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.

抽象的脑白质营养不良是一种罕见的遗传性疾病，由于脑白质缺失或缺失而影响大脑白质。缺乏髓磷脂，髓磷脂是神经系统中隔离轴突的脂质膜。尽管截然不同分子病因学、类似的功能障碍在这些疾病中很常见，并且通常似乎与疾病进展相关。然而，临床结果评估（COA）严重缺乏，可用于临床试验的经过验证的工具很少。该提案将推进通过创建试验就绪工具箱和多中心数据，为脑白质营养不良的临床试验做好准备集成系统。此外，该项目将通过以下方式促进脑白质营养不良界的持续努力：汇集了十多个患者倡导团体、行业利益相关者和两个预现有脑白质营养不良联盟。使用这个框架，我们将评估现有临床的有效性脑白质营养不良的结果评估工具（目标 1）。我们还将部署患者报告的结果更好地了解脑白质营养不良进展的措施（目标 2）。最后我们将部署利用电子病历（EMR）的综合技术来识别和分类自然历史数据有助于形成数据驱动的脑白质营养不良表型（目标 3）。方法论将经历面部验证、评估者间可靠性、再现性、纵向稳定性、内部验证和构建在我们的数据集成核心和倡导合作伙伴的仔细监督下的有效性。我们预期的影响是定义了解脑白质营养不良患者自然史的最佳工具。这纵向研究将提供大量数据和管理方法，为我们提供信息并赋予我们权力科学、宣传和商业利益相关者的配套项目和未来目标脑白质营养不良。