title: Analyses of efficacy end points in a controlled trial of interferon-gamma1b for idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a devastating disease, yet validated, reliable criteria for evaluating patient response to therapies in clinical trials are lacking.
  
  
  METHODS
  To optimize selection of end point criteria for the study of interferon (IFN)-gamma1b in patients with IPF, we retrospectively analyzed the components of the primary efficacy end point used in a large, controlled study of 330 patients for reliability, validity, and sensitivity to treatment effect. The primary end point components were death, disease progression defined as a > or = 5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O2), and disease progression defined as a > or = 10% decrease in percentage of predicted FVC.
  
  
  RESULTS
  We found that the P(A-a)O2 criterion was not reliable and was not associated with mortality. In contrast, the FVC criterion was reliable and was associated with a 2.4-fold increase in the risk of death. Of the three measures, only mortality was sensitive to a treatment effect of IFN-gamma1b. Additionally, the tendency for mortality benefit was observed in nearly all patient subgroups defined by baseline physiology. The effect of IFN-gamma1b on mortality was strongest in patients with baseline percentage of predicted FVC > or = 55% (p = 0.004) or percentage of predicted diffusing capacity of the lung for carbon monoxide > or = 30% (p = 0.008).
  
  
  CONCLUSIONS
  We conclude that mortality is the most inclusive end point for future trials of IFN- gamma1b in patients with IPF, and that a > 10% decrement in the percentage of predicted FVC represents a valid measure of disease progression.
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA 94110, USA. tking@medsfgh.ucsf.edu
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
authors.forename: Sharon
authors.initials: S
authors.lastname: Safrin
authors.forename: Karen M
authors.initials: KM
authors.lastname: Starko
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D012189:Retrospective Studies; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D011994:Recombinant Proteins; D007371:Interferon-gamma