Misspecification of at-risk periods and distributional assumptions in estimating COPD exacerbation rates: The resultant bias in treatment effect estimation.pdf (611.53 kB)
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Misspecification of at-risk periods and distributional assumptions in estimating COPD exacerbation rates: The resultant bias in treatment effect estimation.

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journal contribution
posted on 30.04.2018, 12:13 by Martin Law, Michael J. Sweeting, G. C. Donaldson, J. A. Wedzicha
In trials comparing the rate of chronic obstructive pulmonary disease exacerbation between treatment arms, the rate is typically calculated on the basis of the whole of each patient's follow-up period. However, the true time a patient is at risk should exclude periods in which an exacerbation episode is occurring, because a patient cannot be at risk of another exacerbation episode until recovered. We used data from two chronic obstructive pulmonary disease randomized controlled trials and compared treatment effect estimates and confidence intervals when using two different definitions of the at-risk period. Using a simulation study we examined the bias in the estimated treatment effect and the coverage of the confidence interval, using these two definitions of the at-risk period. We investigated how the sample size required for a given power changes on the basis of the definition of at-risk period used. Our results showed that treatment efficacy is underestimated when the at-risk period does not take account of exacerbation duration, and the power to detect a statistically significant result is slightly diminished. Correspondingly, using the correct at-risk period, some modest savings in required sample size can be achieved. Using the proposed at-risk period that excludes recovery times requires formal definitions of the beginning and end of an exacerbation episode, and we recommend these be always predefined in a trial protocol.

History

Citation

Pharmaceutical Statistics, 2017, 16 (3), pp. 201-209

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

Pharmaceutical Statistics

Publisher

Wiley

issn

1539-1604

eissn

1539-1612

Acceptance date

11/11/2016

Copyright date

2016

Available date

30/04/2018

Publisher version

https://onlinelibrary.wiley.com/doi/abs/10.1002/pst.1798

Language

en