PKU Now-Connect: An intelligent digital ecosystem to improve health outcomes in Phenylketonuria

摘要 苯丙酮尿症（PKU）是一种遗传性疾病，导致不能代谢必需的 氨基酸苯丙氨酸（Phe）。不受控制的血液Phe的后果包括智力残疾， 癫痫、皮肤病、震颤、多动、脑电图异常、行为问题、执行功能障碍， 和精神疾病PKU影响大约1/24，000人，估计有450，000人 国际吧在美国，PKU发生在每10，000名新生儿中的1名。推荐PKU患者 维持血中苯丙氨酸水平在2-6 mg/dL（121-363 µmol/L）。这需要一个专门的饮食组合， 药物治疗和门诊。对于患者来说，管理他们的血液Phe水平是一个重大挑战，这主要是由于 血液中苯丙氨酸水平缺乏实时反馈。第一阶段SBIR应用程序的目的是开发 并论证了以远程监控为核心的北大管理平台的可行性。 现有的床旁（POC）设备。北京大学现在连接将包括一个POC测量仪， 一个配对的移动的应用程序，用于显示结果和跟踪Phe摄入量，以及一个互动的 与专家、营养师或医疗保健提供者连接的网络仪表板。具体目标是 应用程序是：1）完成北大现在移动的应用程序，2）设计和整合网络仪表板与移动的应用程序， 3）用户体验和平台可用性测试。现有的POC测量仪（先前的第二阶段合同，项目 Grant R44 GM 126593）和原型移动的应用程序将用作基础模板。在第一阶段， 将设计和测试移动的应用程序，用于通过POC仪跟踪Phe摄入量和血液Phe水平。接下来， 用于存储、显示和转换数据的数据库和网络仪表板将被设计、测试， 安装到云服务器上。最后，将要求招募的受试者使用PKU Now-Connect评估 平台的用户体验和可用性。来自芝加哥儿童医院的专家意见 Phenylalanine Families and Researchers Exploring Evidence（PHEFREE）Consortium和National PKU 联盟（NPKUA）将获得。在第二阶段，与波士顿儿童医院合作的临床研究 和匹兹堡大学医学中心将完成，以验证北大现在连接的可行性 在PKU患者的临床环境中。该数据库将扩大到包括安全的患者信息， 扩大药物和症状的跟踪，并与医疗保健提供者直接沟通。如果 平台成功，FDA指南“器械软件功能的上市前提交内容”发布 Nov. 4，2021年，以及9月发布的“移动的和医疗应用程序的设备软件功能政策”27, 2019年，将遵循510 K提交。北京大学现在连接将产生重大的积极影响， PKU患者及其护理人员。

Abstract Phenylketonuria (PKU) is an inherited genetic disorder that results in an inability to metabolize the essential amino acid phenylalanine (Phe). Consequences of uncontrolled blood Phe include intellectual disabilities, seizures, skin disorders, tremors, hyperactivity, EEG abnormalities, behavioral problems, executive dysfunction, and psychiatric disorders. PKU affects approximately 1 in 24,000 people and an estimated 450,000 individuals worldwide. In the United States, PKU occurs in 1 out of every 10,000 newborns. PKU patients are recommended to maintain blood Phe levels within 2-6 mg/dL (121-363 µmol/L). This requires a combination of specialized diet, medication, and clinic visits. It is a significant challenge for patients to manage their blood Phe levels due mainly to the lack of real-time feedback on blood Phe levels. The purpose of this Phase I SBIR application is to develop and demonstrate the feasibility of a remote monitoring platform for PKU management centered around an existing point-of-care (POC) device. The PKU Now-Connect will be comprised of a POC meter for measuring blood Phe concentrations, a paired mobile app for displaying results and tracking Phe intake, and an interactive web dashboard with connectivity to experts, dietitians, or healthcare providers. The specific aims for this application are: 1) Finalize the PKU Now Mobile App, 2) Design and Integrate Web Dashboard with Mobile App, and 3) User Experience and Platform Usability Tests. An existing POC meter (previous Phase II award, Project Grant R44GM126593) and prototype mobile app will be used as a base template. In Phase I, a user-friendly mobile app will be designed and tested for tracking Phe intake and blood Phe levels via the POC meter. Next, a database and web dashboard for storing, displaying, and transforming data will be designed, tested, and implemented to a cloud server. Finally, recruited subjects will be asked to use the PKU Now-Connect to assess the user experience and usability of the platform. Expert opinions from the Children’s Hospital of Chicago, the Phenylalanine Families and Researchers Exploring Evidence (PHEFREE) Consortium, and the National PKU Alliance (NPKUA) will be obtained. In Phase II, clinical studies in collaboration with Boston Children’s Hospital and University of Pittsburgh Medical Center will be completed to validate the feasibility of the PKU Now-Connect in a clinical setting with PKU patients. The database will be expanded to include secured patient information, expanded tracking of medication and symptoms, and direct communication with healthcare providers. If the platform is successful, FDA Guidance “Content of Premarket Submission for Device Software Functions” issued Nov. 4, 2021, and “Policy for Device Software Functions for Mobile and Medical Applications” issued Sept. 27, 2019, will be followed for 510 K submission. The PKU Now-Connect will have a significant, positive impact on PKU patients and their caregivers.