Use of FEV₁ in cystic fibrosis epidemiologic studies and clinical trials: A statistical perspective for the clinical researcher

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 FEV₁ surveillance 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 FEV₁ based 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 FEV₁ analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care.