An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm
An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm
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DOI：
10.1016/j.ajhg.2020.10.003
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发表时间：
2020-11-05
影响因子：
9.8
通讯作者：
Kingsmore, Stephen F.
中科院分区：
文献类型：
--
作者：
Dimmock, David P.;Clark, Michelle M.;Kingsmore, Stephen F.
第二项《基因组医学与公共卫生新生儿测序》(NSIGHT2)研究是一项对重症监护病房(ICU)中病因不明的婴儿进行快速全基因组测序(RWGS)或快速全外显子组测序(RWES)的随机对照试验。重症婴儿没有被随机分组，并接受了超快速全基因组测序(UrWGS)。在此，我们报告了临床医生对快速基因组测序(RGS)临床应用的调查结果。201名婴儿中有154名(77%)达到了主要终点--临床医生认为RGS是有用的--。阳性和阴性试验均被评为具有临床实用价值(分别为45例中的42例[93%]和156例中的112例[72%])。医生报告说，RGS改变了57名(28%)婴儿的临床管理，特别是那些接受urWGS(p=0.0001)和阳性测试(p<；0.00001)的婴儿。32名婴儿(15%)的结局被RGS感知到改变。阳性测试比阴性测试更频繁地改变结果(p<；0.00001)。在Logistic回归模型中，当管理层发生变化时，RGS被视为有用的可能性增加了6.7倍(95%可信区间1.8-43.3)。当结果为阳性(95%CI 4.7-22.4)且周转时间较短(优势比0.92，95%CI 0.85-0.99)时，管理层发生变化的可能性是对照组的10.1倍。RGS很少在家庭中引起临床医生感知的困惑或痛苦(6/207[3%])。总之，临床医生认为ICU中病因不明的婴儿的第一级RGS具有很高的临床实用性和较低的伤害可能性。无论结果是积极的还是消极的，RGS都被认为是有益的。
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.