Clinic-based Multicenter ALS Natural History Data Collection

项目摘要/摘要 肌萎缩侧索硬化症(ALS)是一种普遍的致残性和致命性神经系统疾病。 目前的治疗方法只有很小的好处。有效疗法的发展是 这在一定程度上受到了对肌萎缩侧索硬化症自然史知识不足的阻碍。虽然有价值，但已经存在 ALS登记的样本量大，但临床信息有限，集中在相对 ALS人群的一小部分，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)发展了丰富的 所有肌萎缩侧索硬化症患者的自然病史数据集，以及大多数患有肌萎缩侧索硬化症的人可以在 MDCS。我们已经从1700多个ALS中建立了一个合并的、未识别的自然历史数据集 来自9个疾病控制中心的患者，其种族代表性反映了ALS人群的总体情况 以及广泛的地理代表性。我们为我们诊所的所有患者提供注册。 我们将在我们的多中心、纵向、预期的MDC数据集的基础上与 行业和ALS患者社区提供对临床试验至关重要的信息 开发和上市后评估。具体来说，我们将做以下工作：记录 临床相关基线特征和血清神经细丝光(NFL)测量 登记以及经过验证的疾病进展的纵向测量，包括 ALSFRS-R与疾病分期、呼吸肺活量、语速和10米步行试验 (目标1)，根据患者报告的结果记录疾病里程碑，持久的医疗 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)，以及使用基线建立事件的模型时间 特点以及回顾和预期的纵向数据(目标3)。我们有 证明有能力招募绝大多数在我们诊所寻求护理的患者，以便 最好代表肌萎缩侧索硬化症人群。基线特征将包括ALS表型和 基因检测结果。数据集将向学术界和工业界提供 研究人员推进肌萎缩侧索硬化症治疗、药物开发和结果研究。我们将扩大规模 来自行业和其他利益相关者的现有参与，包括一个咨询小组 患有肌萎缩侧索硬化症的人，并将鼓励通过这些 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.