Mycobacterium avium complex Core Outcomes Research (MACCOR)

鸟分枝杆菌复合体核心结果研究 (MACCOR)

• 批准号: 10683244
• 负责人: Cara Varley
• 金额: $ 17.01万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683244
• 关键词: Advocate; Affect; Antibiotics; Biological; Biological Markers; Caregivers; Clinical; Clinical Data; Clinical Research; Clinical Trials; Complex; Consensus; Data Set; Development; Disease; Family member; Funding; Future; Incidence; Individual; Infection; Inflammatory; International; Lung; Measurement; Measures; Meta-Analysis; Methodology; Mycobacterium avium Complex; Observational Study; Outcome; Outcome Assessment; Outcome Measure; Outcomes Research; Patient Education; Patient Outcomes Assessments; Patients; Process; Property; Radiology Specialty; Rare Diseases; Recurrence; Research; Research Personnel; Rheumatoid Arthritis; Sputum; Symptoms; Therapeutic Trials; United States Food and Drug Administration; chronic infection; chronic inflammatory disease; clinical care; clinical practice; disease heterogeneity; disease natural history; health related quality of life; improved; instrument; mycobacterial; novel therapeutics; radiological imaging; randomized, clinical trials; research study; success; symptomatology; treatment response

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.

项目摘要/摘要 肺鸟分枝杆菌复合体（MAC）是一种慢性感染和气道炎症性疾病， 影响患者生活多个方面的系统性表现。与其他慢性炎症相似 类风湿性关节炎等疾病时，肺MAC疾病（pMACd）的影响在 个人关于介绍，过程和对治疗的反应。终身管理往往是 这是必要的，因为复发是常见的。治疗负担很高，患者通常服用3-5种抗生素 18-24个月。在临床实践中，痰培养结果，放射学发现和症状驱动 治疗决定。虽然痰培养转为阴性意味着微生物学成功，但这并不意味着 这意味着根除感染，不足以评估这种疾病对我们患者生活的全面影响。 重要的是，美国食品和药物管理局并不认为培养转化是一个足够的终点 在pMACd的治疗试验中。由于这种疾病已被公认为是增加的发病率和其 对抗生素的巨大未满足的需求突显出来，针对这种孤儿疾病的新疗法的管道已经 最近实现了。然而，随机临床试验目前因缺乏有效的结果而受阻 措施功能、健康相关生活质量、影像学变化和生物标志物的客观指标 作为临床结果。此外，这种疾病的自然史的异质性反映在 事实上，文化，放射学和医学往往不会一起改变。综合结果 沿着几个领域（症状、放射学等）进行测量可以更好地捕捉疾病活动， 其在临床上以及在新疗法的临床试验中均有用。目前，没有经过验证的结果 在所有研究中，pMACd和潜在结局的测量结果并不一致。为了 为了促进未来综合疾病活动措施的发展，本建议旨在确定一套 核心成果领域和现有最佳工具，用于一套最低限度的核心成果计量， 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成果领域 对于患者、护理人员、患者倡导者、临床专家和研究人员至关重要的pMACd， 采用德尔菲方法进行国际协商。第二，我们将评估 在代表已确定核心的各种可用测量仪器上进行肺MAC治疗 结果域，通过利用现有的临床数据集。第三，我们将确定一个最低核心成果， 通过国际德尔菲测试，为pMACd临床试验提供必备的测量仪器 协商一致进程。这将使临床试验和荟萃分析之间的比较成为可能，这两个方面都很重要。 一种罕见的疾病，如肺MAC。该项目的成果将大大有助于 临床护理、未来治疗试验和观察性研究的改进， pMACd中联合疾病活动性测量的未来发展。