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

描述（由申请人提供）：本申请要求为一项比较三种不同皮质类固醇（CS）治疗杜氏肌营养不良症（DMD）的国际多中心临床试验的数据管理和生物统计学支持提供资金。这是英国纽卡斯尔大学的凯特·布什比博士和美国罗切斯特大学的罗伯特·c·格里格斯博士的配套申请，题为“FOR-DMD：“该项目的主要目的是开展一项国际多中心，随机，双盲，对照试验，其中300名4至7岁的DMD儿童将随机接受每日强的松（0.75 mg/kg），每日地扎柯（0.90 mg/kg）或间歇性（10天使用，10天休息）强的松（0.75 mg/kg），并至少随访三年。主要结果变量将是三维的，将包括(1)站立时间（对数变换），(2)强制肺活量，(3)受试者/家长对治疗的总体满意度，所有这些都是在三年随访期间基线后所有就诊的平均值。该试验将解决实用性假设，即在功能和受试者/家长满意度方面，每日强的松和每日地帕沙柯比间歇性CS（强的松）给予三年时间更大的益处。我们申请的具体目的是：(1)为试验提供数据管理，包括：开发和实施基于网络的随机化和登记程序，提供电子病例报告表格，在互联网上方便地将所有研究数据输入标准化的关系数据库，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，监测重要的研究事件，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：细化和实施统计分析计划，以满足试验的具体目标；设计和实施一项临时监测计划，以便与国家原子能和科学研究院指定的数据和安全监测委员会（DSMB）合作，根据安全问题的早期证据修改或终止研究；以及为资管局编写公开会议和闭会报告。

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. PUBLIC HEALTH RELEVANCE: This trial is specifically designed to address the problems that have been raised as clinically relevant obstacles to establishing standards of practice in Duchenne muscular dystrophy (DMD), namely the lack of guidance on the relative efficacy and risks of different corticosteroid regimens and, in particular, the lack of long-term data. The current trial will generate practical guidance on the use of corticosteroids in DMD for immediate transfer into the clinic.