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

Acutely III 新生儿 2 天基因组结果的临床和社会意义

• 批准号: 9205327
• 负责人: Stephen Francis Kingsmore
• 金额: $ 125万
• 依托单位: RADY PEDIATRIC GENOMICS & SYSTEMS MEDICINE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9205327
• 关键词: Clinical; Social; Implications; day; Genome

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.

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，其临床和社会影响在很大程度上是未知的。这项拟议的研究旨在增加对这些急性病新生儿影响的科学知识。考虑到疾病的严重程度，这一人群可能会从WGS中受益匪浅。拟议的临床研究是一项前瞻性、随机、部分设盲研究，对儿童慈善医院的急性病新生儿使用STATseq（一种为期2天的基因组检测）的风险和获益进行了定量和定性评估。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。总体目标将提供一个微妙的理解的作用，快速诊断WGS的急性病新生儿，包括相对诊断灵敏度和管理的变化，为广泛的NICU人群和亚群，准确性，再现性和相对价值的先证者WGS和家族三联体。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调查STAT-seq在父母和临床医生中的感知价值。这些研究还旨在长期持续评估入组者（超过当前资助期）和其他样本类型（通过生物储存库）。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。我们希望研究结果足以为3级和4级NICU的医生采用和提供者报销WGS提供证据基础。