Clinic-based Multicenter ALS Natural History Data Collection

项目概要/摘要 肌萎缩侧索硬化症（ALS）是一种普遍致残和致命的神经系统疾病。 目前的治疗方法只有适度的益处。开发有效的治疗方法是 部分原因是对ALS自然史的了解不足。虽然很有价值， ALS登记研究的样本量较大，但临床信息有限， ALS人群的小子集，或提供相对较短时期的信息。 然而，作为常规临床护理的一部分，ALS多学科诊所（MDC）开发了丰富的 来自所有ALS患者的自然史数据集，大多数ALS患者在 MDCs。我们已经从1,700多个ALS中建立了一个组合的，去识别的自然历史数据集 来自9个MDC的患者，种族代表性反映了整个ALS人群 以及广泛的地域代表性。我们为所有在我们诊所就诊的患者提供登记。 我们将在我们的多中心，纵向，前瞻性MDC数据集的基础上，与 行业和ALS患者社区提供临床试验的关键信息 开发和上市后评价。具体来说，我们将做以下工作： 临床相关的基线特征和血清神经丝光（NfL）测量， 入组以及经验证的疾病进展纵向指标，包括 ALSFRS-R与疾病分期、呼吸肺活量、说话率和10米步行试验 (Aim 1）根据患者报告的结局记录疾病里程碑， 电子健康记录中的设备订单，以及其他事件，如 胃造口术、住院和死亡（目标2），以及使用基线的至事件时间模型 特征以及回顾性和前瞻性纵向数据（目标3）。我们有 证明了有能力招募绝大多数在我们诊所寻求治疗的患者， 最能代表ALS人群基线特征将包括ALS表型和 基因检测的结果。数据集将提供给学术界和工业界 研究人员推进ALS护理，药物开发和结果研究。我们将扩大 业界和其他利益攸关方的现有参与，包括一个咨询小组， ALS患者，并将鼓励通过这些数据传播的机会 现有的关系和出版物。

Project summary/abstract Amyotrophic lateral sclerosis (ALS) is a universally disabling and fatal neurological condition. Current treatments have only modest benefit. Development of effective therapeutics is hampered in part by inadequate knowledge of ALS natural history. Though valuable, existing ALS registries have either large samples sizes but limited clinical information, focus on relatively small subsets of the ALS population, or provide information from a relatively brief period. However, as a part of routine clinical care, ALS multidisciplinary clinics (MDCs) develop a rich natural history dataset from all ALS patients, and most people living with ALS are seen at MDCs. We have built a combined, de-identified natural history dataset from over 1,700 ALS patients from 9 MDCs, with racial representation that is reflective of the ALS population at large and broad geographic representation as well. We offer enrollment to all patients at our clinics. We will build on our multicenter, longitudinal, prospective MDC dataset in collaboration with industry and the ALS patient community to provide information critical for clinical trial development and post-marketing evaluation. Specifically, we will do the following: record clinically relevant baseline characteristics and serum neurofilament light (NfL) measurements at enrollment as well as validated longitudinal measures of disease progression including ALSFRS-R and disease staging, respiratory vital capacity, speaking rate and 10 meter walk test (Aim 1), record disease milestones based upon patient-reported outcomes, durable medical equipment orders in the electronic health record, and other events such as dates of gastrostomy, hospitalizations, and death (Aim 2), and model time to events using baseline characteristics as well as retrospective and prospective longitudinal data (Aim 3). We have demonstrated the ability to enroll the vast majority of patients seeking care in our clinics so as to best represent the ALS population. Baseline characteristics will include ALS phenotype and results of genetic testing. Datasets will be made available to academic and industry investigators to advance ALS care, drug development, and outcomes research. We will expand existing engagement from industry and other stakeholders to include an advisory panel of people living with ALS and will encourage opportunities for data dissemination through these existing relationships and publications.