Direct likelihood analysis versus simple forms of imputation for missing data in randomized clinical trials.
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.
Beunckens
Caroline
C
Center for Statistics, Limburgs Universitair Centrum, Diepenbeek, Belgium.
Molenberghs
Geert
G
Kenward
Michael G
MG
D003625:Data Collection; D003627:Data Interpretation, Statistical; D006801:Humans; D016013:Likelihood Functions; D010352:Patient Dropouts; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D013223:Statistics as Topic / Q000379:methods*