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

DMD 皮质类固醇治疗方案试验的生物统计学和数据管理

• 批准号: 8100213
• 负责人: Michael P McDermott
• 金额: $ 57.33万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100213
• 关键词: 7 year old; Address; Adrenal Cortex Hormones; Adverse event; Age; Biometry; Case Report Form; Child; Clinic; Clinical Trials; Clinical Trials Data Monitoring Committees; Companions; Computational Biology; Country; Data; Databases; Development; Disclosure; Doctor of Medicine; Double-Blind Method; Duchenne muscular dystrophy; Electronics; Emergency treatment; Enrollment; Environment; Event; Funding; Future; Generations; Heart Research; Heterogeneity; Human Resources; International; Internet; Licensing; Maintenance; Measures; Medical center; Modification; Monitor; Muscle; National Institute of Neurological Disorders and Stroke; Neurology; Neuromuscular Diseases; Online Systems; Outcome; Parents; Patients; Pharmaceutical Preparations; Prednisone; Preparation; Procedures; Questionnaires; Randomized; Regimen; Relative (related person); Reporting; Request for Applications; Research; Research Infrastructure; Resolution; Risk; Safety; Sample Size; Screening procedure; Secure; Serious Adverse Event; Site; Steroids; Suspension substance; Suspensions; System; Technology; Testing; Time; Training; Treatment Protocols; Universities; Visit; Vital capacity; Withdrawal; base; clinical practice; clinically relevant; clinically significant; control trial; data management; deflazacort; design; dosage; evidence base; follow-up; premature; primary outcome; programs; public health relevance; randomized trial; relational database; satisfaction; statistics; trial comparing

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.

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。这是英国纽卡斯尔大学凯特·布什比医学博士和美国罗切斯特大学罗伯特·C·格里格斯医学博士题为“FOR-DMD：优化 Duchenne MD 类固醇治疗方案的双盲随机试验”的配套申请。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 岁至 7 岁之间患有 DMD 的儿童将随机接受每日泼尼松 (0.75 mg/kg)、每日地夫可特 (0.90 mg/kg) 或间歇性（10 天，休息 10 天）泼尼松 (0.75 mg/kg) 治疗，并随访至少 三年。主要结果变量将是三维的，包括（1）从说谎起立的时间（对数转换），（2）用力肺活量，以及（3）受试者/家长对治疗的整体满意度，所有这些都是三年随访期间所有基线后访视的平均值。该试验将提出一个务实的假设，即每日泼尼松和每日地夫可特在功能和受试者/家长满意度方面比三年期间给予间歇性 CS（泼尼松）具有更大的益处。我们应用程序的具体目标是（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，通过互联网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，监控重要的研究事件以及维护适当的安全和合规性 网络/数据库环境； (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，以实现试验的具体目标；与 NINDS 指定的数据和安全监测委员会 (DSMB) 一起设计和实施临时监测计划，该计划将允许根据安全问题的早期证据修改或终止研究；为 DSMB 准备公开会议和闭门会议报告。 公众健康相关性：本试验专门用于解决杜氏肌营养不良症 (DMD) 实践标准的临床相关障碍问题，即缺乏对不同皮质类固醇治疗方案的相对疗效和风险的指导，特别是缺乏长期数据。目前的试验将为 DMD 中使用皮质类固醇提供实用指导，以便立即转移到临床。