Direct likelihood analysis versus simple forms of imputation for missing data in randomized clinical trials.
Beunckens, Caroline;
Molenberghs, Geert;
Kenward, Michael G;
(2005)
Direct likelihood analysis versus simple forms of imputation for missing data in randomized clinical trials.
Clinical trials (London, England), 2 (5).
pp. 379-386.
ISSN 1740-7745
DOI: https://doi.org/10.1191/1740774505cn119oa
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BACKGROUND: In many clinical trials, data are collected longitudinally over time. In such studies, missingness, in particular dropout, is an often encountered phenomenon. METHODS: We discuss commonly used but often problematic methods such as complete case analysis and last observation carried forward and contrast them with broadly valid and easy to implement direct-likelihood methods. We comment on alternatives such as multiple imputation and the expectation-maximization algorithm. RESULTS: We apply these methods in particular to data from a study with continuous outcomes. The outcomes are modelled using a general linear mixed-effects model. The bias with CC and LOCF is established in the case study and the advantages of the direct-likelihood approach shown. CONCLUSIONS: We have established formal but easy to understand arguments for a shift towards a direct-likelihood paradigm when analysing incomplete data from longitudinal clinical trials, necessitating neither imputation nor deletion.