title: Predictors of Mortality Poorly Predict Common Measures of Disease Progression in Idiopathic Pulmonary Fibrosis.
abstract: Mortality prediction is well studied in idiopathic pulmonary fibrosis (IPF), but little is known about predictors of premortality disease progression. Identification of patients at risk for disease progression would be useful for clinical decision-making and designing clinical trials.
  
  
  
  To develop prediction models for disease progression in IPF.
  
  
  
  In a large clinical trial cohort of patients with IPF (n = 1,113), we comprehensively screened multivariate models of candidate baseline and past-change predictors for disease progression defined by 48-week worsening of FVC, dyspnea (University of California, San Diego Shortness of Breath Questionnaire [UCSD SOBQ]), 6-minute-walk distance (6MWD), and occurrence of respiratory hospitalization, or death. Progression outcomes were modeled as appropriate, by slope change using linear regression models and time to binary outcomes using Cox proportional hazards models.
  
  
  
  The overall cohort experienced considerable disease progression. Top-performing prediction models did not meaningfully predict most measures of disease progression. For example, prediction modeling explained less than or equal to 1% of the observed variation in 48-week slope change in FVC, UCSD SOBQ, and 6MWD. Models performed better for binary measures of time to disease progression but were still largely inaccurate (cross-validated C statistic ≤0.63 for ≥10% decline in FVC or death, ≤0.68 for ≥20-U increase in UCSD SOBQ or death, ≤0.70 for ≥100 m decline in 6MWD or death). Models for time to respiratory hospitalization or death (C statistic ≤0.77) or death alone (C statistic ≤0.81) demonstrated acceptable discriminative performance.
  
  
  
  Clinical prediction models poorly predicted physiologic and functional disease progression in IPF. This is in contrast to respiratory hospitalization and mortality prediction.
authors.affiliation: 1 Department of Medicine and.
authors.forename: Brett
authors.initials: B
authors.lastname: Ley
authors.affiliation: 2 InterMune Inc., Brisbane, California.
authors.forename: Williamson Z
authors.initials: WZ
authors.lastname: Bradford
authors.affiliation: 3 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.affiliation: 4 Policy Analysis Inc., Brookline, Massachusetts; and.
authors.forename: Derek
authors.initials: D
authors.lastname: Weycker
authors.affiliation: 5 Imperial College, London, United Kingdom.
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
authors.affiliation: 1 Department of Medicine and.
authors.forename: Harold R
authors.initials: HR
authors.lastname: Collard
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018450:Disease Progression; D004417:Dyspnea / Q000209:etiology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D015233:Models, Statistical; D016016:Proportional Hazards Models; D011728:Pyridones / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014797:Vital Capacity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone
keywords: 6-minute-walk distance; dyspnea; forced vital capacity; hospitalization; interstitial lung disease