Innovative Statistical Models for Development of First Huntington's Disease Progression Risk Assessment Tool

用于开发第一个亨廷顿病进展风险评估工具的创新统计模型

基本信息

批准号：
9224488
负责人：
Tanya Pamela Garcia
金额：
$ 19.08万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9224488
关键词：
AIDS Dementia Complex Alzheimer&apos s Disease Americas Area Assessment tool Attenuated Big Data Biological Markers Biometry Books Brain Brain region Clinical Clinical Trials Clinical Trials Design Complex Data Data Set Deterioration Development Diagnosis Dimensions Disease Disease Progression Early Intervention Future Generations Goals Human Biology Huntington Disease Impaired cognition Impairment Individual Knowledge Lead Learning Magnetic Resonance Imaging Masks Measurement Measures Medicine Mendelian disorder Mentors Methodology Methods Modeling Motor Nerve Degeneration Neurodegenerative Disorders Neuroepidemiology Neurologic Neurology Neurosciences Outcomes Research Parkinson Disease Pattern Penetrance Performance Precision Medicine Initiative Publications Research Research Personnel Risk Risk Assessment Sample Size Societies Statistical Data Interpretation Statistical Methods Statistical Models Structure Symptoms System Texas Therapeutic Intervention Time Training United States National Institutes of Health Universities Vision base behavioral neurology career disease diagnosis distinguished professor improved individual patient innovation model development motor disorder neuroimaging professor protein misfolding prototype skills statistics technology training therapy design tool treatment strategy user friendly software user-friendly

项目摘要

Huntington's disease (HD) is a progressive, neurodegenerative disorder that can be genetically diagnosed years before clinical symptoms onset. This presents groundbreaking opportunities to learn the overall, dynamic progression of HD which is critical to the timing of therapeutic interventions and design of effective clinical trials. Despite advancements in this area, signiﬁcant gaps exist about the transitional period from premanifest to mani- 7. Project Summary/Abstract fest HD, particularly how and when overt clinical symptoms and neurological deterioration develop. As part of the candidate's long-term goal to become an independent, lead expert biostatistician for neurodegenerative diseases, the overarching goal of this K01 is to acquire training in the disease-related background and quantitative analyti- cal skills to develop innovative methods that target new discoveries of HD progression. The candidate, Dr. Tanya P. Garcia, is a Huntington's Disease Society of America (HDSA) Human Biology Project Fellow (2013-2015) and has assembled a team of outstanding mentors and collaborators who will provide training to acquire the skills she lacks for an independent, biostatistically-focused, neuroscience career. Her two primary mentors are Dr. Karen Marder and Dr. Raymond J. Carroll. Dr. Marder is the Sally Kerlin Professor of Neurology at Columbia University with over 300 publications in behavioral neurology, neuroepidemiology and neurodegenerative diseases including Huntington's, Alzheimer's, Parkinson's and HIV dementia. Dr. Carroll is Distinguished Professor of Statistics at Texas A&M University with over 400 publications and 5 books in multiple statistics areas, particularly in those needed for this proposal. To conduct high-level research that ﬁlls signiﬁcant gaps about HD progression knowl- edge, Dr. Garcia proposes in-depth training (i) To learn the latest developments and challenges in clinical and neurological understanding of HD to ﬁne-tune statistical methodology; (ii) To obtain proﬁciency in analysis of cor- related, longitudinal, big data; and (iii) To develop programming expertise to make the proposed methods acces- sible to neuroscience investigators in user-friendly software. Training in these areas directly support Dr. Garcia's research aims which are (i) To improve prediction of HD motor-diagnosis by modeling the time-varying effects of multiple clinical performance measures; (ii) To improve identiﬁcation of disease-relevant brain regions in relation to HD motor-diagnosis by modeling the spatial-temporal brain structure; and (iii) To develop the ﬁrst generation of a HD Progression Risk Assessment Tool (HD-PRAT). Expected research outcomes include models that support President Obama's Precision Medicine Initiative in that they adhere to “2P's” of the NIH New Strategic Vision of the “4P's” of Medicine: they will offer promising ways to Predict the pattern and intensity of an individual's clinical and neurological changes over time; and increase the capacity to Personalize early intervention based on these learned predictions. Having the models available in user-friendly HD-PRAT is of high

亨廷顿舞蹈症 (HD) 是一种进行性神经退行性疾病，可通过基因诊断这为了解整体、动态的情况提供了开创性的机会。 HD 的进展对于治疗干预的时机和有效临床试验的设计至关重要。尽管在这一领域取得了进展，但从预清单到清单的过渡期仍存在显着差距。 7. 项目总结/摘要 HD，特别是如何以及何时出现明显的临床症状和神经功能恶化。候选人的长期目标是成为神经退行性疾病的独立首席专家生物统计学家， K01 的总体目标是获得疾病相关背景和定量分析方面的培训候选人 Tanya 博士开发针对 HD 进展新发现的创新方法。 P. Garcia，美国亨廷顿病协会 (HDSA) 人类生物学项目研究员（2013-2015）组建了一支由杰出导师和合作者组成的团队，他们将提供培训以获取她所掌握的技能她缺乏独立的、以生物统计学为重点的神经科学职业，她的两位主要导师是凯伦博士。 Marder 和 Raymond J. Carroll 博士 Marder 博士是哥伦比亚大学神经学教授 Sally Kerlin。在行为神经学、神经流行病学和神经退行性疾病方面发表了 300 多篇出版物，包括卡罗尔博士是亨廷顿舞蹈症、阿尔茨海默病、帕金森病和艾滋病痴呆症的杰出统计学教授。德克萨斯 A&M 大学在多个统计领域拥有 400 多种出版物和 5 本书，特别是在该提案需要进行高水平的研究，以填补 HD 进展知识的重大空白。 Garcia博士提出深入培训（i）了解临床和临床领域的最新发展和挑战对 HD 的神经学理解，以微调统计方法；(ii) 熟练地分析相关因素；相关的、纵向的、大数据；以及（iii）开发编程专业知识以使所提出的方法能够访问神经科学研究人员可以使用用户友好的软件来直接支持加西亚博士的培训。研究目标是 (i) 通过对运动的时变效应进行建模来改进 HD 运动诊断的预测多种临床表现测量；（ii）改善疾病相关大脑区域的识别通过模拟时空大脑结构进行高清运动诊断；以及 (iii) 开发第一代 HD 进展风险评估工具 (HD-PRAT) 的预期研究成果包括支持模型。奥巴马总统的精准医疗计划，坚持 NIH 新战略愿景的“2P” 医学的“4P”：它们将提供有前途的方法来预测个人临床的模式和强度以及随着时间的推移神经系统的变化；并提高基于这些的个性化早期干预的能力在用户友好的 HD-PRAT 中提供模型是非常重要的。