ECG Device for LQTS Screening in Newborns, Phase II

描述（由申请人提供）：先天性长QT综合征（LQTS）被认为发生在1 / 2000的婴儿中，导致10-15%的婴儿猝死综合征（SIDS）死亡。心电图（ECGs）可以在致命心脏事件发生前检测到LQTS。在我们的第一阶段STTR项目中，我们成功开发并测试了一种用于新生儿LQTS筛查的ECG设备。这种设备，现在被称为QTScreen，完全按照我们第一阶段提案的规定生产。第一阶段的两个具体目标都已完成，所有里程碑都如期达到。在这个II期提案中，我们的目标是证明QTScreen在美国新生儿LQTS筛查中的有效性，从而使QTScreen能够成为商业化的产品和服务。为了实现我们的目标，我们提出了一项临床试验，以验证QTScreen设备用于LQTS筛查，评估新生儿筛查策略，并确定南加州LQTS的流行病学，从而确定潜在市场。在Aim 1中，我们将完善QTScreen用于大型临床试验。这个

DESCRIPTION (provided by applicant): The congenital long QT syndrome (LQTS) is thought to occur in 1 in 2,000 infants and cause 10-15% of deaths from SIDS (sudden infant death syndrome). Electrocardiograms (ECGs) can detect LQTS before fatal cardiac events happen. In our Phase I STTR project, we successfully developed and tested an ECG device designed for LQTS screening in newborns. This device, now called QTScreen, was produced exactly as specified in our Phase I proposal. Both Specific Aims in Phase I were completed and all milestones were reached on schedule. In this Phase II proposal, our goal is to demonstrate the effectiveness of the QTScreen for LQTS screening in newborns in the U.S., so that the QTScreen can become a commercialized product and service. To achieve our goal, we propose a clinical trial to validate the QTScreen device for LQTS screening, assess strategies for newborn screening, and define the epidemiology of LQTS in the Southern California -- and thus the potential market. In Aim 1, we will perfect the QTScreen for use in a large clinical trial. The refinements will enhance QTScreen function and make it more user-friendly. The design will comply with FDA standards and allow scalable production. In Aim 2, we will show the effectiveness of QTScreen for LQTS screening in newborns in Southern California. We will conduct a clinical trial on 4,000 babies. Results will establish the prevalence of LQTS in Southern California, and validate QTScreen as a newborn screening tool. In Aim 3, we will identify strategies to understand and minimize false positive screens. False positive results cause unneeded parental anxiety and raise costs due to expensive genetic testing. Our strategies to minimize false positive results are to: (1) identify the optimal QTc threshold for rescreening and gene testing; and (2) identify common single nucleotide variants that affect QT intervals in newborns, apart from LQTS mutations. Expected outcomes of Phase II are a validated QTScreen device for newborn screening, a marketable product ready for FDA filing, and valuable data on LQTS occurrence in the U.S. With Phase II results, we will seek investments and apply for an NHLBI Phase IIB Small Market Award. In Phase IIB, we will propose a multi-center trial for nationwide newborn LQTS screening in the U.S. and cost effectiveness analyses.