Optimizing Trial Readiness for Adrenomyeloneuropathy

摘要 脑白质营养不良是一种罕见的遗传性疾病，由于脑白色的丢失或缺失， 缺乏髓鞘，髓鞘是神经系统中隔离轴突的脂质膜。尽管不同的 分子病因学，类似的功能障碍在这些疾病中是常见的，并且通常 似乎与疾病进展有关。然而，临床结局评估（COA） 严重缺乏，很少有经过验证的工具可用于临床试验。该提案将推动 通过创建试验准备工具箱和多中心数据， 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社区的持续努力： 汇集了十几个患者倡导团体，行业利益相关者，以及两个预- 现有的脑白质营养不良财团。使用这个框架，我们将评估现有临床 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）识别和分类自然 有助于脑白质营养不良的数据驱动表型的历史数据（Aim 3）。方法论将经历 面效度、评分者间信度、可重复性、纵向稳定性、内部效度和结构 在我们的数据集成核心和倡导合作伙伴的仔细监督下，我们预期将面临 影响是定义最好的工具来了解脑白质营养不良个体的自然史。这 纵向研究将提供一套数据和管理方法， 科学、宣传和商业利益攸关方在《公约》方面的伙伴项目和未来目标 脑白质营养不良

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.