Rapid Genome Sequencing Compared to a Gene Panel in Critically Ill Infants with a Suspected Genetic Disorder: An Economic Evaluation

Introduction Rapid genome sequencing (rGS) provides high diagnostic yield for critically ill infants with suspected genetic disorders, but has high upfront costs and insufficient insurance coverage. Assessing the downstream costs and health outcomes associated with rGS is important for guiding coverage decisions. This study compares 1-year healthcare costs and quality-adjusted life years (QALYs) for: 1) early rGS (within 7 days of admission) for all infants, and 2) early targeted neonatal gene sequencing (NewbornDx) for all infants, followed by later rGS (after 7 days) for undiagnosed infants. Study Design The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a multicenter, prospective study that enrolled 400 hospitalized infants under one year of age with suspected genetic disorders. All participants underwent both rGS and NewbornDx. Using GEMINI data and 2023 Medicare rates, we developed a decision tree to compare total costs and QALYs over a 1-year period for the two testing strategies. Results The diagnostic yield and upfront testing costs were higher for rGS (49%; $12,297) than NewbornDx (27%; $2,449; p<0.05). As neither early testing nor diagnosis significantly affected QALYs, we conducted a cost-minimization analysis, focusing solely on cost differences between strategies. Over one year, early rGS was estimated to save $158,592 per patient (95% CI: $63,701-$253,292) compared to early NewbornDx with later rGS if necessary. Conclusions Early rGS results in substantial healthcare cost savings, highlighting the need to expand reimbursement to improve access early in a hospitalization for critically ill infants.