Proceedings of the American Thoracic Society
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Review
Novel outcomes and end points: biomarkers in chronic obstructive pulmonary disease clinical trials.
Biomarker development in chronic obstructive pulmonary disease (COPD) is a nascent field, in part because of the complexity underlying COPD pathogenesis. The objective of this review is to provide examples of how biomarkers may be effectively applied in clinical trials of COPD by limiting their use to specific contexts and using them to answer well delineated questions. Types of novel outcomes or "biomarkers" that may be useful in clinical trials in COPD include analyses performed on bronchoscopically obtained samples, sputum, exhaled gases, blood, and urine and "ex vivo" assays performed using biological samples obtained from trial participants. ⋯ Examples given in this review include outcomes used in a phase IIA study of an inhaled small molecule inhibitor of epidermal growth factor receptor. Large observational studies of COPD, including the ECLIPSE, COPDGene, and SPIROMICS studies will further inform our use of biomarkers in COPD clinical trials. To encourage the application of novel biomarkers in clinical trials, the Food and Drug Administration has developed a new process for biomarker "qualification." This process has been designed to be more efficient and to promote consensus building and sharing of preclinical data.
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Chronic obstructive pulmonary disease (COPD) has been a major public health problem during the 20th century, and will remain a challenge for the foreseeable future. Worldwide, COPD is in the spotlight, because its high prevalence, morbidity, and mortality create formidable challenges for healthcare systems. However, there remain many ongoing, contentious issues in COPD, including the definition and staging of COPD itself. ⋯ Cigarette smoking is the principal causal factor, but other factors play a role in causing and triggering COPD. Likely, the clinical presentation of COPD and its contributing phenotypes within the remainder of the 21st century will be different than the "blue bloaters" and "pink puffers" observed one or two generations ago. Hopefully, the COPD clinical course will shift to better outcomes and prognosis than in the past.