Biostatistics and Data Management for a Trial of Corticosteroid Regimens in DMD

描述(申请人提供)：本申请申请资助一项国际多中心临床试验的数据管理和生物统计学支持，该试验比较了三种不同的皮质类固醇(CS)方案治疗Duchenne肌营养不良症(DMD)。这是英国纽卡斯尔大学医学博士凯特·布什比和美国罗切斯特大学医学博士罗伯特·C·格里格斯提出的题为“FOR-DMD：优化Duchenne MD类固醇疗法的双盲随机试验”的配套申请。该项目的主要目标是进行一项国际多中心、随机、双盲、对照试验，将300名4至7岁的DMD儿童随机分为三组，分别接受每日泼尼松(0.75 mg/kg)、每日呋喃西林(0.90 mg/kg)或间歇性(开始10天，休息10天)强的松(0.75 mg/kg)，并进行至少三年的随访。主要结果变量将是三维的，并将包括(1)从卧床站立的时间(对数转换)，(2)用力肺活量，以及(3)受试者/父母对治疗的总体满意度，所有这些都是在三年随访期内所有基线后就诊的平均结果。这项试验将解决一个务实的假设，即在功能和对象/父母满意度方面，每天服用泼尼松和每天服用地塞米松将比在三年内间歇服用CS(泼尼松)更有好处。我们申请的具体目的是(1)为试验提供数据管理，包括：制定和实施基于网络的随机和登记程序，提供电子病例报告表格，通过互联网便利将所有研究数据输入标准化关系数据库，培训现场人员使用基于网络的应用程序进行随机化和数据输入，生成和解决数据查询，监测重要研究事件，以及维护适当安全和合规的网络/数据库环境；(2)为试验提供生物统计学支持，包括：完善和实施统计分析计划，以满足试验的具体目标；与NINDS指定的数据和安全监测委员会(数据和安全监测委员会)一起，设计和实施一项临时监测计划，以便能够根据安全问题的早期证据修改或终止这项研究；并为数据和安全监测委员会编写公开和非公开会议报告。

DESCRIPTION (provided by applicant): This application requests funding for the data management and biostatistical support for an international multicenter clinical trial comparing three different corticosteroid (CS) regimens for the treatment of Duchenne muscular dystrophy (DMD). This is a companion application to that of Kate Bushby, M.D. from the University of Newcastle (UK) and Robert C. Griggs, M.D. from the University of Rochester (USA) entitled "FOR-DMD: Double-Blind Randomized Trial to Optimize Steroid Regimens in Duchenne MD." The primary aim of this project is to conduct an international multicenter, randomized, double-blind, controlled trial in which 300 children with DMD between the ages of 4 and 7 will be randomized to receive either daily prednisone (0.75 mg/kg), daily deflazacort (0.90 mg/kg), or intermittent (10 days on, 10 days off) prednisone (0.75 mg/kg) and followed for a minimum of three years. The primary outcome variable will be three-dimensional and will consist of (1) time to stand from lying (log-transformed), (2) forced vital capacity, and (3) subject/parent global satisfaction with treatment, all averaged over all post-baseline visits during the three-year follow-up period. The trial will address the pragmatic hypothesis that daily prednisone and daily deflazacort will be of greater benefit in terms of function and subject/parent satisfaction than intermittent CS (prednisone) given over a three-year period. The specific aims of our application are (1) To provide data management for the trial including: development and implementation of web-based randomization and enrollment procedures, provision of electronic case report forms, internet-facilitated entry of all study data into a standardized relational database, training of site personnel in the use of web-based applications for randomization and data entry, generation and resolution of data queries, monitoring of important study events, and maintenance of an appropriately secured and compliant network/database environment; and (2) To provide biostatistical support for the trial including: refinement and implementation of the statistical analysis plan to address the specific aims of the trial; design and implementation of an interim monitoring plan that will allow modification or termination of the study on the basis of early evidence of safety concerns, in conjunction with the NINDS-appointed Data and Safety Monitoring Board (DSMB); and preparation of open- and closed-session reports for the DSMB.