Optimizing Trial Readiness for Adrenomyeloneuropathy

优化肾上腺脊髓神经病的试验准备

基本信息

批准号：
10675464
负责人：
Adeline Lucie Vanderver
金额：
$ 63.72万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10675464
关键词：
Adrenomyeloneuropathy Adult Advocacy Affect Age Age of Onset Alexander Disease Algorithms Assessment tool Axon Brain Caregivers Categories Cessation of life Classification Clinical Clinical Trials Clinical Trials Network Code Communities Companions Computerized Medical Record Data Data Collection Diagnosis Disease Disease Progression Disparate Documentation Etiology Event Face Frequencies Future Genotype Goals Health Hereditary Disease Home Hospitalization Individual Industry Inpatients International Length Letters Link Longevity Longitudinal Studies Measures Medical Membrane Lipids Metachromatic Leukodystrophy Methodology Molecular Motor Myelin Natural History Nervous System Neurocognitive Newborn Infant Operative Surgical Procedures Outcome Outcome Assessment Outcome Measure Outpatients Patient Outcomes Assessments Patients Pelizaeus-Merzbacher Disease Performance Persons Phenotype Prospective Studies Provider Proxy Quality of life Records Reproducibility Schedule Secure Series Severities Site Standardization Surveys Systems Integration Technology Time Tube Validation Visit Woman World Health application programming interface clinical care clinical encounter clinical outcome assessment clinical trial readiness cohort data integration data mining disability discrete data empowerment experience feeding functional disability industry partner leukodystrophy men patient advocacy group prospective pseudotoxoplasmosis syndrome recruit remote assessment respiratory tool trial readiness white matter

项目摘要

Abstract Leukodystrophies are rare inherited diseases that affect the white matter of the brain due to the loss or absence of myelin, the lipid membrane that insulates axons in the nervous systems. Despite disparate molecular etiologies, similar functional impairments are common across these disorders and generally appear to associate with disease progression. Nevertheless, clinical outcome assessments (COA) are critically lacking, with very few validated tools available for use in clinical trials. This proposal will advance the clinical trial readiness of leukodystrophy by creating a trial-ready tool-box and multi-center data integration systems. Further, the project will catalyze ongoing efforts of the leukodystrophy community by bringing together more than a dozen patient advocacy groups, industry stakeholders, and two pre- existing leukodystrophy consortia. Using this framework, we will assess the validity of existing clinical outcome assessment tools in leukodystrophy (Aim 1). We will also deploy patient reported outcome measures to better understanding of the progression of leukodystrophies (Aim 2). Finally, we will deploy integrative technologies leveraging the electronic medical record (EMR) to identify and categorize natural history data contributing to a data-driven phenotype of leukodystrophies (Aim 3). Methodologies will undergo face validation, inter-rater reliability, reproducibility, longitudinal stability, internal validation and construct validity under the careful oversight of our data integration core and advocacy partners. Our anticipated impact is to define the best tools to understand natural history in individuals with leukodystrophy. This longitudinal study will provide a body of data and management approaches that will inform and empower our companion projects and future goals of the scientific, advocacy and commercial stakeholders in the leukodystrophies.

抽象的白细胞营养不良是罕见的遗传疾病，由于损失或缺乏髓磷脂，是神经系统中轴突绝缘的脂质膜。尽管不同分子病因，类似的功能障碍在这些疾病中很常见，而且通常似乎与疾病进展有关。然而，临床结果评估（COA）是严重缺乏，很少有经过验证的工具可用于临床试验。该提议将进步通过创建一个试用的工具箱和多中心数据，白细胞营养不良的临床试验准备就绪集成系统。此外，该项目将促进白细胞病社区正在进行的努力汇集了十几个患者倡导团体，行业利益相关者和两个预先的倡导者现有的白细胞营养财团。使用此框架，我们将评估现有临床的有效性白细胞营养不良中的结果评估工具（AIM 1）。我们还将部署患者报告的结果更好地理解白细胞营养不良的进展的措施（AIM 2）。最后，我们将部署利用电子病历（EMR）识别和分类自然的集成技术历史数据促进了白细胞营养不良的数据驱动表型（AIM 3）。方法将进行面对验证，评估者间的可靠性，可重复性，纵向稳定性，内部验证和构造在我们对数据集成核心和倡导伙伴的仔细监督下的有效性。我们的预期影响是定义了解白细胞营养不良患者自然史的最佳工具。这纵向研究将提供一系列数据和管理方法，以告知和授权我们的能力伴侣项目以及科学，倡导和商业利益相关者的未来目标白细胞营养不良。