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: 8585138
• 负责人: Stephen Francis Kingsmore
• 金额: $ 118.31万
• 依托单位: CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
• 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/8585138
• 关键词: Adoption; Benefits and Risks; Blinded; Caring; Child; Childhood; Clinical; Clinical Research; Diagnosis; Diagnostic; Diagnostic Sensitivity; Equation; Funding; Genetic; Genome; Hospitals; Knowledge; Living Costs; Modeling; Morbidity - disease rate; Neonatal Intensive Care Units; Newborn Infant; Parents; Participant; Perception; Physicians; Population; Provider; Quality of life; Randomized; Relative (related person); Reproducibility; Risk-Benefit Assessment; Role; Sampling; Severity of illness; Technology; Testing; Time; Triad Acrylic Resin; design; evidence base; genome sequencing; improved; mortality; neglect; neonate; proband; prospective; repository; social implication

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.

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了。因此，其临床和社会影响在很大程度上尚不清楚。拟议的研究旨在增加对这些对重症新生儿影响的科学认识。考虑到疾病的严重程度，这一人群可能会从全基因组测序中受益匪浅。拟议的临床研究是一项前瞻性、随机、部分盲法研究，对儿童慈善医院重症新生儿使用 STATseq（一项为期 2 天的基因组测试）的风险和益处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。总体目标将提供对快速诊断 WGS 对急症新生儿的作用的细致了解，包括对广大 NICU 人群和亚人群的相对诊断敏感性和管理变化、先证者 WGS 和家族三联征的准确性、可重复性以及相对价值。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率、缩短诊断时间以及临床医生对 STAT-seq 实施带来的管理变化的看法。最后，该研究将使用结构方程模型来调查 STAT-seq 在父母和临床医生中的感知价值。这些研究还旨在对参与者（超出当前资助期限）和其他样本类型（通过生物存储库）进行长期持续评估。长期持续研究将测试对长期发病率、死亡率、生活质量和护理费用的影响。我们希望研究结果足以为 3 级和 4 级 NICU 中医生采用 WGS 和提供者报销提供证据基础。 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，该群体的发病率和死亡率是所有儿科群体中最高的。考虑到疾病的严重程度，这些新生儿可能从通过使用全基因组测序的快速基因诊断中获益最多。因此，我们建议研究快速全基因组测序技术在该人群中的益处和风险。