Highlights
- •In randomized controlled trials that used the Lung Clearance Index as an outcome, there is a discordance between planned sample size required to observe statistically significant treatment effects and the magnitude of the treatment effects that are observed.
- •Large improvements in Lung Clearance Index for a few individuals can influence the interpretation of the effect size and may bias prospective sample size calculations.
- •Lung clearance index requires as little as 1/3 of the total sample size to detect equivalent changes with spirometry endpoints such as forced expiratory volume in 1 second (FEV1).
Abstract
Background
With the increasing availability of highly effective modulators for people living
with cystic fibrosis (CF), there is a need to re-design research studies to reflect
the changing epidemiology of the CF population. The lung clearance index (LCI), a
sensitive physiological measure of lung function, may be ideally suited as an endpoint
in the era of CF modulator therapies. In this study we describe study design considerations
for implementing LCI into interventional and observational research.
Methods
Simulations were used to estimate the required sample size to detect a range of treatment
effects for interventional studies (including cross-over trials) and to track lung
disease progression in observational studies.
Results
Using published treatment effects to inform the design of prospective studies can
lead to inefficient study designs. Large improvements in LCI for a few individuals
can skew results and can influence interpretations of treatment effects. Adjusting
for baseline LCI can help to improve the efficiency of a study. Compared to the forced
expiratory volume in 1 second (FEV1), analysis using LCI as an endpoint requires as little as one third of the total
sample size.
Conclusions
Planning of prospective studies that include LCI as an endpoint need to consider baseline
LCI and disease severity of the study population; whereas interpretation of results
needs to consider whether a few individuals skew the overall treatment effect.
Keywords
Abbreviations:
LCI (Lung Clearance Index)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: November 16, 2022
Accepted:
November 10,
2022
Received in revised form:
October 16,
2022
Received:
July 22,
2022
Publication stage
In Press Corrected ProofFootnotes
✰This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
