title: Use of FEV1in cystic fibrosis epidemiologic studies and clinical trials: A statistical perspective for the clinical researcher.
abstract: BACKGROUND
  Forced expiratory volume in 1s (FEV1) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV1surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV1.
  
  
  RESULTS
  In this review, we summarize from a statistical perspective the clinical relevance of FEV1based on its association with morbidity and mortality in CF, its role in epidemiologic studies of disease progression and comparative effectiveness, and its utility in clinical trials. In addition, we identify opportunities to advance epidemiologic research and the clinical development pipeline through further statistical considerations.
  
  
  CONCLUSIONS
  Our understanding of CF disease course, therapeutics, and clinical care has evolved immensely in the past decades, in large part due to the thoughtful application of rigorous research methods and meaningful clinical endpoints such as FEV1. A continued commitment to conduct research that minimizes the potential for bias, maximizes the limited patient population, and harmonizes approaches to FEV1analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care.
authors.affiliation: Division of Biostatistics & Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: Rhonda.Szczesniak@cchmc.org.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Szczesniak
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA, USA; Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stanojevic
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA, USA; Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
mesh_terms: D057186:Comparative Effectiveness Research / Q000379:methods; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000453:epidemiology; D018450:Disease Progression; D016021:Epidemiologic Studies; D005541:Forced Expiratory Volume; D006801:Humans
keywords: Disease progression; FEV(1) endpoints; Longitudinal; Lung function; Spirometry