Provisional Combined Response Index For Patients With Diffuse Systemic Sclerosis

系统性硬化症(Score derma，SSC)具有较高的发病率和死亡率。这个 疾病的复杂性和异质性要求一个综合反应指数，该指数将反映不同的 器官受累和患者报告的结果。迫切需要一种SSC综合应对措施 索引(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，作为 类风湿性关节炎也有类似的症状。我们已经召集了一个国际专家小组，他们已经 擅长不同关节炎的临床试验设计和反应标准的制定。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。我们拿到了 开发SSC-CRI的第一步是进行结构化的Delphi练习，以开发 临床试验的临时核心项目集。Delphi练习确定了11个与漫反射相关的领域 SSC临床试验。我们的长期目标是改进在方法上合理的SSC临床试验，并增加 SSC对药物开发的兴趣。本应用程序旨在开发一个SSC-CRI，用作 弥漫性SSc临床试验中的结果衡量。我们的中心假设是一组核心变量 弥漫性SSC患者可以用来开发一种具有稳健测试特征的SSC-CRI公式。 我们对这项为期3年的建议的具体目标是： 特定目标1.对200例弥漫性SSc患者进行前瞻性纵向观察临床研究 根据最近的一项调查，为SSC-CRI定义一套可靠、有效和反应迅速的SSC措施 完成了Delphi练习。 具体目标2.使用前瞻性的、数据驱动的、建立共识的技术来开发和 定量评估漫反射SSC的SSC-CRI的候选定义。 本申请中提出的研究具有重要意义，因为它有望提供单一的SSC-CRI 为弥漫性SSC提供动力，从而促进药物开发和改进对 临床试验中的治疗剂。 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，该标准可以 促进药物开发，并有望导致硬皮病的有效治疗。

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 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 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 Aim1. 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.