Early genomic sequencing increases diagnostic yield and is cost effective in children.

Aim: To evaluate the cost-effectiveness of exome sequencing (ES) in patients with suspected genetic kidney disease (GKD) compared with current standard diagnostic care, and to evaluate the optimal timing of ES. Background(s): There is an urgent need to determine the health economic value of genomic testing in kidney disease patients. Method(s): This model based economic analysis was informed by a pragmatic, multicentre study which included 87 patients with suspected monogenic glomerular disease. Resource use for non-genomic investigations were also informed by data from the cohort, in addition to current guidelines. Six diagnostic strategies reflecting current practice were compared. Result(s): ES achieved a diagnosis in 23/63 (36.5%) adults and 10/24 (41.6%) children. The average cost of ES (including sequencing, analysis, and related consultations) was $2,355 in both children and adults. Children: Standard investigations were estimated to diagnose 4.0%, with an average estimated cost of $6,119 per child. Integrating ES as a first line test was cost saving, with an incremental cost saving per additional diagnosis of $3,230 compared to standard diagnostic care. Adults: Standard investigations were estimated to diagnose 7.9%, with an average estimated cost of $1,834 per adult, (including a biopsy rate of 70%). Integrating ES early resulted in an incremental cost per additional diagnosis of $5,456 relative to standard care. Conclusion(s): Integrating ES early in the diagnostic pathway is likely to be more effective and less costly for establishing a diagnosis and informing care in children. In adults, the incremental cost per additional diagnosis may be justified, depending on the value of a genomic diagnosis. Applying ES as a last resort test resulted in considerably higher cost compared with earlier application in the diagnostic trajectory.