ALS Clinical Trials Guidelines

 描述（申请人提供）：肌萎缩性侧索硬化症（ALS）是一种毁灭性的疾病，导致无情的渐进性骨骼肌麻痹和最终的呼吸衰竭;它总是导致大多数患者在3至5年内死亡。事实上，在过去的半个世纪里，已经进行了大约50项临床试验，利鲁唑的益处不大， 我们能开出的唯一ALS药物表明，在各个层面上，对ALS药物开发中采用的方法进行严格的重新评估是非常必要的。有效药物的必要性是紧迫的-ALS患者和那些照顾他们的人迫切需要新的治疗。创建先前ALS临床试验指南的会议于1998年举行，这些指南基于专家共识，于15年前的1999年出版，鉴于ALS临床试验的进展，新兴生物标志物和整体试验方法，使其完全过时。因此，我们建议召开一次重要的国际会议，审查ALS临床试验中的当前问题，并采用循证医学（EBM）方法制定新的和更新的ALS临床试验指南。我们的具体目标是：1。完成国际ALS医生和医生-科学家志愿者的组织委员会和咨询委员会的组建，以制定和组织一次国际会议，更新目前的ALS临床试验指南; 2.召开国际会议，回顾临床试验的问题和现状; 3.讨论并制定ALS随机对照试验的指导原则; 4.在主要神经病学期刊上发表指导原则，并促进这些指导原则在未来ALS试验中的实施。虽然我们提出了这个U13补助金，以支持年轻的临床试验和生物统计学家，基础科学家和药理学家在ALS的帮助下，额外的资金，我们计划有代表和参与所有ALS利益相关者，包括监管和资助机构的官员，临床试验，倡导团体，和患者及其护理人员。还将为那些不能亲自出席会议的人提供网络会议。我们相信，新的试验指南，当广泛传播和积极实施，将导致更有效和更高效的试验，导致更好的药物在未来的ALS的发展。

 DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is a devastating disease that causes relentlessly progressive skeletal muscle paralysis and eventual respiratory failure; it invariably leads to the death of most patients within 3 to 5 years. The fact that ~50 clinical trials have been performed in the past half-century and riluzole, with modest benefits, is the only ALS medication we can prescribe indicates a serious need for critical reassessment of the methods employed in ALS drug development at every level. The necessity for effective medications is urgent -- patients with ALS and those who care for them are desperate for new treatment. The meeting to create the previous ALS clinical trial guidelines was held in 1998, and these guidelines, based on expert consensus, were published 15 years ago in 1999, rendering them completely outdated in light of advances in clinical trials in ALS, emerging biomarkers, and overall trial methodology. Accordingly, we propose to hold a major international conference to review current issues in clinical trials in ALS and formulate new and updated ALS clinical trial guidelines using an evidence-based medicine (EBM) approach. We specifically aim: 1. To finalize the formation of an Organizing Committee and Advisory Board of international ALS physician and physician-scientist volunteers to develop and organize an international meeting that will update the present ALS clinical trial guidelines; 2. To hold an international conference o review the issues and current status of clinical trials; 3. To discuss and develop guidelines for ALS RCTs; and 4.To publish the guidelines in major neurology journals and promote implementation of these guidelines into future ALS trials. While we propose this U13 grant to support young clinical trialists and biostatisticians, basic scientists, and pharmacologists in ALS with the help of additional funding we plan to have representation and participation from all ALS stakeholders, including officers of regulatory and funding agencies, clinical trialists, advocacy groups, and patients and their caregivers. A web-conference will be also available for those who cannot attend the meeting in person. We believe that the new trial guidelines, when widely disseminated and actively implemented, will result in more effective and efficient trials, leading to the development of better medications in the future in ALS.