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

Abstract

PurposeThe purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers.MethodsRapid 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.ResultsOf 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.ConclusionRapid 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.GENETICS in MEDICINE advance online publication, 15 March 2018; doi:10.1038/gim.2018.37.

Translating genomic testing results for pediatric critical care: Opportunities for genetic counselors

“…Previous studies have assessed the technical aspects of integrating genetic sequencing to critical care settings such as turn-around times, cost effectiveness, and medical actionability of results (Clark et al, 2019;Kapil et al, 2019;Stark et al, 2018). They have looked at parental experiences with GS in NICU settings and have stressed the need for genetic counseling for families considering such testing (Ayres, Gallacher, Stark, & Brett, 2019).…”

Genetic counseling in pediatric acute care: Reflections on ultra‐rapid genomic diagnoses in neonates

“…These factors can contribute to cognitive disorganization and inhibit parents' ability to process complex medical information, and therefore to make informed, autonomous decisions regarding their infant's healthcare (McCarthy Veach, LeRoy, & Bartels, 2003;Woolley, 1990). Obtaining a diagnosis in a critically unwell infant may guide management, treatment, or decision-making around palliative care (Meng et al, 2017;Mestek-Boukhibar et al, 2018;Petrikin et al, 2015;Stark, Lunke, et al, Stark, Lunke, et al, 2018;van Diemen et al, 2017;Willig et al, 2015). Additionally, genomic sequencing has the potential to diagnose ultra-rare conditions (Friedman et al, 2018;Wright et al, 2018), which we define as conditions for which there are two or fewer relevant publications in the scientific literature and therefore limited information regarding natural history.…”

Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience

“…NGS‐based testing reduces time, cost, and invasive testing compared to the traditional diagnostic work‐up . We and others recommend a “sequence early” approach, as rapid diagnosis offers the greatest opportunity to influence patient outcomes …”

“…21,32 We and others recommend a "sequence early" approach, as rapid diagnosis offers the greatest opportunity to influence patient outcomes. 32,33 The diagnostic success of NGS is linked to the cohort inclusion criteria stringency; lower stringency leads to lower diagnostic success. 19 We did not implement strict inclusion criteria.…”