Efficacy Measures for Pediatric Lupus Studies

研究概述：儿童期发作的系统性红斑狼疮（cSLE）是一种严重的自身免疫性疾病， 迫切需要更好的药物来降低其死亡率。有一个根本的差距， 了解如何全面衡量cSLE的临床相关变化是否 发生了。这使得新药的测试非常困难。我们研究的长期目标是提高 通过制定和传播有助于cSLE预后的结局指标， 生物标志物的发现，促进转化研究，并进行临床试验，以测试疗效 cSLE新药本申请的目的是前瞻性验证疾病发作的标准， o制定疾病缓解标准，同时建立共同的电子数据管理框架- 为将来的cSLE研究工作。待检验的中心假设是cSLE核心集变量（疾病 活动性，疾病活动性的MD评级，健康、身体功能、蛋白尿、损伤的患者评级， 生长和发育）最适合定义cSLE中的疾病发作，并且相同的cSLE核心集 变量可用于开发缓解标准。我们建议测试中心假设，并实现 通过追求以下具体目标来实现研究目标：1）制定并前瞻性验证标准 通过共识形成方法和统计方法的结合， 美国流变学学会质量测量委员会推荐2）建立一个 hildhood关节炎流变学研究联盟（CARRA）儿科狼疮登记处的目标是 制定cSLE疾病缓解的初步标准。实现这些目标的方法是使用 来自定义明确的已建立队列的数据和新收集的100例极端高血压患者的信息 cSLE表型，以获得关于发作、缓解和相关疾病的发生的真实患者信息。 cSLE核心变量的变化（> 750患者-年随访; n> 400）。与以下机构密切合作： 通过使用共识方法（德尔菲，名义组技术），数据挖掘 技术和其他统计方法定量验证耀斑的标准和初步标准， 疾病将得到缓解。我们将为此改进基于网络的数据管理系统 study.在NIH资助的卓越中心和CCHMC流变学临床试验单位的支持下， 该应用的预期结果是可以容易地用作有效性测量的耀斑标准， cSLE临床试验和cSLE缓解的初步标准。收集的数据将作为 CARRA儿童狼疮登记处和基于网络的多功能狼疮研究管理的基础 系统将被开发并提供给儿科风湿病社区。这是少校的 重要性，因为定量验证的爆发标准将促进疾病改变的临床试验 药物，而缓解标准是至关重要的，以测试最有效的新药物，目前正在 开发基于网络的学习管理节省了成本和时间，促进了未来的合作研究。 与公共卫生的相关性：正如最近出版的NIAMS长期 研究计划，并通过利用NIH资助的卓越中心的专业知识，拟议的研究 将加强生物医学和临床研究人员的"工具箱"，并作为提高质量的场所 通过开发更好的药物来改善儿童cSLE的生活和预后。

'ROJECT SUMMARY: Childhood-onset Systemic Lupus Erythematosus (cSLE) is a severe autoimmune disease and better medications are urgently needed to decrease its mortality. There is a fundamental gap in he knowledge of how to comprehensively measure whether clinically relevant changes in cSLE have occurred. This makes the testing of new drugs very difficult. The long-term goal of our research is to improve he prognosis of cSLE through the development and dissemination of outcome measures that will facilitate biomarker discovery, promote translational research, and the conduct of clinical trials to test the efficacy of new cSLE drugs. The objectives of this application are to prospectively validate criteria of disease flare and o develop criteria of disease remission, while establishing a common electronic data management frame- work for future cSLE studies. The central hypothesis to be tested is that the cSLE core set variables (disease activity, MD rating of disease activity, patient rating of well-being, physical function, proteinuria, damage, growth & development) are best suited to define disease flares in cSLE and that the same cSLE core set variables can be used to develop remission criteria. We propose to test the central hypothesis and achieve he study objectives by pursuing the following specific aims: 1) To develop and prospectively validate criteria of disease flare by a combination of consensus formation methodology and statistical approaches as is recommended by the American College of Rheumatology Committee on Quality Measures 2) To establish a "hildhood Arthritis Rheumatology Research Alliance (CARRA) Pediatric Lupus Registry with the goal of develop preliminary criteria of disease remission in cSLE. The approach to achieving these aims is to use data from well-defined established cohorts and newly collected information of 100 patients with extreme cSLE phenotypes to obtain real-patient information on the occurrence of flares, remission and the related changes in the cSLE core variables (>750 patient-years of follow-up; n>400). In close collaborations with Drofessional societies and by using consensus methodology (Delphi, nominal group technique), data mining techniques, and other statistical approaches quantitatively validated criteria of flare and preliminary criteria of disease remission will be developed. Our web-based data management systems will be improved for this study. Supported by NIH-funded Centers of Excellence and the CCHMC Rheumatology Clinical Trial Unit, the expected results of this application are flare criteria that can readily be used as efficacy measures of clinical trials in cSLE and preliminary criteria of remission for cSLE. The collected data will serve as the foundation for a CARRA Pediatric Lupus Registry, and a versatile web-based Lupus Study Management System will be developed and made available to the pediatric rheumatology community. This is of major significance because quantitatively validated flare criteria will facilitate clinical trials of disease modifying drugs, while remission criteria are critical to test the most potent new medications that are currently being developed. Web-based study management is cost & time saving and promotes future collaborative research. RELEVANCE TO PUBLIC HEALTH: As is suggested by the recently published NIAMS Long-Term Research Plan and by leveraging the expertise of NIH-funded Centers of Excellence, the proposed research will enhance the "tool box" of biomedical & clinical investigators and serve as a venue to improve the quality of life and prognosis of children with cSLE through the development of better drugs.