Clinical and Social Implications of 2-day Genome Results in Acutely III Newborns

描述（由申请人提供）：新生儿全基因组测序（WGS）的大规模研究在很大程度上被忽视。因此，其临床和社会意义在很大程度上是未知的。拟议的研究旨在增加这些对急性新生儿影响的科学知识。鉴于疾病的严重程度，这一人群可能会从WGS中获益。拟议的临床研究是一项前瞻性、随机、部分盲法研究，对儿童慈善医院急性新生儿使用STATseq（2天基因组检测）的风险和益处进行定量和定性评估。研究参与者包括新生儿、他们的父母和照顾他们的临床医生。总体目标将提供对快速诊断WGS在急性新生儿中的作用的细致理解，包括对广大新生儿重症监护室人群和亚人群的相对诊断敏感性和管理变化，准确性，可重复性以及先证WGS和家族三联体的相对价值。该技术的目标包括在不牺牲快速周转时间的情况下提高诊断灵敏度。临床目标包括提高诊断率，缩短诊断时间，以及临床医生对实施STAT-seq导致的管理变化的看法。最后，本研究将使用结构方程模型来调查父母和临床医生对STAT-seq的感知价值。这些研究还设计用于长期持续评估注册者（超过当前资助期）和额外的样本类型（通过生物储存库）。长期继续研究将测试对长期发病率、死亡率、生活质量和护理费用的影响。我们希望研究结果足以为医生在3级和4级nicu中采用WGS和提供者报销提供证据基础。

DESCRIPTION (provided by applicant): Large scale studies of whole genome sequencing (WGS) in neonates have largely been neglected. Thus, its clinical and social implications are largely unknown. The proposed study aims to increase scientific knowledge of these implications for acutely ill neonates. This population may stand to benefit largely from WGS given the severity of illness. The proposed clinical study is a prospective, randomized, partially blinded study which has both quantitative and qualitative assessments of the risks and benefits of the use of STATseq, a 2-day genome test, in acutely ill neonates at Children's Mercy Hospital. Study participants include neonates, their parents and clinicians caring for them. The overall aims will provide a nuanced understanding of the role of rapid diagnostic WGS for acutely ill neonates, including relative diagnostic sensitivity and change in management both for broad NICU populations and subpopulations, accuracy, reproducibility, and relative value of proband WGS and familial triads. The technologic aims include improving diagnostic sensitivity without sacrificing the rapid turnaround time. The clinical aims include looking at increased diagnostic yield, shorter time to diagnosis and clinician perception of management changes that result from implementation of STAT-seq. Finally, the study will investigate the perceived value of STAT-seq in parents and clinicians using structural equation modeling. The studies also are designed for long term continuation of assessment of the enrollees (beyond the current funding period) and in additional sample types (via a bio repository). Long term continuation studies will test effects on long term morbidity, mortality, quality of life and cost of care. We hope that the study results will be sufficient to provide an evidence base for physician adoption and provider reimbursement of WGS in Level 3 and 4 NICUs.