An RCT of Rapid Genomic Sequencing Among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2020 Nov 6

PMID 33157007

Citations 77

Authors

David P Dimmock

Michelle M Clark

Mary Gaughran

Julie A Cakici

Sara A Caylor

Christina Clarke

Michele Feddock

Shimul Chowdhury

Lisa Salz

Cynthia Cheung

Lynne M Bird

Charlotte Hobbs

Kristen Wigby

Lauge Farnaes

Cinnamon S Bloss

Stephen F Kingsmore

Affiliations

Soon will be listed here.

Abstract

The second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2) study was a randomized, controlled trial of rapid whole-genome sequencing (rWGS) or rapid whole-exome sequencing (rWES) in infants with diseases of unknown etiology in intensive care units (ICUs). Gravely ill infants were not randomized and received ultra-rapid whole-genome sequencing (urWGS). Herein we report results of clinician surveys of the clinical utility of rapid genomic sequencing (RGS). The primary end-point-clinician perception that RGS was useful- was met for 154 (77%) of 201 infants. Both positive and negative tests were rated as having clinical utility (42 of 45 [93%] and 112 of 156 [72%], respectively). Physicians reported that RGS changed clinical management in 57 (28%) infants, particularly in those receiving urWGS (p = 0.0001) and positive tests (p < 0.00001). Outcomes of 32 (15%) infants were perceived to be changed by RGS. Positive tests changed outcomes more frequently than negative tests (p < 0.00001). In logistic regression models, the likelihood that RGS was perceived as useful increased 6.7-fold when associated with changes in management (95% CI 1.8-43.3). Changes in management were 10.1-fold more likely when results were positive (95% CI 4.7-22.4) and turnaround time was shorter (odds ratio 0.92, 95% CI 0.85-0.99). RGS seldom led to clinician-perceived confusion or distress among families (6 of 207 [3%]). In summary, clinicians perceived high clinical utility and low likelihood of harm with first-tier RGS of infants in ICUs with diseases of unknown etiology. RGS was perceived as beneficial irrespective of whether results were positive or negative.

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