Methods for Handling Dropouts in Longitudinal Clinical Trials

Abstract
This paper focuses on the monotone missing data patterns produced by dropouts and presents a review of the statistical literature on approaches for handling dropouts in longitudinal clinical trials. A variety of ad hoc procedures for handling dropouts are widely used. The rationale for many of these procedures is not well‐founded and they can result in biased estimates of treatment comparisons. A fundamentally difficult problem arises when the probability of dropout is thought to be related to the specific value that in principle should have been obtained; this is often referred to asinformativeornon‐ignorabledropout. Joint models for the longitudinal outcomes and the dropout times have been proposed in order to make corrections for non‐ignorable dropouts. Two broad classes of joint models are reviewed:selectionmodels andpattern‐mixturemodels. Finally, when there are dropouts in a longitudinal clinical trial the goals of the analysis need to be clearly specified. In this paper we review the main distinctions between a ‘‘pragmatic’’ and an ‘‘explanatory’’ analysis. We note that many of the procedures for handling dropouts that are widely used in practice come closest to producing an explanatory rather than a pragmatic analysis.

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