Genet Med. 2025 Aug 21:101561. doi: 10.1016/j.gim.2025.101561. Online ahead of print.
ABSTRACT
PURPOSE: Diagnosing rare diseases is costly. The objectives were to microcost exome (ES) and genome sequencing (GS) trios and estimate the incremental costs of GS per additional diagnosis from an institutional payer perspective.
METHODS: Trios (proband plus biological parents) referred for sequencing were randomly assigned to ES or GS. Laboratory workflow and sequencing were microcosted. Total and category cost per trio were estimated probabilistically. Effectiveness was expressed as diagnostic yield (rates of diagnostic or partially diagnostic variants detected). Incremental costs and effectiveness were calculated.
RESULTS: The mean total cost per trio was CAD 2888.79 (95% CI 2567.72, 3492.72) for ES (n=329) and 4364.02 (95% CI 3984.94, 5013.67) for GS (n=324). Reagents accounted for 34% and 61% of total costs for ES and GS, respectively. The incremental cost of GS was 1475.23. The diagnostic yield was 35.9% for ES and 32.7% for GS with a difference of 0.032 (95% CI: -0.041, 0.104, p-value 0.397).
CONCLUSION: GS demonstrated higher costs and a similar diagnostic yield to ES but was limited by technical capabilities at the time of the study. The study provides comprehensive costs for economic evaluation comparing of alternative diagnostic pathways and impetus for further evaluating variants uniquely detectable by GS.
PMID:40852796 | DOI:10.1016/j.gim.2025.101561
