OBJECTIVES: Severe, neonatal onset mitochondrial disorders (MitD) are difficult to diagnose and cause substantial strain on patients and caregivers. This study explores the value of Early Whole Exome Sequencing (eWES), an expensive, last-line diagnostic, relative to the current standard of care (SOC) for the diagnosis of newborns suspected of having a severe MitD.

METHODS: We conducted a cost-effectiveness analysis from the US societal perspective, using a hybrid decision tree Markov model, over a 25-year time horizon and an annual 3% discount rate. Parameters were populated using published literature values of comparable disease states, expert opinion and the Pediatric Health Information System database, which collects inpatient encounter data from 47 U.S. children’s hospitals. Incremental cost-effectiveness ratios and incremental net monetary benefits (iNMB) were calculated relative to the SOC. One-way sensitivity analyses, probabilistic sensitivity analyses (PSA) and cost-effectiveness acceptability curves were also generated.

RESULTS: INMBs of eWES relative to SOC at a willingness to pay (WTP) of $50,000 and $200,000 per quality-adjusted life year for the base case were $24,888 and $25,200, respectively. eWES, SOC diagnostic probabilities and neonatal intensive care unit length of stay were revealed as important parameters driving base case results. PSA revealed that eWES had a 68% likelihood of being cost-effective at a WTP of $50,000, a 74% likelihood of being cost-effective at $200,000 and 66% likelihood of being cost-effective at $0.

CONCLUSIONS: EWES dominates SOC in diagnosing patients suspected of having a MitD. As the WTP threshold increases, eWES increasingly becomes more likely to be cost-effective relative to SOC, indicating that the mechanism of cost-effectiveness is cost-minimization. Our findings demonstrate this current wave of innovative sequencing is a cost-effective measure for diagnosing severe MitD in select neonates, while also highlighting future research necessary to determine the value of genetic diagnostics for MitD neonates.