Optimization of Outcome Measures For Clinical Trials in Children with Lupus

描述（由申请人提供）：尽管已经确定了几个有希望的药物靶点，并且对该疾病的病理学有了极大的了解，但还没有药物被批准用于治疗儿童期发作的SLE （cSLE）。批准的cSLE治疗方法严重缺乏的原因包括缺乏经过良好验证的，高性能的结果和反应措施，用于临床试验，以准确地从医生和患者的角度获取相关的治疗益处。本应用程序的目的是验证和校准由治疗医师和cSLE患者评定的cSLE临床相关变化的测量。待检验的主要假设是，改善的反应和结局指标有助于准确描述cSLE的临床相关治疗效果。在我们的研究方法中，除了前瞻性地收集100例cSLE患者的纵向数据外，我们还将利用来自南美、美国和英国的表型良好的cSLE队列（n= 1,800）的现有纵向数据。我们将通过追求以下具体目标来测试主要假设并实现本申请的目标：1：全面验证cSLE耀斑的初步标准，使用前瞻性cSLE注册，目标是实现ACR/ EULAR认可。目的2：提供增强的工具来捕获临床相关的cSLE治疗反应。目的3：开发一种改进的csl相关损伤量化评分算法。目的4：验证PROMIS（患者报告的结果测量信息系统）儿科简短表格在cSLE中的应用，重点关注临床相关的变化。在这项研究完成后，增强的结果测量将可用于cSLE临床试验的终点。这些旨在简化对患有cSLE的儿童和青少年的新型药物进行充分有力且成本较低的临床试验。此外，我们将从患者的角度描述cSLE的临床相关变化，利用NIH promise物项库提供的优越的缩放特性。

DESCRIPTION (provided by applicant): Despite the identification of several promising drug targets and a vastly expanded understanding in the pathoetiology of the disease, no drug has ever been approved for the treatment of childhood-onset SLE (cSLE). Reasons for this profound dearth of approved treatments for cSLE include the lack of well validated, high-performing outcome and response measures for use in clinical trials to accurately capture relevant treatment benefits, both from a physician and a patient perspective. The objective of this application is to validate and calibrate measures of clinically relevant changes in cSLE as rated by the treating physician and patients with cSLE. The principal hypothesis to be tested is that improved response and outcome measures facilitate the accurate delineation of clinically relevant treatment effects in cSLE. In our approach to this study, we will take advantage of available longitudinal data from well-phenotyped cSLE cohorts from South America, the United States of America, and the United Kingdom (n= >1,800), besides prospectively collecting longitudinal data on 100 cSLE patients. We will test the principal hypothesis and achieve the objective of this application by pursuing the following specific aims: 1: To comprehensively validate the Preliminary Criteria of cSLE Flare, using prospective cSLE registries with the goal of achieving ACR/ EULAR endorsement. Aim 2: To provide enhanced tools for capturing clinically relevant Response to Therapy with cSLE. Aim 3: To develop an improved scoring algorithm for quantifying cSLE-associated Damage. Aim 4: To validate the PROMIS (Patient-Reported Outcomes Measurement Information System) Pediatric Short Forms in cSLE, focusing on clinically relevant changes over time. Upon completion of this research, enhanced outcome measures will be available that are ready for use as endpoints in clinical trials of cSLE. These are destined to simplify the conduct of adequately powered & less costly clinical trials of novel medications for children and adolescents with cSLE. Furthermore, we will delineate clinically relevant changes in cSLE from a patient perspective, capitalizing on the superior scaling properties offered by the NIH PROMIS Item Banks.