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

描述(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了。因此，它的临床和社会影响在很大程度上是未知的。这项拟议的研究旨在增加有关这些对危重新生儿影响的科学知识。考虑到疾病的严重性，这些人口可能会很大程度上受益于WGS。这项拟议的临床研究是一项前瞻性、随机、部分盲目的研究，对儿童慈善医院急性患病新生儿使用STATseq的风险和好处进行了定量和定性评估。STATseq是一种为期两天的基因组测试。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。总体目标将提供对急症新生儿快速诊断WGS的作用的细微差别的理解，包括对广泛的NICU人群和亚人群的相对诊断敏感性和管理变化、准确性、重复性以及先证者WGS和家族性三联体的相对价值。技术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效率，缩短诊断时间，以及临床医生对实施STAT-SEQ带来的管理变化的看法。最后，本研究将使用结构方程模型调查父母和临床医生对STAT-SEQ的感知价值。这些研究还旨在对参与者进行长期持续的评估(超过当前的资助期)，并对其他样本类型进行评估(通过生物信息库)。长期持续研究将测试对长期发病率、死亡率、生活质量和护理成本的影响。我们希望研究结果将足以为医生在3级和4级NICU中采用WGS和提供者补偿WGS提供证据基础。 相关性：6.7%的新生儿需要在新生儿重症监护病房接受护理，这一群体的发病率和死亡率是所有儿科群体中最高的。考虑到疾病的严重性，这些新生儿可能会从使用全基因组测序进行快速基因诊断中获益最多。因此，我们建议研究快速WGS技术在这一人群中的好处和风险。

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. RELEVANCE: 6.7% of newborns require care in a neonatal intensive care unit and this group has the highest morbidity and mortality of any pediatric group. Given the severity of illness, these newborns may have the most to gain from fast genetic diagnosis through the use of whole genome sequencing. Thus, we propose to examine the benefits and risk of rapid WGS technology in this population.