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Published in: Trials 1/2016

Open Access 01-12-2016 | Research

Modelling variable dropout in randomised controlled trials with longitudinal outcomes: application to the MAGNETIC study

Authors: Ruwanthi Kolamunnage-Dona, Colin Powell, Paula Ruth Williamson

Published in: Trials | Issue 1/2016

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Abstract

Background

Clinical trials with longitudinally measured outcomes are often plagued by missing data due to patients withdrawing or dropping out from the trial before completing the measurement schedule. The reasons for dropout are sometimes clearly known and recorded during the trial, but in many instances these reasons are unknown or unclear. Often such reasons for dropout are non-ignorable. However, the standard methods for analysing longitudinal outcome data assume that missingness is non-informative and ignore the reasons for dropout, which could result in a biased comparison between the treatment groups.

Methods

In this article, as a post hoc analysis, we explore the impact of informative dropout due to competing reasons on the evaluation of treatment effect in the MAGNETIC trial, the largest randomised placebo-controlled study to date comparing the addition of nebulised magnesium sulphate to standard treatment in acute severe asthma in children. We jointly model longitudinal outcome and informative dropout process to incorporate the information regarding the reasons for dropout by treatment group.

Results

The effect of nebulised magnesium sulphate compared with standard treatment is evaluated more accurately using a joint longitudinal-competing risk model by taking account of such complexities. The corresponding estimates indicate that the rate of dropout due to good prognosis is about twice as high in the magnesium group compared with standard treatment.

Conclusions

We emphasise the importance of identifying reasons for dropout and undertaking an appropriate statistical analysis accounting for such dropout. The joint modelling approach accounting for competing reasons for dropout is proposed as a general approach for evaluating the sensitivity of conclusions to assumptions regarding missing data in clinical trials with longitudinal outcomes.

Trial registration

EudraCT number 2007-006227-12. Registration date 18 Mar 2008.
Appendix
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Metadata
Title
Modelling variable dropout in randomised controlled trials with longitudinal outcomes: application to the MAGNETIC study
Authors
Ruwanthi Kolamunnage-Dona
Colin Powell
Paula Ruth Williamson
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1342-0

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