Provisional Combined Response Index For Patients With Diffuse Systemic Sclerosis

描述(由申请人提供)：系统性硬皮病(SSC)可与高发病率和死亡率有关。疾病的复杂性和异质性要求一个综合反应指数，该指数将涵盖不同的器官受累和患者报告的结果。迫切需要一个SSC综合反应指数(SSC-CRI)，以促进药物开发，并允许在SSC的临床试验之间进行比较，就像类风湿性关节炎中的类似指数一样。我们召集了一批国际专家，他们在不同关节炎的临床试验设计和反应标准制定方面拥有专业知识。加州大学洛杉矶分校临床协调中心成功协调了最近结束的由NIH资助的SSC临床试验。我们在开发SSC-CRI方面迈出了第一步，通过进行结构化的Delphi练习来开发用于临床试验的临时核心项目集。德尔福试验确定了11个与弥漫性SSC临床试验相关的领域。我们的长期目标是改善SSC在方法学上的可靠临床试验，并提高对SSC药物开发的兴趣。这项应用旨在开发SSC-CRI，作为弥漫性SSC临床试验的结果衡量标准。我们的中心假设是，弥漫性SSC患者的核心变量集可以用来开发具有稳健测试特征的SSC-CRI公式。我们对这项为期3年的计划的具体目标是：具体目标1.在200名弥漫性SSC患者中进行前瞻性纵向观察临床研究，以最近完成的Delphi练习为基础，为SSC-CRI确定一套可靠、有效和反应灵敏的SSC措施。具体目标2.采用前瞻性的、数据驱动的、建立共识的技术，制定和定量评估弥漫性SSC的SSC-CRI的候选定义。本申请中提出的研究具有重要意义，因为它有望为弥漫性SSC提供单一的SSC-CRI，从而为药物开发和改善临床试验中治疗药物的疗效评估提供动力。通俗语言：我们建议为弥漫性硬皮病的临床试验制定一个反应标准，以促进药物开发，并有望导致硬皮病的有效治疗。

DESCRIPTION (provided by applicant): Systemic sclerosis Scleroderma, (SSc) can be associated with a high morbidity and mortality. The complexity and heterogeneity of the disease mandates a composite response index that will capture different organ involvement and patient-reported outcomes. There is a critical need for an SSc-combined response index (SSc-CRI) to facilitate drug development and to allow comparison among clinical trials in SSc, as a similar index did in rheumatoid arthritis. We have assembled a group of international experts who have expertise in clinical trial design and development of response criteria in different arthritides. UCLA Clinical Coordinating Center has successfully coordinated recently concluded NIH-funded SSc clinical trials. We took the first step in the developing an SSc-CRI by conducting a structured Delphi exercise to develop a provisional core set of items for clinical trials. The Delphi exercise identified 11 domains relevant to diffuse SSc clinical trials. Our long-term goals are to improve methodologically sound SSc clinical trials and increase interest in drug development for SSc. This application aims to develop an SSc-CRI to be used as an outcome measure in diffuse SSc clinical trials. Our central hypothesis is that a core set of variables for patients with diffuse SSc can be used to develop a formula for an SSc-CRI with robust test characteristics. Our Specific Aims for the 3-year proposal are: Specific Aim 1. Perform a prospective longitudinal observational clinical study in 200 patients with diffuse SSc to define a reliable, valid and responsive set of SSc measures for an SSc-CRI, based on a recently completed Delphi exercise. Specific Aim 2. Employ a prospective, data-driven, consensus building techniques to develop and quantitatively evaluate candidate definitions for an SSc-CRI for diffuse SSc. The research proposed in this application is significant because it is expected to provide a single SSc-CRI for diffuse SSc, thereby providing an impetus for drug development and improved assessment of efficacy of therapeutic agents in clinical trials. Lay Language: We propose to develop a response criteria for clinical trials in diffuse scleroderma that can facilitate drug development and hopefully, can lead to effective treatments for scleroderma.