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，该试验比较了治疗杜氏肌营养不良症（DMD）的三种不同皮质类固醇（CS）方案。这是Kate Bushby医学博士的配套应用程序。来自英国纽卡斯尔大学的Robert C.格里格斯，医学博士来自罗切斯特大学（美国）的题为“FOR-DMD：在Duchenne MD优化类固醇方案的双盲随机试验。“该项目的主要目的是进行一项国际多中心、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泼尼松或（0.75 mg/kg）、每日地夫可特（0.90 mg/kg）或间歇性（给药10天，停药10天）泼尼松（0.75 mg/kg），并随访至少三年。主要结局变量将是三维的，包括（1）从躺下站立的时间（对数转换），（2）用力肺活量，和（3）受试者/父母对治疗的总体满意度，均为3年随访期间所有基线后访视的平均值。该试验将解决一个实用的假设，即每日泼尼松和每日地夫可特在功能和受试者/家长满意度方面比间歇性CS（泼尼松）在三年内给药的获益更大。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入组程序，提供电子病例报告表，通过互联网将所有研究数据输入标准化关系数据库，培训研究中心工作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，并维护适当安全和合规的网络/数据库环境;以及（2）为试验提供生物统计支持，包括：完善和实施统计分析计划，以实现试验的特定目标;设计和实施中期监查计划，允许根据以下早期证据修改或终止研究：与NINDS指定的数据和安全性监测委员会（DSMB）合作，解决安全性问题;并为DSMB编写公开和非公开会议报告。 公共卫生相关性：这项试验是专门设计来解决已提出的问题，作为临床相关的障碍，建立标准的实践杜氏肌营养不良症（DMD），即缺乏指导的相对疗效和风险的不同皮质类固醇方案，特别是缺乏长期的数据。目前的试验将产生实用的指导使用糖皮质激素的DMD立即转移到诊所。

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.