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

尽管特发性肺疾病是肺间质性疾病（ILD）中最常见和最致命的疾病

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.