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，由于脑白质缺失或缺失而影响脑白质。 缺少髓鞘，这是一种隔绝神经系统轴突的脂膜。尽管完全不同 分子病因，类似的功能障碍在这些疾病中很常见，通常 似乎与疾病的进展有关。然而，临床结果评估(COA)是 严重缺乏，几乎没有经过验证的工具可用于临床试验。这项提议将会取得进展 通过建立试验准备工具箱和多中心数据对脑白质营养不良的临床试验准备情况 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正在进行的努力 汇集了十多个患者权益倡导团体、行业利益相关者和两个预 现有的脑白质营养不良联盟。利用这个框架，我们将评估现有临床试验的有效性。 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)进行自然识别和分类的综合技术 有助于脑白质营养不良的数据驱动表型的病史数据(目标3)。方法论将经历 面向验证、评分者之间的可靠性、重复性、纵向稳定性、内部验证和结构 在我们的数据整合核心和倡导合作伙伴的仔细监督下，我们将确保数据的有效性。我们期待的 Impact是定义了解脑白质营养不良患者自然病史的最佳工具。这 纵向研究将提供大量数据和管理方法，这些数据和管理方法将为我们的 伙伴项目和科学、宣传和商业利益攸关方在 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.