title: Analyzing incomplete longitudinal clinical trial data.
abstract: Using standard missing data taxonomy, due to Rubin and co-workers, and simple algebraic derivations, it is argued that some simple but commonly used methods to handle incomplete longitudinal clinical trial data, such as complete case analyses and methods based on last observation carried forward, require restrictive assumptions and stand on a weaker theoretical foundation than likelihood-based methods developed under the missing at random (MAR) framework. Given the availability of flexible software for analyzing longitudinal sequences of unequal length, implementation of likelihood-based MAR analyses is not limited by computational considerations. While such analyses are valid under the comparatively weak assumption of MAR, the possibility of data missing not at random (MNAR) is difficult to rule out. It is argued, however, that MNAR analyses are, themselves, surrounded with problems and therefore, rather than ignoring MNAR analyses altogether or blindly shifting to them, their optimal place is within sensitivity analysis. The concepts developed here are illustrated using data from three clinical trials, where it is shown that the analysis method may have an impact on the conclusions of the study.
authors.affiliation: Center for Statistics, Limburgs Universitair Centrum, Universitaire Campus, B-3590 Diepenbeek, Belgium. geert.molenberghs@luc.ac.be
authors.forename: Geert
authors.initials: G
authors.lastname: Molenberghs
authors.forename: Herbert
authors.initials: H
authors.lastname: Thijs
authors.forename: Ivy
authors.initials: I
authors.lastname: Jansen
authors.forename: Caroline
authors.initials: C
authors.lastname: Beunckens
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kenward
authors.forename: Craig
authors.initials: C
authors.lastname: Mallinckrodt
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Carroll
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003863:Depression / Q000188:drug therapy; D006801:Humans; D008137:Longitudinal Studies; D010352:Patient Dropouts
chemical_list: D000928:Antidepressive Agents