Meeting the challenges of implementing rapid genomic testing in acute pediatric care

TLDR

The study aimed to implement and prospectively evaluate a rapid genomic diagnosis program at two pediatric tertiary centers. The program used rapid singleton whole‑exome sequencing in acutely ill children with suspected monogenic disorders, with laboratory and clinical barriers addressed through continuous multidisciplinary review and a whole‑of‑system rapid team approach. Among 40 patients, 52.5% received a diagnosis within a median of 16 days, 78% of inpatients received results during the first admission, 57% of diagnosed patients experienced management changes, and the program proved cost‑effective with a cost per diagnosis of AU$13,388 and estimated savings of AU$543,178.

Abstract

The purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers.Rapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed.Of 40 enrolled patients, 21 (52.5%) received a diagnosis, with median time to report of 16 days (range 9-109 days). A result was provided during the first hospital admission in 28 of 36 inpatients (78%). Clinical management changed in 12 of the 21 diagnosed patients (57%), including the provision of lifesaving treatment, avoidance of invasive biopsies, and palliative care guidance. The cost per diagnosis was AU$13,388 (US$10,453). Additional cost savings from avoidance of planned tests and procedures and reduced length of stay are estimated to be around AU$543,178 (US$424,101). The clear relative advantage of rWES, joint clinical and laboratory leadership, and the creation of a multidisciplinary "rapid team" were key to successful implementation.Rapid genomic testing in acute pediatrics is not only feasible but also cost-effective, and has high diagnostic and clinical utility. It requires a whole-of-system approach for successful implementation.