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

• 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
• 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

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.

项目摘要 该提案旨在为候选人在临床和医学领域的独立学术生涯做好准备。 翻译研究候选人的长期目标是为患有胆道疾病的儿童发现创新的解决方案。 闭锁和其他肝脏疾病。候选人在基础科学研究方面接受过博士培训，他关心 病人在一个刺激的环境，使他暴露于全方位的儿科肝脏疾病。现在 候选人寻求临床和转化研究技术的正式培训，使他能够综合 临床观察和患者数据，并开发新的诊断，治疗和预防策略。 该项目的近期目标有三个方面： 1)通过正式的课程，研究经验，获得临床和转化研究技能， 导师指导; 2)为未来的研究开发想法，这可以作为R 03或R 01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， 儿科肝病学的成功职业道路将作为模板。 为了实现这一点，候选人已经制定了严格的职业发展计划， 同时评估一种新的新生儿胆道闭锁（BA）筛查。BA是一种严重的肝脏疾病， 发病率和死亡率，是美国儿科肝移植的主要适应症。如果BA是 早期诊断和治疗，患有疾病的婴儿可以延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，因为这种疾病在出生后的头几个星期很难识别。 之前，候选人观察到BA婴儿的直接或结合胆红素水平升高， 并提出这种简单的测试可以用来筛查新生儿的疾病。 职业发展计划将使候选人具备必要的知识和技能， 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 研究和解释大量的人口数据，通过筛选10个不同出生的102，000名新生儿， 医院的候选人还将参加正式的课程，学习成本效益的理论和实践 研究，然后创建复杂的模型，模拟有和没有筛选的结果， 包括屏幕的相关成本。最后，候选人将在临床上学习专业技术 化学实验室，以及如何评估其效用，在测试血斑样本是否可以 用于BA筛选试验。 在培训期结束时，候选人应接受良好的培训，以解决 临床和转化研究水平的儿科肝病学。他应该有很多潜在的途径 进一步的研究，包括表征胆道闭锁的早期阶段，产生有效的算法 为了诊断胆道闭锁，从国家新生儿筛查中大规模检测血斑样本， 实验室，并可能在国家一级实施一个普遍的新生儿筛查计划。 他还将受益于该领域一位久经考验的领导者多年的密切指导。这些经验 应该准备候选人申请独立的资金，并帮助启动他的研究生涯，作为一个 一位成功的医生科学家专注于改善肝病儿童的生活。