Neonatal Neurological Monitor - Regulatory Approval

描述（由申请人提供）：新生儿神经监测：监管批准围产期窒息发生在每1000个足月新生儿中2 - 4个，占全球每年500万新生儿死亡的19%。重要的努力已经进入了解疾病过程的病理生理学和研究潜在的神经保护策略。生命最初的几个小时被认为是干预最有可能改善结果的关键时期。然而，由于缺乏一种客观有效的神经损伤床边实时评估工具，转化研究和临床护理都受到了限制。为了满足这一需求，我们开发了一种新的基于脑电图的多参数指数，该指数将频谱和时间分析结合到神经损伤的统一测量中。该指标在仔猪模型中进行了评估。调整后的算法在识别组织病理学定义的不良结果方面的敏感性和特异性分别为90%和95%。然后我们使用新生儿重症监护病房围产期窒息后的脑电图记录来评估该指数。盲法专家对信号的视觉解释以及萨尔纳特评分被用作基准。建立了一系列的接收者-操作者曲线，在所有情况下，调整后的算法的灵敏度和特异性都保持在80%以上。我们现在打算追求II期竞争延续，目标只有一个：获得FDA批准Infinite的I-2020脑电图系统与CHI/b分析。为了获得所需的数据来支持我们期望的用于脑病新生儿评估的标签，我们将进行一项临床研究。这将检验两个假设：1)在监测的第一个小时内，该指数可以评估7天前MRI所定义的神经损伤的严重程度，比任何其他现有的测量方法都具有更高的灵敏度和准确性；2)在出生第1天测量的指标可以评估神经发育结局。如果我们是成功的，所产生的设备将使患者分层神经保护研究，并最终确定患者谁将受益于治疗。此外，应该指出的是，拟议的监测器将是第一个获得此类标签监管许可的监测器。这个单一端点定义了项目的成功完成。神经保护是治疗围产期窒息的一种新兴疗法。然而，能够从神经保护治疗中获益的患者的早期识别是有限的。本项目旨在获得FDA批准一种基于脑电图的监测系统，该系统可作为临床研究工具，进一步加强新生儿围产期后窒息的诊断评估。

DESCRIPTION (provided by applicant): Neonatal Neurological Monitor: Regulatory Approval Perinatal asphyxia occurs in 2 - 4 per 1,000 live term newborns, and is responsible for 19% of the 5 million neonatal deaths per year worldwide. Significant effort has gone into understanding the pathophysiology of the disease process and to investigate potential neuroprotection strategies. The first hours of life have been identified as a critical period during which intervention has the best potential for improving outcome. However, both translational research and clinical care have been limited by the lack of an objective validated tool for real-time bedside evaluation of neurological injury. To address this need, we developed a novel multi-parametric EEG-based index which incorporates both spectral and temporal analysis into a unified measure of neurological injury. This index was evaluated in a piglet model. The tuned algorithm demonstrated a sensitivity and specificity of 90% and 95% respectively to identify poor outcome as defined by histopathology. We then evaluated the index using EEG recordings from the NICU following perinatal asphyxia. Visual interpretation of the signal by a blinded expert as well as the Sarnat score were used as benchmarks. A series of receiver- operator curves were created, and the sensitivity and specificity of the tuned algorithm remained above 80% in all cases. We now intend to pursue a Phase II competing continuation with a single aim: To obtain FDA clearance for Infinite's I-2020 EEG system with CHI/b analysis. To obtain the data needed to support our desired labeling for use in the assessment of encephalopathic newborns, we will undertake a clinical study. This will test two hypotheses: 1) within the 1st hour of monitoring, the index can assess the severity of neurological injury as defined by the MRI at 7 days of life with greater sensitivity and accuracy than any other currently available measure; and 2) the index measured during the 1st day of life can assess neurodevelopmental outcome. If we are successful, the resultant device will enable stratification of patients for neuroprotection studies as well as for eventual identification of patients who would benefit from therapy. Additionally, it should be noted the proposed monitor will be the first with regulatory clearance for such labeling. This singular endpoint defines successful completion of the project. Neuroprotection is an emerging therapy for treating perinatal asphyxia. However, early identification of patients which can benefit from neuroprotective treatment is limited. This project aims to achieve FDA approval of an EEG based monitoring system that can serve as a clinical research tool to further enhance diagnostic evaluation of neonates post perinatal asphyxia.