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）：在很大程度上忽略了新生儿的整个基因组测序（WGS）的大规模研究。因此，它的临床和社会影响在很大程度上是未知的。拟议的研究旨在增加对这些对急性疾病新生儿的影响的科学知识。考虑到疾病的严重性，该人群可能会从WGS中受益。拟议的临床研究是一项前瞻性，随机，部分失明的研究，对使用STATSEQ的风险和益处进行了定量和定性评估，Statseq是一项为期2天的基因组测试，在儿童怜悯医院急性病。研究参与者包括新生儿，他们的父母和临床医生照顾他们。总体目的将为急性疾病新生儿的快速诊断WG的作用提供细微的理解，包括相对诊断的敏感性和对广泛的NICU种群和亚种群的管理变化，准确性，可重复性以及概率WGS和家族三合会的相对价值。该技术的目的包括提高诊断灵敏度而不牺牲快速的周转时间。临床目的包括研究增加的诊断产量，诊断时间较短以及临床医生对实施STAT-SEQ导致的管理变化的看法。最后，该研究将使用结构方程建模调查父母和临床医生在父母和临床医生中的感知价值。该研究还设计用于长期延续参与者评估（超出当前资金期）和其他样本类型（通过生物存储库）。长期延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。我们希望该研究结果足以为在3级和4级NICUS中的医师收养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中进行护理，该组的发病率和死亡率最高。鉴于疾病的严重程度，这些新生儿可能通过使用整个基因组测序从快速遗传诊断中获得最大的收益。因此，我们建议研究该人群中快速WGS技术的好处和风险。