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: 7783095
• 负责人: Michael P McDermott
• 金额: $ 90.26万
• 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/7783095
• 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; Clinical Trials Design; 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; Muscular Dystrophies; 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）：本申请要求为国际多中心临床试验提供资金，以比较三种不同的皮质类固醇（CS）方案，以治疗Duchenne肌肉营养不良（DMD）。这是来自纽卡斯尔大学（英国）的凯特·布什比（Kate Bushby）的同伴申请。该项目的主要目的是进行国际多中心，随机，双盲，对照试验，其中300名DMD在4至7岁之间的儿童将被随机分配以接收每日泼尼松（0.75 mg/kg）（0.75 mg/kg）（每日deflazacort），每天的deflazacort（0.90 mg/kg），或0.90 mg/kg），或者（10天）（10天），kg/kg。三年。主要结果变量将是三维的，包括（1）躺着的时间（对数转换），（2）强迫生命力和（3）受试者/父母全球对治疗的满意度，在三年的随访期内所有基本后的访问中均平均。该试验将解决务实的假设，即每天的泼尼松和每日Deflazacort在功能和主题/父母满意度方面将比在三年期间给出的间歇性CS（泼尼松）更大。 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网络/数据库环境； （2）为该试验提供生物统计学支持，包括：统计分析计划的改进和实施，以解决试验的具体目标；设计和实施一项临时监测计划，该计划将根据早期的安全问题进行修改或终止研究，并结合NINDS任命的数据和安全监控委员会（DSMB）；并准备DSMB的开放和闭幕报告。 公共卫生相关性：该试验是专门设计的，目的是解决已提出的问题，因为它是建立Duchenne肌肉营养不良（DMD）实践标准的临床相关障碍，即缺乏有关不同皮质类固醇治疗方案的相对功效和风险的指导，尤其是缺乏长期数据。当前的试验将对DMD中使用皮质类固醇的使用立即转移到诊所中生成实用指导。