title: Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint.
abstract: BACKGROUND
  Reduction in pulmonary exacerbations is an important efficacy endpoint for CF clinical studies. Powering exacerbation endpoints requires estimation of the future exacerbation incidence in CF study populations, but rates differ across the population.
  
  
  METHODS
  We have estimated exacerbation rates for Epidemiologic Study of CF subpopulations stratified by age, FEV(1)% predicted, sex, weight-for-age percentile, respiratory signs and symptoms, and history of exacerbation and bacterial culture. Sample sizes required to attain 80% power to detect exacerbation reductions of 20% to 80% in 1:1 randomized studies of 3 to 12 month duration were determined. Exacerbation treatments with "any" antibiotic (new oral quinolone, new inhaled antibiotic, or intravenous (IV) antibiotic) and with IV antibiotics were studied.
  
  
  RESULTS
  At all ages, decreased FEV(1), female sex, exacerbation history, and Pseudomonas aeruginosa culture history were associated with increased treatment for exacerbation.
  
  
  CONCLUSIONS
  These data should assist investigators in the design of future CF exacerbation studies.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, USA. enigmaster@comcast.net
authors.forename: D R
authors.initials: DR
authors.lastname: Vandevanter
authors.forename: A
authors.initials: A
authors.lastname: Yegin
authors.forename: W J
authors.initials: WJ
authors.lastname: Morgan
authors.forename: S J
authors.initials: SJ
authors.lastname: Millar
authors.forename: D J
authors.initials: DJ
authors.lastname: Pasta
authors.forename: M W
authors.initials: MW
authors.lastname: Konstan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003550:Cystic Fibrosis / Q000503:physiopathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D012107:Research Design / Q000706:statistics & numerical data*; D018401:Sample Size; D016896:Treatment Outcome; D055815:Young Adult