Mycobacterium avium complex Core Outcomes Research (MACCOR)

项目摘要/摘要 肺炎分枝杆菌复合体(MAC)是一种慢性感染和呼吸道炎症性疾病，具有 影响我们患者生活的多个方面的系统性表现。类似于其他慢性炎症 疾病，如类风湿性关节炎，对肺部MAC疾病(PMACd)的影响在 关于呈现、疗程和对治疗的反应的个人。终身管理往往是 必需的，因为反复出现是很常见的。患者通常服用3-5种抗生素，治疗负担很大。 18-24个月。在临床实践中，痰培养结果、X线表现和症状驱动 治疗决定。虽然痰培养转为阴性意味着微生物学上的成功，但它并不是 这意味着要根除感染，评估这种疾病对我们患者生活的全面影响是不够的。 重要的是，美国食品和药物管理局并不认为文化转变是一个适当的终点 在pMACd的治疗试验中。随着人们认识到这种疾病的发病率正在增加，而且它的 对抗生素的巨大需求尚未得到满足，一系列针对这种孤儿疾病的新疗法已经到位 最近出现了。然而，随机临床试验目前因缺乏有效的结果而受阻。 措施。客观测量功能、与健康相关的生活质量、放射学变化和生物标志物 都需要作为临床结果。此外，这种疾病自然历史的异质性反映在 事实上，培养、放射学和症状学通常不会同时改变。综合结果 根据几个领域(症状、放射学等)进行测量将更好地捕捉疾病活动，并可能是 在临床和新疗法的临床试验中都很有用。目前，还没有经过验证的结果 在所有研究中，pMACd和潜在结果的测量并不是一致的。为了 促进未来综合疾病活动措施的发展，这项建议旨在确定一套 核心成果领域和最小核心成果衡量的最佳可用工具集 可以在未来的临床试验中持续收集。首先，我们将确定一组核心结果域 对于对患者、护理人员、患者倡导者、临床专家和研究人员至关重要的pMACd，通过 使用德尔福方法的国际共识进程。第二，我们将评估 代表已识别岩心的各种可用测量仪器上的肺MAC治疗 结果领域，通过利用可用的临床数据集。第三，我们将确定最低核心成果 通过国际Delphi为未来的pMACd临床试验提供必要的测量仪器 协商一致的过程。这将使临床试验和荟萃分析之间的比较成为可能，两者在 一种罕见的疾病，如肺部MAC。该项目的成果将大大有助于 改善临床护理、未来的治疗试验和观察研究，除促进 PMACD疾病活动性综合测量的未来发展。

PROJECT SUMMARY/ABSTRACT Pulmonary Mycobacterium avium complex (MAC) is a chronic infection and airway inflammatory disease with systemic manifestations affecting multiple aspects of our patients' lives. Similar to other chronic inflammatory diseases, such as rheumatoid arthritis, the impact of pulmonary MAC disease (pMACd) varies between individuals with regards to presentation, course and response to therapy. Lifelong management is often required, as recurrence is common. The treatment burden is high with patients typically taking 3-5 antibiotics for 18-24 months. In clinical practice, sputum culture results, radiographic findings, and symptoms drive treatment decisions. While conversion of sputum culture to negative implies microbiologic success, it does not imply infection eradication and it is inadequate to assess the full impact of this disease on our patients' lives. Importantly, the US Food and Drug Administration does not consider culture conversion an adequate endpoint in therapeutic trials for pMACd. As this disease has become recognized to be increasing in incidence and its tremendous unmet need for antibiotics highlighted, a pipeline of new therapeutics for this orphan disease has recently materialized. However randomized clinical trials are currently stymied by a lack of validated outcome measures. Objective measures of function, health-related quality of life, radiographic changes and biomarkers are needed as clinical outcomes. Further, the heterogeneity of this disease's natural history is reflected by the fact that culture, radiography, and symptomatology often do not change together. A combined outcome measure along several domains (symptoms, radiologic, etc.) would better capture disease activity and could be useful both clinically as well as in clinical trials of new therapeutics. Currently, there are no validated outcome measures in pMACd and potential outcomes are not measured consistently across all studies. In order to facilitate development of a future combined disease activity measure, this proposal aims to identify a set of core outcome domains and the best available instruments for a minimum core outcome measurement set that can be consistently collected across future clinical trials. First, we will identify a set of core outcome domains for pMACd essential to patients, caregivers, patient advocates, clinical experts, and researchers through an international consensus process using the Delphi methodology. Second, we will evaluate the impact of pulmonary MAC treatment on various available measurement instruments that represent the identified core outcome domains, by utilizing available clinical datasets. Third, we will identify a minimum core outcome measurement instrument set essential for future pMACd clinical trials through the international Delphi consensus process. This will enable comparisons between clinical trials and meta-analyses, both important in a rare disease such as pulmonary MAC. The results of this project will contribute significantly to an improvement in clinical care, future therapeutic trials and observational research, in addition to facilitating future development of a combined disease activity measure in pMACd.