Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: Evidence from Canada

Purpose: To determine real-world diagnostic rates, cost trajectories, and cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children with developmental and/or seizure disorders in British Columbia, Canada. Methods: Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at British Columbia Children's Hospital. Results informed a state-transition Markov model examining cost-effectiveness of 3 competing diagnostic strategies: (1) SOC with last-tier access to ES, (2) streamlined ES access, and (3) first-tier GS. Results: Through SOC, 49.4% (95% CI: 40.6, 58.2) of patients were diagnosed at an average cost of C$11,683 per patient (95% CI: 9200, 14,166). Compared with SOC, earlier ES or GS access yielded similar or improved diagnostic rates and shorter times to genetic diagnosis, with 94% of simulations demonstrating cost savings for streamlined ES and 60% for first-tier GS. Net benefit from the perspective of the health care system was C$2956 (95% CI: −608, 6519) for streamlined ES compared with SOC. Conclusion: Using real-world data, we found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings compared with current practice in a Canadian health care system.