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.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.
authors: Columbia University Medical Center, New York, NY.
authors: David J
authors: DJ
authors: Lederer
authors: InterMune, Inc, Brisbane, CA.
authors: Williamson Z
authors: WZ
authors: Bradford
authors: InterMune, Inc, Brisbane, CA.
authors: Elizabeth A
authors: EA
authors: Fagan
authors: Alfred Hospital, Melbourne, VIC, Australia.
authors: Ian
authors: I
authors: Glaspole
authors: University of Miami Miller School of Medicine, Miami, FL.
authors: Marilyn K
authors: MK
authors: Glassberg
authors: InterMune, Inc, Brisbane, CA.
authors: Kenneth F
authors: KF
authors: Glasscock
authors: InterMune, Inc, Brisbane, CA. Electronic address: davidlederer@columbia.edu.
authors: David
authors: D
authors: Kardatzke
authors: University of California, San Francisco, CA.
authors: Talmadge E
authors: TE
authors: King
authors: Vanderbilt University Medical Center, Nashville, TN.
authors: Lisa H
authors: LH
authors: Lancaster
authors: Inova Fairfax Hospital, Falls Church, VA.
authors: Steven D
authors: SD
authors: Nathan
authors: Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors: Carlos A
authors: CA
authors: Pereira
authors: Medical University of South Carolina, Charleston, SC.
authors: Steven A
authors: SA
authors: Sahn
authors: National Jewish Health, Denver, CO.
authors: Jeffrey J
authors: JJ
authors: Swigris
authors: Cedars-Sinai Medical Center, Los Angeles, CA.
authors: Paul W
authors: PW
authors: Noble
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011728:Pyridones / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone