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An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm
American Journal of Human Genetics ( IF 8.1 ) Pub Date : 2020-11-05 , DOI: 10.1016/j.ajhg.2020.10.003
David P Dimmock 1 , Michelle M Clark 1 , Mary Gaughran 1 , Julie A Cakici 2 , Sara A Caylor 1 , Christina Clarke 1 , Michele Feddock 1 , Shimul Chowdhury 1 , Lisa Salz 1 , Cynthia Cheung 3 , Lynne M Bird 4 , Charlotte Hobbs 1 , Kristen Wigby 5 , Lauge Farnaes 1 , Cinnamon S Bloss 3 , Stephen F Kingsmore 1 ,
Affiliation  

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.



中文翻译:


对重病婴儿进行快速基因组测序的随机对照试验具有较高的临床效用、管理的改变和较低的感知危害



第二项新生儿基因组医学和公共卫生测序 (NSIGHT2) 研究是一项随机对照试验,对重症监护病房患有不明病因疾病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)。重症监护室)。重症婴儿没有被随机分组​​并接受超快速全基因组测序(urWGS)。在此,我们报告临床医生对快速基因组测序 (RGS) 临床效用的调查结果。 201 名婴儿中有 154 名 (77%) 达到了主要终点——临床医生认为 RGS 有用。阳性和阴性测试均被评为具有临床实用性(分别为 45 项中的 42 项 [93%] 和 156 项中的 112 项 [72%])。医生报告称,RGS 改变了 57 名 (28%) 婴儿的临床管理,特别是接受 urWGS (p = 0.0001) 和阳性检测 (p < 0.00001) 的婴儿。 32 名 (15%) 婴儿的结局被认为因 RGS 而改变。阳性测试比阴性测试更频繁地改变结果 (p < 0.00001)。在逻辑回归模型中,当与管理变化相关时,RGS 被认为有用的可能性增加了 6.7 倍(95% CI 1.8-43.3)。当结果为阳性(95% CI 4.7-22.4)且周转时间较短(比值比 0.92,95% CI 0.85-0.99)时,管理变化的可能性增加 10.1 倍。 RGS 很少导致临床医生感到家庭混乱或痛苦(207 名家庭中的 6 名[3%])。总之,临床医生认为对 ICU 中患有未知病因疾病的婴儿进行一级 RGS 具有较高的临床实用性和较低的伤害可能性。无论结果是阳性还是阴性,RGS 都被认为是有益的。

更新日期:2020-11-06
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