Vasculitis Outcome Measures: Development and Validation

描述(由申请人提供)： 缺乏严格验证的结果衡量标准仍然是许多形式的系统性脉管炎优秀临床试验表现的重大障碍。在这项提案中，国际系统性脉管炎研究网络(INSSYS)和脉管炎临床研究联盟(VCRC)的领导人将建立在其联合研究小组富有成效的合作基础上。调查人员还将利用由合作伙伴约翰·斯通博士和彼得·默克尔带头的资助研究计划提供的资源。有两个具体目标： 目的1：建立和验证ANCA相关性小血管炎的共识疾病活动性测量方法。这一新的共识结果指标(“Canvas”)将在定于美国和欧洲开始的临床试验中得到验证。这一目标的结果还将为确定疾病活动的三种临界状态提供基础：缓解、病情暴发和稳定/持续疾病。这些定义对于确定部分缓解和完全缓解这样的中心临床试验结果至关重要。 目的：建立磁共振成像(MR)和正电子发射断层扫描(PET)作为大血管炎的临床试验结果指标。这一目标将通过风湿科医生、放射科医生、统计学家和生物信息学家合作对患者进行数据驱动的评估来实现。该项目利用了这些互补成像模式的进展，这些成像模式提供了关于血管管腔狭窄和血管壁内生物炎症状态的信息。 这两个项目都涉及来自美国和欧洲的脉管炎研究和临床试验的领导者。临床脉管炎研究人员由一组在结果测量开发方面拥有丰富经验并拥有其他相关技能的专家作为补充。

DESCRIPTION (provided by applicant): The lack of rigorously-validated outcome measures remains a substantial hurdle to the performance of excellent clinical trials in many forms of systemic vasculitis. In this proposal, leaders of the International Network for the Study of the Systemic Vasculitides (INSSYS) and the Vasculitis Clinical Research Consortium (VCRC) will build upon the productive Collaborations of their combined Research Groups. The investigators will also leverage the resources provided by funded research initiatives spearheaded by the Co-P.I.s, Drs. John Stone and Peter Merkel. There are two Specific Aims: Aim 1: To develop and validate a consensus disease activity measure for ANCA-associated vasculitis. This new consensus outcome measure ("CANVAS") will be validated in clinical trials slated to begin in both the United States and Europe. The results of this Aim will also provide a basis for defining three critical states of disease activity: remission, flare, and stable/persistent disease. These definitions are crucial to identifying such central clinical trials outcomes as partial responses and complete remissions. Aim 2: To develop magnetic resonance (MR) imaging and positron emission tomography (PET) as clinical trial outcome measures in large vessel vasculitis. This Aim will be achieved through data-driven assessments of patients involving a collaboration of rheumatologists, radiologists, statisticians, and bioinformaticists. The project capitalizes upon advances in these complementary imaging modalities that provide information about both narrowing of the vessel lumen and the state of biological inflammation within the blood vessel wall. Both projects involve leaders in vasculitis research and clinical trials from the United States and Europe. The clinical vasculitis investigators are supplemented by a group of experts who have extensive experience in outcome measures development and possess other pertinent skills.