopen.ca/content/10/2/E460.short

Year Published: 2025

URL for published report: https://lab.research.sickkids.ca/task/wp-content/uploads/sites/66/2025/05/FULL-REPORT-1.pdf

Requestor: Government agencies, health ministries or public health organizations, insurance companies or payers, hospital decision-makers or healthcare administrators, regulatory agencies, pharmaceutical or medical device companies

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Organisation Name: Technology Assessment at SickKids

Contact Address: Program of Child Health Evaluative Sciences, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8 tel: (416) 813-8519 fax: (416) 813-5979

Contact Name: wendy.ungar@sickkids.ca

Contact Email: wendy.ungar@sickkids.ca

Copyright: <p>Technology Assessment Unit of the Hospital for Sick Children (TASK)</p>