Optimization of Outcome Measures For Clinical Trials in Children with Lupus

狼疮儿童临床试验结果指标的优化

• 批准号: 8924907
• 负责人: Hermine I Brunner
• 金额: $ 19.55万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8924907
• 关键词: Address; Adolescent; Adult; Advisory Committees; Algorithms; Am 80; American; Americas; Calibration; Caring; Child; Child health care; Childhood; Childhood Leukemia; Chronic Disease; Clinic; Clinical; Clinical Trials; Collaborations; Communities; Consensus; Data; Development; Disease; Drug Targeting; Enrollment; European; Flare; Funding; Future; Generic Drugs; Goals; Great Britain; Health; Information Systems; International; Label; Long-Term Effects; Lupus; Measurement; Measures; Medical; Medical Care Costs; Morbidity - disease rate; Onset of illness; Organ; Outcome; Outcome Measure; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Positioning Attribute; Professional Organizations; Property; Psychometrics; Public Health; Quality of life; Questionnaires; Registries; Research; Rheumatism; Rheumatology; Risk; Sample Size; Sensitivity and Specificity; South America; Statistical Methods; Surrogate Markers; Systemic Lupus Erythematosus; Testing; Therapeutic Effect; Time; United Kingdom; United States; United States National Institutes of Health; Validation; Weight; Work; base; clinically relevant; cohort; college; cost; disability; evidence base; experience; health related quality of life; improved; indexing; lupus registry; mortality; novel; outcome forecast; patient safety; prospective; response; tool; treatment effect; treatment response; young adult

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.

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 SLE（cSLE）。经批准的 cSLE 治疗方法严重缺乏的原因包括缺乏经过充分验证的、高性能的结果和反应措施，用于临床试验，以从医生和患者的角度准确捕捉相关的治疗益处。此应用程序的目的是验证和校准由治疗医生和 cSLE 患者评定的 cSLE 临床相关变化的测量值。要测试的主要假设是，改善的反应和结果测量有助于准确描述 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 个 cSLE 的纵向数据外，我们还将利用来自南美洲、美国和英国 (n= >1,800) 的表型良好的 cSLE 队列的可用纵向数据患者。 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：使用前瞻性 cSLE 注册中心全面验证 cSLE Flare 的初步标准，以实现 ACR/EULAR 认可。目标 2：提供增强工具来捕获 cSLE 治疗的临床相关反应。 目标 3：开发一种改进的评分算法来量化 cSLE 相关损伤。 目标 4：验证 cSLE 中的 PROMIS（患者报告结果测量信息系统）儿科简表，重点关注随时间推移的临床相关变化。这项研究完成后，将提供增强的结果测量，可用作 cSLE 临床试验的终点。这些旨在简化针对患有 cSLE 的儿童和青少年的新型药物的充分动力和成本较低的临床试验的进行。此外，我们将从患者的角度描绘 cSLE 的临床相关变化，利用 NIH PROMIS 项目库提供的卓越缩放特性。