Assessment of a Novel Newborn Screening Tool for Biliary Atresia

新型新生儿胆道闭锁筛查工具的评估

基本信息

批准号：
9241611
负责人：
SANJIV HARPAVAT
金额：
$ 18.17万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-16 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9241611
关键词：
1 year old Accounting Address Algorithms Applications Grants Basic Science Biliary Biliary Atresia Bilirubin Biological Assay Birth Blood Blood Tests Career Choice Child Childhood Clinical Clinical Chemistry Clinical Research Communication Complex Country Data Databases Decision Making Decision Modeling Decision Trees Development Development Plans Diagnosis Disease Disease Outcome Doctor of Philosophy Early treatment Effectiveness Enrollment Environment Ethnic Origin Feces Foundations Funding Future Goals Health Hepatology Hospitals Individual Infant Instruction Intervention Investigation K-Series Research Career Programs Knowledge Laboratories Learning Life Liver Liver diseases Mass Spectrum Analysis Measurement Measures Medicaid Mentors Modeling Morbidity - disease rate Multicenter Studies Neonatal Screening Newborn Infant Outcome Patient Care Patients Physicians Policy Maker Population Population Heterogeneity Prevention strategy Probability Provider Publishing Race Research Research Infrastructure Research Technics Sampling Scientist Serum Spottings Symptoms Techniques Testing Texas Time Training Translational Research Transplantation United States career career development clinical epidemiology cost cost effective cost effectiveness design experience experimental study improved improved outcome innovation liver injury liver transplantation mortality novel novel diagnostics operation prevent programs prospective test screening skills statistics success tandem mass spectrometry theories tool treatment strategy

项目摘要

PROJECT SUMMARY This proposal is designed to prepare the candidate for an independent academic career in clinical and translational research. The candidate’s long term goal is to discover innovative solutions for children with biliary atresia and other liver diseases. The candidate has PhD training in basic science research, and he cares for patients in a stimulating environment that exposes him to the full spectrum of pediatric liver disorders. Now the candidate seeks formal training in clinical and translational research techniques, to allow him to synthesize clinical observations and patient data and develop novel diagnostic, treatment, and prevention strategies. The immediate goals of this project are threefold: 1) Acquire clinical and translational research skills through formal coursework, research experience, and mentor-guided instruction; 2) Develop ideas for future research, which can serve as the basis for a R03 or R01 grant application to initiate an independent career; and 3) Learn analytical, communication, and decision-making skills from an accomplished mentor, whose successful career path in pediatric hepatology will serve as a template. To accomplish this, the candidate has created a rigorous career developmental plan to occur concurrently while assessing a novel newborn screen for biliary atresia (BA). BA is a serious liver condition with significant morbidity and mortality, and is the leading indication for pediatric liver transplantation in the US. If BA is diagnosed and treated early, infants with disease can delay or even avoid need for liver transplantation; however, infants are often diagnosed later because the disease is difficult to recognize in the first weeks of life. Previously, the candidate observed that infants with BA have elevated direct or conjugated bilirubin levels at birth, and proposed that this simple test could be used to screen newborns for disease. The career development plan will equip the candidate with the necessary knowledge and skills to fully assess newborn direct/conjugated bilirubin screening for BA. The candidate will learn how to conduct multi-center studies and interpret large amounts of population data, by screening 102,000 newborns from 10 different birth hospitals. The candidate will also take formal coursework to learn the theory and practice of cost-effective studies, and then create sophisticated models simulating outcomes with and without screening which also incorporate the screen’s associated costs. Finally, the candidate will learn specialized techniques in the clinical chemistry laboratory and how to evaluate their utility, in the context of testing whether blood spot samples can be used for the BA screening test. At the conclusion of the training period, the candidate should be well trained to address complex problems in pediatric hepatology at a clinical and translational research level. He should have many potential avenues of further investigation, including characterizing the early stages of biliary atresia, generating efficient algorithms for diagnosing biliary atreia, testing blood spot samples on a large scale from state newborn screening laboratories, and potentially implementing a universal newborn screening program for BA at the national level. He will also have benefitted from years of close instruction by a proven leader in the field. These experiences should prepare the candidate to apply for independent funding, and help launch his research career as a successful physician scientist focused on improving the lives of children with liver diseases.

项目概要该提案旨在帮助候选人为临床和临床领域的独立学术生涯做好准备候选人的长期目标是为胆病儿童找到创新的解决方案。该候选人接受过基础科学研究的博士学位培训，他关心的是闭锁和其他肝脏疾病。患者处于一个刺激的环境中，使他接触到各种小儿肝脏疾病。候选人寻求临床和转化研究技术方面的正式培训，以使他能够综合临床观察和患者数据，并制定新的诊断、治疗和预防策略。该项目的近期目标有三个： 1) 通过正式课程、研究经验和获得临床和转化研究技能导师指导的教学； 2) 为未来的研究提出想法，这可以作为 R03 或 R01 资助申请的基础开始独立的职业生涯；以及 3) 从一位有成就的导师那里学习分析、沟通和决策技能，他的导师儿科肝病学的成功职业道路将作为模板。为了实现这一目标，候选人制定了严格的职业发展计划，同时进行同时评估胆道闭锁 (BA) 的新型新生儿筛查 BA 是一种严重的肝脏疾病，具有显着的临床意义。发病率和死亡率，并且是美国儿童肝移植的主要适应症。早期诊断和治疗，患病婴儿可以推迟甚至避免肝移植的需要；然而，婴儿往往较晚才被诊断出来，因为这种疾病在生命的最初几周内很难识别。此前，候选人观察到患有 BA 的婴儿的直接胆红素或结合胆红素水平升高出生，并提出这种简单的测试可用于筛查新生儿的疾病。职业发展计划将为候选人提供必要的知识和技能，以充分评估新生儿直接/结合胆红素筛查 BA 考生将学习如何进行多中心。通过筛查 10 个不同出生的 102,000 名新生儿，研究并解释大量人口数据候选人还将参加正式课程来学习成本效益的理论和实践。研究，然后创建复杂的模型来模拟有或没有筛查的结果，这也最后，候选人将学习临床专业技术。化学实验室以及如何评估其效用，以测试血斑样本是否可以用于 BA 筛选测试。培训期结束时，候选人应接受良好的培训，能够解决以下领域的复杂问题：临床和转化研究水平的儿科肝病学他应该有许多潜在的途径。进一步研究，包括表征胆道闭锁的早期阶段，生成有效的算法用于诊断胆道闭锁，大规模检测国家新生儿筛查的血斑样本实验室，并有可能在国家层面实施一项针对 BA 的普遍新生儿筛查计划。他还将受益于该领域久经考验的领导者多年的密切指导。应该让候选人做好申请独立资助的准备，并帮助他作为一名研究人员开始他的研究生涯成功的医师科学家专注于改善患有肝病的儿童的生活。