Optimization of Outcome Measures For Clinical Trials in Children with Lupus

描述（由申请人提供）：尽管已经确定了几种有希望的药物靶点，并且对疾病的病因学有了广泛的了解，但尚未有药物被批准用于治疗儿童期发作的SLE（cSLE）。cSLE获批治疗严重缺乏的原因包括缺乏经过充分验证的、高性能的结局和反应措施，用于临床试验，以从医生和患者的角度准确获取相关治疗获益。本申请的目的是验证和校准治疗医生和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应答和结局指标有助于准确描述cSLE的临床相关治疗效果。 在本研究的方法中，除了前瞻性收集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（n= > 1，800）的良好表型cSLE队列的可用纵向数据。 我们将通过追求以下具体目标来检验主要假设并实现本申请的目的：1：使用前瞻性cSLE登记研究全面验证cSLE突发的初步标准，目标是获得ACR/ EULAR认可。目的2：提供用于捕获cSLE临床相关治疗反应的增强工具。 目的3：开发一种用于量化cSLE相关损伤的改进评分算法。 目标4：验证PROMIS（患者报告结局测量信息系统）儿科简表在cSLE中的作用，重点关注随时间推移的临床相关变化。本研究完成后，将提供增强的结局指标，可用作cSLE临床试验的终点。这些都是注定要简化充分的权力和成本较低的临床试验的儿童和青少年与cSLE的新药物的行为。此外，我们将从患者的角度描述cSLE的临床相关变化，利用NIH PROMIS项目库提供的上级缩放特性。

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.