Prospective tReatment EffiCacy in IPF uSlng genOtype for Nac Selection (PRECISIONS) trial and Molecular Endophenotyping in Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases study

尽管是最常见和最致命的间质性肺疾病(ILD)，特发性肺 纤维化(IPF)的诊断和治疗仍然具有挑战性。IPF的诊断过程依赖于主观性 临床数据的解释，而目前的抗肝纤维化治疗采用“一刀切”的范例。我们的 临床合作者一直站在开发组学方法的前沿，以诊断和确定 ILDS的预后。重要的是，他们确定了第一个药物基因组相互作用，表明IPF 携带rs3750920 TOLLIP T/T基因型的患者明显受益于N-乙酰半胱氨酸(NAC)的使用。我们的 该项目利用与肺纤维化基金会(PFF)患者登记和 生物库研究。这一组招募了具有广泛基线表型的ILD患者 和纵向结果数据、生物样本，并同意重新联系以供未来研究。 我们的总体目标是：1)使用PFF有效地进行一项基于新的精确的基于基因型的IPF试验 临床护理网络站点；以及2)广泛的ILDS的分子特征和识别遗传变异 与IPF风险相关。经验丰富的数据协调中心(DCC)，具有强大的统计领导力和 专业知识在设计和分析中都是关键，特别是在进行过程中出现意外问题时 一项临床试验。密歇根大学生物医学和教育研究的统计分析 (SABER)一流生物统计系的单位将担任DCC，汇集了一位经验丰富的 生物统计学、研究设计、项目管理、研究监测、数据库方面的教职员工小组 设计和数据管理，以及研究管理。Saber在合作方面有着良好的记录 与临床协调中心(CCC)和临床现场的参与肺部研究人员。这个 UM DCC的总体目标是与研究调查人员、CCC和NHLBI合作，以实现 按时并在预算范围内成功完成研究。我们将通过以下方式实现这些目标 三个具体目标：(1)通过提供统计和临床试验方法，提高科学严谨性 设计、分析和传播研究成果的专门知识；(2)确保及时、准确地收集 和可复制的数据，并最大限度地遵守研究方案；和(3)提供既定的 用于研究管理和运营以及研究之间通信的基础设施和服务 利益相关者。我们的领导力、经验和专业知识将促进合作，鼓励科学 生产力，并促进及时传播关于“精准医学时代”IPF诊断的结果，以及 由基因决定的临床试验的“精确”方法的好处。

Despite being the most frequent and deadly of the interstitial lung diseases (ILD), Idiopathic Pulmonary Fibrosis (IPF) remains challenging to diagnose and treat. The diagnostic process for IPF relies on subjective interpretations of clinical data while current antifibrotic therapies employ a “one size fits all” paradigm. Our clinical collaborators have been at the forefront of developing `omics approaches to diagnose and define prognosis in ILDs. Importantly, they identified the first pharmacogenomic interaction suggesting that IPF patients with rs3750920 TOLLIP T/T genotype strongly benefited from use of N-Acetylcysteine (NAC). Our project leverages existing partnerships with the Pulmonary Fibrosis Foundation (PFF) Patient Registry and Biorepository studies. This group has recruited ILD patients who have provided extensive baseline phenotypic and longitudinal outcome data, biological samples and have consented to be re-contacted for future research. Our overall objectives are to 1) efficiently conduct a novel precision genotype-based IPF trial using PFF Clinical Care Network sites; and 2) molecularly characterize a broad range of ILDs and identify genetic variants associated with IPF risk. An experienced Data Coordinating Center (DCC) with strong statistical leadership and expertise is key in both design and analysis, particularly when unanticipated issues arise during the conduct of a clinical trial. The University of Michigan Statistical Analysis of Biomedical and Educational Research (SABER) unit in a top-ranked Department of Biostatistics will serve as DCC, bringing together an experienced group of faculty and staff in biostatistics, research design, project management, study monitoring, database design and data management, and research administration. SABER has a strong track record of collaborations with the participating pulmonary investigators in the Clinical Coordinating Center (CCC) and clinical sites. The overarching goal of the UM DCC is to collaborate with study investigators, the CCC, and NHLBI to enable successful achievement of the study on time and within budget. We will accomplish these goals through the three specific aims: (1) Enhance scientific rigor by providing statistical and clinical trials methodological expertise to design, analyze and disseminate research findings; (2) Ensure the collection of timely, accurate and reproducible data, and maximize adherence to the study protocol; and (3) Provide established infrastructure and services for study administration and operations and for communication among study stakeholders. Our leadership, experience, and expertise will promote collaborations, encourage scientific productivity, and facilitate timely dissemination of findings on “precision medicine era” IPF diagnosis, and benefits of a “precision” approach with a genotype-driven clinical trial.