Defining the natural history of sarcoidosis in a retrospective cohort to inform design of clinical trials

在回顾性队列中定义结节病的自然史，为临床试验的设计提供信息

• 批准号: 9372535
• 负责人: Alicia Gerke
• 金额: $ 15万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9372535
• 关键词: Defining; natural; history; sarcoidosis; retrospective

Project Summary/Abstract (Project Description). Sarcoidosis is a rare multi-system inflammatory disease that affects less than 185,000 patients in the United States per year with significant morbidity. It is an orphan disease with an unclear natural history and no known curative treatment. While a number of drugs are used clinically, none have proven efficacy in randomized clinical trials. This lack of progress in intervention trials is likely because 1) there is a flaw in subject selection since half of patients will resolve naturally, and 2) currently used primary outcome measures may not be the best indicator of drug efficacy. In order to select individual patients that would benefit from enrollment into clinical trials, determine the timing and type of outcomes that would reflect meaningful change, and to establish sample sizes that adequately show effect with the least amount of patients, it is critical to first understand the natural history of sarcoidosis. Our objective is to establish a large, inclusive, retrospective cohort of sarcoidosis patients and define the natural history of sarcoidosis in this population, including a comprehensive study of healthcare utilization and a longitudinal analysis of clinical outcomes. The central hypothesis is patients with sarcoidosis can be segregated into three cohorts (worsening, chronic, or improving) that reflect disease course at different times in the natural history of sarcoidosis. In order to design the most efficient clinical trials with the ability to show an effect size, the key is to predict which patients will have a worsening course, earlier in the natural history, to show the largest effect of an intervention. The rationale for this study is that, by defining the natural history of sarcoidosis, we can better predict at diagnosis the subset of patients who will clinically worsen and be the most appropriate candidates for intervention trials. The aims are the following: Aim 1. Build and validate a retrospective cohort of patients with sarcoidosis in a large population-based dataset. Using a multi-center retrospective dataset, our objective is to establish a cohort of at least 1500 sarcoidosis patients with linked claims and clinical data. A secondary goal is to better define the case definition of sarcoidosis with degrees of confidence based on claims codes, imaging results, and biopsy data. Aim 2. Establish the natural history of sarcoidosis based on health care utilization and clinical data prior to diagnosis of disease and thereafter. The objective is to define characteristics that distinguish between patients who are at differing points in the natural history and to define factors earlier the natural history of sarcoidosis that predict for disease worsening. Aim 3. Based on the change in outcomes of patients with worsening severity, calculate the sample size necessary to determine an effect on outcomes in clinical trials. By assessing change over time for various outcome measures, we will determine effect size, time course, and sample size for each outcome. Our long term objective of this study is that by defining the natural history of sarcoidosis randomized controlled studies can be more effectively designed for treatments.

项目概要/摘要（项目描述）。 结节病是一种罕见的多系统炎性疾病，在美国影响不到185，000例患者。 发病率高的州。它是一种罕见的疾病，自然史不清楚， 治愈性治疗虽然有许多药物在临床上使用，但没有一种药物在随机对照试验中证明有效。 临床试验干预试验缺乏进展可能是因为：1）受试者选择存在缺陷 由于一半的患者会自然消退，2）目前使用的主要结局指标可能不是 药物疗效的最佳指标。为了选择将从入组中获益的个体患者， 临床试验，确定反映有意义变化的结局的时间和类型，并建立 样本量，充分显示效果与最少量的患者，这是至关重要的，首先要了解 结节病的自然史我们的目的是建立一个大型的、包容性的、回顾性的结节病队列研究 患者，并确定结节病在这一人群中的自然史，包括一项全面的研究， 医疗保健利用和临床结果的纵向分析。中心假设是患者 结节病可分为三个队列（恶化、慢性或改善），反映疾病进程 在结节病自然史的不同时期。为了设计最有效的临床试验， 显示效应量的能力，关键是预测哪些患者将在治疗的早期出现恶化的病程。 自然史，以显示干预的最大效果。这项研究的基本原理是，通过定义 结节病的自然史，我们可以更好地预测在诊断的患者的子集， 恶化并成为干预试验的最合适候选人。目标如下：目标1。 在基于大人群的结节病患者中建立并验证回顾性队列 数据集。使用多中心回顾性数据集，我们的目标是建立一个至少1500人的队列 结节病患者的相关索赔和临床数据。第二个目标是更好地定义案例定义 根据索赔代码、成像结果和活检数据，以置信度评估结节病的诊断。目标二。 根据之前的医疗保健利用和临床数据建立结节病的自然史， 疾病的诊断和治疗。目标是定义区分以下各项的特征： 处于自然史不同阶段的患者，并在自然史早期确定因素， 预示着疾病恶化的结节病。目标3。根据患者结局的变化， 严重程度恶化，计算确定对临床结局的影响所需的样本量 审判通过评估各种结局指标随时间的变化，我们将确定效应大小、时间 每个结果的样本量。我们这项研究的长期目标是，通过定义自然 结节病史的随机对照研究可以更有效地设计治疗。