title: Study design implications of death and hospitalization as end points in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  The feasibility of an interventional clinical trial in idiopathic pulmonary fibrosis (IPF) using death and hospitalization as primary end points is an area of uncertainty. Using data from a large well-characterized clinical trial population, this article aims to illustrate the impact of cohort enrichment and study duration on sample size requirements for IPF clinical trials in which death alone or death plus hospitalization serve as the primary end point.
  
  
  METHODS
  Event rate estimates for death and hospitalization were determined from patients enrolled in National Institutes of Health-sponsored IPF Clinical Research Network clinical trials. Standard equations were applied to estimate the total sample size required for varying gender, age, and pulmonary function (GAP) stage-based cohorts.
  
  
  RESULTS
  Risk estimates for death and hospitalization in the clinical trial cohort were substantially lower than those published. An IPF trial with death as its primary end point enrolling subjects designated as GAP stage 1 and 2 over 1 year with a minimum follow-up of 1 year would require an estimated 7,986 subjects to achieve 90% power for a hazard ratio of 0.70. Alternatively, an IPF trial with death plus hospitalization as its primary end point enrolling subjects with GAP stage 2 and 3 over 2 years with a minimum follow-up of 1 year would require an estimated 794 subjects for the same power and hazard ratio.
  
  
  CONCLUSIONS
  Study design decisions, in particular cohort enrichment strategies, have a substantial impact on sample size requirements for IPF clinical trials using time-to-event primary end points such as death and death plus hospitalization.
authors.affiliation: From the Department of Medicine, University of California San Francisco, San Francisco, CA. Electronic address: hal.collard@ucsf.edu.
authors.forename: Harold R
authors.initials: HR
authors.lastname: Collard
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, MI.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Rhonda S
authors.initials: RS
authors.lastname: Roberts
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
mesh_terms: D000368:Aged; D002423:Cause of Death / Q000639:trends; D005240:Feasibility Studies; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000401:mortality* / Q000628:therapy*; D008297:Male; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology