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Review
. 2017 May;16(3):318-326.
doi: 10.1016/j.jcf.2017.01.002. Epub 2017 Jan 20.

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

Rhonda Szczesniak  1 , Sonya L Heltshe  2 , Sanja Stanojevic  3 , Nicole Mayer-Hamblett  4
Affiliations
Review

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

Rhonda Szczesniak et al. J Cyst Fibros. 2017 May.

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 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.

Keywords: Disease progression; FEV(1) endpoints; Longitudinal; Lung function; Spirometry.

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Conflict of interest statement

Conflicts of Interest

Author RS received support for this work from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number K25 HL125954. Author SLH received support for this work from the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number P30 DK089507. NMH received support for this work from the NIH UL1TR000423.

Figures

FIGURE 1
FIGURE 1. Shapes of FEV1 progression assumed in CF epidemiologic studies
The top panel (A1–D1) shows age-related FEV1 (expressed as % of predicted on the y-axis) over age (in years on the x-axis). The bottom panel (A2–D2) contains the corresponding rates of change, or derivatives, for the FEV1 curves from the top panel (expressed as annual rate of change in FEV1% predicted). Each black line or curve represents the age-related FEV1 trend that has been proposed in epidemiologic studies of long-term CF disease progression, including: linear progression (A1) that corresponds to a constant rate of decline (A2); piecewise or stratified models by age (B1) that correspond to constant rate of decline within each stratum (B2); curvelinear progression modeled with a quadratic term (C1), yielding rate of decline that becomes less severe with age (C2); a semiparametric model for more curvature at specific intervals of age (D1), producing rate of decline that can vary with age in a nonlinear manner (D2). Additional description is provided in Section 2.2.
See this image and copyright information in PMC

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