OBJECTIVES: In the United States, there is an increasing demand for evidence to support the adoption and use of rapid whole genome sequencing(rWGS) by rigorously demonstrating its real-world value. We aimed to assess the cost-effectiveness of rWGS in critically ill pediatric patients with diseases of unknown cause.

METHODS: Data were collected prospectively of patients admitted to the Nicklaus Children’s Hospital’s intensive care units from March 2018 to September 2020, with rWGS (N=65). Patients were nominated for the study by a clinical team of cardiologists, neonatologists, critical care pediatricians, neurologists, and geneticists and were included in the study if they exhibited an undiagnosed, complex, and potentially genetic abnormality, not specific to an apparent genetic syndrome that could be diagnosed or confirmed using a traditional diagnostic investigation. As a comparator, a retrospective cohort of pediatric critically ill patients who underwent standard diagnostic genetic testing and met the inclusion criteria was ascertained from an electronic medical record review of all patients who received a clinical genetics assessment at the Nicklaus Children Hospital during the same time frame as the rWGS group (N=305). We determined total costs, length of diagnostic odyssey(LODO), diagnostic yield (DY), and incremental cost-effectiveness ratio using doubly robust estimators. Sensitivity analyses explored the robustness of ICER through bootstrapping, with cost-effectiveness acceptability curves produced from such bootstraps.

RESULTS: The LODO was significantly lower in the rWGS than the standard diagnostic genetic testing group (median 29 vs. 184 days respectively, p<0.001). rWGS resulted in a diagnosis in 39.8% while standard testing in 13.5% (p = 0.026). rWGS dominated the standard diagnostic genetic testing and resulted in a mean saving per person of $100,440 (SE=26,497, p<0.001) and a total of $6.53M for 65 patients.

CONCLUSIONS: rWGS in critically ill pediatric patients is cost-effective, cost-saving, shortens diagnostic odyssey, and triples the DY of traditional approaches.