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）：尽管确定了几个有希望的药物靶标，并且对疾病的病理学有很大扩展的理解，但曾经没有批准药物来治疗儿童发作的SLE（CSLE）。批准的CSLE治疗方法的严重缺乏的原因包括缺乏经过良好验证的，高性能的结果和用于在临床试验中使用的响应措施，从医生和患者的角度准确地捕获相关的治疗益处。该应用的目的是验证和校准由治疗医师和CSLE患者评估的CSLE临床相关变化的度量。要测试的主要假设是改进的反应和结果度量促进了CSLE中临床相关治疗效应的准确描述。 在我们的这项研究方法中，我们将利用来自南美，美利坚合众国和英国的良好型CSLE队列中的可用纵向数据（n => 1,800）（n => 1,800），除了对100名CSLE患者收集纵向数据。 我们将通过追求以下特定目的来检验主假设，并实现本应用的目标：1：全面验证CSLE Flare的初步标准，使用前瞻性CSLE注册表，目的是实现ACR/ Eular认可。目标2：提供增强的工具来捕获CSLE对治疗的临床相关反应。 AIM 3：开发改进的评分算法，以量化与CSLE相关的损伤。 目标4：验证CSLE中的Promis（患者报告的结果测量信息系统）小儿短形式，重点是随着时间的推移临床相关的变化。这项研究完成后，将提供增强的结果指标，可以在CSLE的临床试验中用作终点。这些注定要简化用于CSLE儿童和青少年的新型药物的足够动力和成本较低的临床试验的行为。此外，我们将从患者的角度来描述CSLE的临床相关变化，并利用NIH Promis物品银行提供的出色缩放属性。