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
Author
Dimmock, David P; Clark, Michelle M; Gaughran, Mary; Cakici, Julie A; Caylor, Sara A; Clarke, Christina; Feddock, Michele; Chowdhury, Shimul; Salz, Lisa; Cheung, Cynthia; Bird, Lynne M; Hobbs, Charlotte; Wigby, Kristen; Farnaes, Lauge; Bloss, Cinnamon S; Kingsmore, Stephen F; Investigators, the RCIGM; Bainbridge, Matthew N; Barea, Jaime; Batalov, Sergey; Bezares, Zaira; Braun, Joshua JA; Del Campo, Miguel; Carroll, Jeanne; Cohenmeyer, Casey; Coufal, Nicole G; Diaz, Carlos; Ding, Yan; Ellsworth, Katarzyna; Evans, Marva; Feigenbaum, Annette; Friedman, Jennifer; Gleeson, Joe; Hansen, Christian; Honold, Jose; James, Kiely; Jones, Marilyn C; Kimball, Amy; Knight, Gail; Van Der Kraan, Lucitia; Lane, Brian; Le, Jennie; Leibel, Sandra; Lenberg, Jerica; Mashburn, Dana; Moyer, Laurel; Mulrooney, Patrick; Nahas, Shareef; Oh, Daeheon; Orendain, Daniken; Oriol, Albert; Ortiz-Arechiga, Maria; Prince, Lance; Rego, Seema; Reyes, Iris; Sanford, Erica; Sauer, Charles; Schwanemann, Leila; Speziale, Mark; Suttner, Denise; Sweeney, Nathaly; Song, Richard; Tokita, Mari; Veeraraghavan, Narayanan; Watkins, Kelly; Wong, Terence; Wright, Meredith S; Yamada, Catherine
Source
American Journal of Human Genetics. 107(5)
Subject
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.