학술논문

An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm
Document Type
article
Source
American Journal of Human Genetics. 107(5)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Health Sciences
Genetics
Clinical Trials and Supportive Activities
Clinical Research
Biotechnology
Infectious Diseases
Pediatric
Human Genome
Good Health and Well Being
Chromosome Mapping
Clinical Decision-Making
Critical Illness
Disease Management
Female
Genetic Diseases
Inborn
Genetic Testing
Genome
Human
Humans
Infant
Infant
Newborn
Intensive Care Units
Neonatal
Logistic Models
Male
Prospective Studies
Time Factors
Whole Genome Sequencing
RCIGM Investigators
NSIGHT2
clinical utility
diagnostic testing outcomes
healthcare cost-benefit analysis
neonatal intensive care unit
pediatric intensive care unit
rapid whole-exome sequencing
rapid whole-genome sequencing
ultra-rapid whole-genome sequencing
Medical and Health Sciences
Genetics & Heredity
Biological sciences
Biomedical and clinical sciences
Health sciences
Language
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.