Experience using centralized spirometry in the phase 2 randomized, placebo-controlled, double-blind trial of denufosol in patients with mild to moderate cystic fibrosis

Abstract

Background Centralized spirometry may significantly improve quality of spirometry and reduce variability of this outcome measure in clinical trials in cystic fibrosis (CF). Methods Spirometry was performed during the phase 2 randomized, placebo-controlled, double-blind clinical trial of denufosol in patients with mild to moderate CF using American Thoracic Society guidelines. Uniform spirometers were used with electronic data transmission of all the data to a reading center. Spirometry was evaluated for quality by a central reader based on start of test, cough during the test, and evidence of a plateau. Results A total of 1418 spirometry values were assessed in 89 subjects during the trial. In only 5 instances did the central reading center need to give feedback to sites regarding the quality of spirometry. The study site data matched the central reading center's data for all but 78 (6%) spirometry values in 33 patients. Many of these differences were small with only 35 (3%) values differing by more than 50 mL in 26 patients. Conclusion Spirometry in this clinical trial was of high quality with low rate of significant centralized over-read.