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Original Research: Diffuse Lung Disease |

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary FibrosisPirfenidone for Idiopathic Pulmonary Fibrosis

David J. Lederer, MD, FCCP; Williamson Z. Bradford, MD, PhD; Elizabeth A. Fagan, MD; Ian Glaspole, MBBS, PhD; Marilyn K. Glassberg, MD, FCCP; Kenneth F. Glasscock, BA; David Kardatzke, PhD; Talmadge E. King, Jr, MD, FCCP; Lisa H. Lancaster, MD, FCCP; Steven D. Nathan, MD, FCCP; Carlos A. Pereira, MD; Steven A. Sahn, MD; Jeffrey J. Swigris, DO; Paul W. Noble, MD
Author and Funding Information

From the Columbia University Medical Center (Dr Lederer), New York, NY; InterMune, Inc (Drs Bradford, Fagan, and Kardatzke and Mr Glasscock), Brisbane, CA; the Alfred Hospital (Dr Glaspole), Melbourne, VIC, Australia; the University of Miami Miller School of Medicine (Dr Glassberg), Miami, FL; the University of California, San Francisco (Dr King), San Francisco, CA; the Vanderbilt University Medical Center (Dr Lancaster), Nashville, TN; Inova Fairfax Hospital (Dr Nathan), Falls Church, VA; the Paulista School of Medicine (Dr Pereira), Federal University of São Paulo, São Paulo, Brazil; the Medical University of South Carolina (Dr Sahn), Charleston, SC; National Jewish Health (Dr Swigris), Denver, CO; and the Cedars-Sinai Medical Center (Dr Noble), Los Angeles, CA.

CORRESPONDENCE TO: David J. Lederer, MD, FCCP, Columbia University Medical Center, 622 W 168th St, PH14-101, New York, NY 10032; e-mail: davidlederer@columbia.edu


FUNDING/SUPPORT: This study was sponsored by InterMune (Brisbane, CA).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(1):196-201. doi:10.1378/chest.14-2817
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BACKGROUND:  FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF.

METHODS:  Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC.

RESULTS:  The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis.

CONCLUSIONS:  Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov


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