Parkinson's Disease Clinical Trial: Statistical Center

描述（由申请人提供）：神经科学界的一个主要目标是制定治疗策略，以减缓或预防帕金森病（PD）的进展。PD是最常见的成人神经退行性疾病之一，在北美和欧盟影响超过100万人。作为第一步，基于无效研究，NINDS帕金森病探索性试验（NET-PD）网络确定肌酸是减缓帕金森病临床衰退的潜在药物。NET-PD网络目前正在进行一项比较肌酸和安慰剂的大型长期III期试验（LS-1）。在更新期间，统计协调中心（SCC）建议与临床协调中心（CCC）和临床站点一起完成以下具体目标，以继续和完成LS1：目的1在多巴胺能治疗和最佳PD护理的背景下，在基线和5年随访期间，每日给予肌酸（10gm/天）比安慰剂更有效地减缓PD的临床下降。鉴于帕金森病是一种多因素疾病，可导致认知、运动和行为障碍，因此采用Global Statistical Test分析临床衰退的全局结果测量，以提供检测疾病状态细微总体变化的敏感性；目的2：测试一组次要假设，以提供对主要结果的见解；目标3继续担任SCC和(a)为CCC准备关于临床站点表现的中期报告，包括保留，患者安全性（盲法）和数据质量；(b)参与解决留用问题；目标4继续(a)在整个项目期间尽量减少偏见和保护盲法，(b)根据需要对与有效性和安全性相关的结果措施进行裁决，以及(c)向数据和安全监测委员会（DSMB）提供定期报告和中期分析；目标5：与CCC和临床站点合作(a)解释和报告结果，(b)将数据记录并存档到一个公开的数据库中。目标6：维持一个允许与CCC、临床中心、NINDS科学计划人员、DSMB和NIH监督委员会密切合作的行政结构。

DESCRIPTION (provided by applicant): A major goal of the neuroscience community is to develop treatment strategies that will slow or forestall the progression of Parkinson's disease (PD). PD is one of the most common adult neurodegenerative disorders, affecting over 1 million people in North America and the European Union. As a first step, based on futility studies, the NINDS Exploratory Trials in Parkinson's disease (NET-PD) network identified creatine as a potential agent to slow clinical decline in PD. The NET-PD network is now conducting a large long term Phase III trial (LS-1) comparing creatine to placebo. During the renewal period the Statistical Coordination Center (SCC) proposes to complete the following specific aims in conjunction with the Clinical Coordination Center (CCC) and Clinical Sites in order to continue and complete LS1: Aim1 Test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. Given that PD is a multi-factorial disease that contributes to cognitive, motor, and behavioral disability, a gloal outcome measure of clinical decline analyzed by Global Statistical Test is utilized to provide sensitivity in detecting subtle overall changes in disease state; Aim 2 Test a set of secondary hypotheses to provide insight into the primary results; Aim 3 Continue as the SCC and (a) prepare interim reports for the CCC on performance of the Clinical Sites including retention, patient safety (blinded), and data quality; and (b) participate in the solution of problems with retention; Aim 4 Continue to (a) minimize bias and protect blinding during the entire project, (b) adjudicate outcome measures relating to efficacy and safety (as needed), and (c) provide periodic reports and interim analyses to the Data and Safety Monitoring Board (DSMB); Aim 5 In collaboration with the CCC and Clinical Sites (a) interpret and report results, and (b) document and archive the data in a publically available database. Aim 6 Maintain an administrative structure that allows close collaboration with the CCC, the clinical centers, NINDS Scientific Program personnel, the DSMB, and the NIH Oversight Board.