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2 - 4每1,000活足月新生儿，并负责19%的500万新生儿死亡，每年在世界各地。在理解疾病过程的病理生理学和研究潜在的神经保护策略方面已经做出了重大努力。生命的最初几个小时已被确定为一个关键时期，在此期间，干预具有改善结果的最佳潜力。然而，转化研究和临床护理都受到缺乏客观有效的工具来实时床边评估神经损伤的限制。为了满足这一需求，我们开发了一种新的多参数EEG为基础的指数，它结合了频谱和时间分析到一个统一的衡量神经损伤。在仔猪模型中评价该指数。经调整的算法证明，识别组织病理学定义的不良结局的灵敏度和特异性分别为90%和95%。然后，我们使用围产期窒息后NICU的EEG记录来评估该指数。盲法专家对信号的视觉解读以及Sarnat评分用作基准。建立了一系列受试者-操作者曲线，在所有情况下，调整算法的灵敏度和特异性均保持在80%以上。我们现在打算继续进行II期竞争，目标只有一个：获得FDA对Infinite I-2020 EEG系统（带CHI/B分析）的批准。为了获得所需的数据，以支持我们所需的标签用于评估脑病新生儿，我们将进行临床研究。这将检验两个假设：1）在监测的第1小时内，该指数可以评估出生后7天MRI所定义的神经损伤的严重程度，其灵敏度和准确度高于任何其他现有测量; 2）在出生后第1天测量的指数可以评估神经发育结果。如果我们成功了，所得到的设备将能够对患者进行神经保护研究分层，并最终确定哪些患者将从治疗中受益。此外，应注意的是，申报的监查员将是第一个获得此类标签监管许可的监查员。这个单一的终点定义了项目的成功完成。神经保护是治疗围产期窒息的新兴疗法。然而，早期识别可以从神经保护治疗中受益的患者是有限的。该项目旨在实现FDA批准的基于EEG的监测系统，可作为临床研究工具，以进一步加强对围产期窒息后新生儿的诊断评估。

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.