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

项目摘要/摘要(项目描述)。 结节病是一种罕见的多系统炎症性疾病，在美国影响不到18.5万名患者。 这些国家每年的发病率都很高。它是一种孤儿疾病，自然病史不清楚，也没有已知的 根治疗法。虽然有许多药物在临床上使用，但没有一种药物在随机试验中证明有效 临床试验。干预试验缺乏进展可能是因为1)受试者的选择存在缺陷 由于一半的患者会自然缓解，以及2)目前使用的主要结果衡量标准可能不是 是药物疗效的最佳指标。为了选择将从登记中受益的个别患者 临床试验，确定反映有意义变化的结果的时间和类型，并建立 样本大小足以显示效果的患者数量最少，关键是首先要了解 结节病的自然病史。我们的目标是建立一个大型的、包容性的、回顾性的结节病队列。 患者和定义该人群中结节病的自然病史，包括对 医疗保健利用和临床结果的纵向分析。中心假设是患者患有 结节病可分为三组(恶化、慢性或改善)，以反映病程。 在结节病的自然历史上的不同时期。为了设计最有效的临床试验 显示效果大小的能力，关键是预测哪些患者的病程会在早期恶化 自然历史，展示一次干预的最大效果。这项研究的基本原理是，通过定义 结节病的自然病史，我们可以更好地预测诊断时临床上会 病情恶化，成为干预试验最合适的候选对象。目标如下：目标1。 建立和验证基于大规模人群的结节病患者的回顾性队列 数据集。使用多中心回顾数据集，我们的目标是建立至少1500人的队列 结节病患者有关联的索赔和临床资料。次要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，对结节病的可信度进行评估。目标2. 根据卫生保健利用情况和之前的临床数据建立结节病的自然病史 疾病的诊断和此后。目标是定义区分以下各项的特征 在自然病程中处于不同时间点的患者，并更早地确定自然病史的因素 预示疾病恶化的结节病。目的3.根据患者预后的变化 恶化的严重程度，计算确定对临床结果的影响所需的样本量 审判。通过评估各种结果指标随时间的变化，我们将确定效果大小、时间 当然，以及每个结果的样本量。我们这项研究的长期目标是通过定义自然的 结节病病史的随机对照研究可以更有效地设计用于治疗。

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.