@article{a5371ec268ab4a24a693d2611a0369ff,
title = "Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis",
abstract = "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",
author = "Lederer, {David J.} and Bradford, {Williamson Z.} and Fagan, {Elizabeth A.} and Ian Glaspole and Glassberg, {Marilyn K.} and Glasscock, {Kenneth F.} and David Kardatzke and King, {Talmadge E.} and Lancaster, {Lisa H.} and Nathan, {Steven D.} and Pereira, {Carlos A.} and Sahn, {Steven A.} and Swigris, {Jeffrey J.} and Noble, {Paul W.}",
note = "Funding Information: FUNDING/SUPPORT: This study was sponsored by InterMune (Brisbane, CA). Funding Information: Financial/nonfinancial disclosures: The authors have reported to the following conflicts of interest: Drs Lederer, Fagan, Glaspole, Glassberg, King, Lancaster, Nathan, Pereira, Sahn, Swigris, and Noble served as members of the ASCEND study steering committee. Dr Lederer has served on a scientific advisory board for Boehringer Ingelheim GmbH, Gilead, ImmuneWorks, and InterMune. Dr Glaspole has received honoraria from Boehringer Ingelheim GmbH. Dr King has served as a consultant for Actelion Pharmaceuticals Ltd, Boehringer Ingelheim GmbH, Daiichi Sankyo Company Limited, ImmuneWorks, and InterMune. Dr Lancaster has served on a scientific advisory board for Boehringer Ingelheim GmbH and InterMune and as a consultant to Boehringer Ingelheim GmbH. Dr Nathan has served on a scientific advisory board and received research funding from InterMune; he has also received research funding and served as a consultant for Boehringer Ingelheim GmbH, Gilead, and Genentech, Inc. Dr Pereira has received a research grant from InterMune. Dr Swigris has served on a scientific advisory board and received research funding from InterMune, and served as a consultant to Boehringer Ingelheim GmbH and Genentech, Inc. Dr Noble has served as a consultant for Boehringer Ingelheim GmbH; Bristol-Meyers Squibb Company; InterMune; Moerae Matrix; Genentech, Inc; and Takeda Pharmaceutical Company Limited. Drs Bradford, Fagan, and Kardatzke and Mr Glasscock are employees of InterMune. Publisher Copyright: {\textcopyright} 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS.",
year = "2015",
month = jul,
day = "1",
doi = "10.1378/chest.14-2817",
language = "English (US)",
volume = "148",
pages = "196--201",
journal = "Diseases of the chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "1",
}