Diagnosis of Neonatal Opioid Withdrawal Syndrome (NOWS) and development of a NOWS-App

项目摘要 PedialyDx Inc.建议复制以前的研究成果，并开发一种商业产品， 协助诊断新生儿阿片类药物戒断综合征（NOWS），即婴儿 出生后不久，由于胎儿突然停止接触阿片类药物，NOWS有 成为一个重大的公共卫生问题，从2004年的每千名新生儿1.6例增加到每千名新生儿8.8例 2016年，相关医院费用从2000年的1.9亿美元增加到2009年的7.2亿美元。准确 NOWS的诊断很重要，因为假阳性可能导致婴儿不必要地接受 药物治疗，相应的延长住院时间和大量费用，或假- 阴性会导致婴儿在应该得到治疗的时候得不到治疗，可能导致严重的医疗问题。 不幸的是，目前诊断NOWS的方法，无论是基于“黄金”的 标准的”Finnegan评分系统“或非基于网络的“East、Sleep和Console”， 由于其主观性而受到限制。使用专有的声学分析软件和机器学习（ML） 算法，我们的团队已经确定了一个初步的“哭签名”有关婴儿哭声学芬尼根 精确度0.81 PedialyDx的NOWS应用程序将为NOWS儿童提供更好的护理， 创新：1）使用声哭分析的更客观的评估将导致更准确的诊断， 治疗（更少的假阳性，更少的假阴性，更精确的住院时间）和2）节省 时间，从而节省成本，在管理婴儿与NOWS。我们的初步数据显示 在一个单一的控制临床环境中收集，这已经证明了我们的算法可以 客观地评估婴儿的哭声。下一步，我们将通过扩大我们的NOWS应用程序的商业化， 通过从现实世界的设置中收集数据来优化我们的NOWS ML算法。在 目的1，我们将进行一项多中心研究（7个中心），以扩展婴儿哭声作为 现在。在目标2中，我们将完成NOWS-app的开发。成功完成该项目 将导致我们的NOWS-App产品准备提交给FDA。本申请中提出的工作 还将允许PedialyDx采取重要步骤，推进其婴儿啼哭技术平台， 其他条件的产品，如自闭症和其他发育障碍，绞痛和疼痛的筛查。

PROJECT SUMMARY PedialyDx Inc. proposes to replicate previous research findings and develop a commercial product that can assist in the diagnosis of Neonatal Opioid Withdrawal Syndrome (NOWS), the withdrawal that infants experience shortly after birth due to the abrupt discontinuation of fetal exposure to opioids. NOWS has become a significant public health problem, increasing from 1.6 per 1000 births in 2004 to 8.8 per 1000 births in 2016, with associated hospital charges increasing from $190M in 2000 to $720M in 2009. Accurate diagnosis of NOWS is important because false-positives can result in babies unnecessarily receiving pharmacological treatment with corresponding prolonged hospitalization and substantial cost, or false- negatives result in babies not being treated when they should, potentially leading to serious medical problems. Unfortunately, current methods to diagnose NOWS, whether pharmacologically based such as the “gold standard” Finnegan scoring system, or non-pharmacologically based such as “East, Sleep and Console” are limited because of their subjectivity. Using proprietary acoustic analysis software and Machine Learning (ML) algorithms, our team has identified a preliminary “cry signature” relating baby cry acoustics to the Finnegan with .81 accuracy. PedialyDx’s NOWS-app will deliver improved care for children with NOWS through 2 innovations: 1) more objective assessment using acoustic cry analysis will lead to more accurate diagnosis and treatment (fewer false positives, fewer false negatives, and more precise hospitalization stays) and 2) save time, leading to cost savings, in the management of babies with NOWS. Our preliminary data has been collected in a single controlled clinical setting, which has demonstrated proof of concept that our algorithm can objectively assess baby cries. Next, we will advance the commercialization of our NOWS-app by expanding upon our existing dataset by collecting data from real-world settings to optimize our ML algorithm for NOWS. In Aim 1, we will conduct a multi-center study (7 sites) to extend the research of baby cry as an indicator of NOWS. In Aim 2, we will complete the development of the NOWS-app. Successful completion of this project will result in our NOWS-App product ready for submission to the FDA. The work proposed in this application will also allow PedialyDx to take important steps toward advancing its baby cry technology platform to enable products for other conditions, such as screening for autism and other developmental disorders, colic and pain.