title: Performance of mixed effects models in the analysis of mediated longitudinal data.
abstract: BACKGROUND
  Linear mixed effects models (LMMs) are a common approach for analyzing longitudinal data in a variety of settings. Although LMMs may be applied to complex data structures, such as settings where mediators are present, it is unclear whether they perform well relative to methods for mediational analyses such as structural equation models (SEMs), which have obvious appeal in such settings. For some researchers, SEMs may be more difficult than LMMs to implement, e.g. due to lack of training in the methodology or the need for specialized SEM software. It therefore is of interest to evaluate whether the LMM performs sufficiently in a scenario particularly suitable for SEMs. We focus on evaluation of the total effect (i.e. direct and indirect) of an exposure on an outcome of interest when a mediating factor is present. Our aim is to explore whether the LMM performs as well as the SEM in a setting that is conducive to using the SEM.
  
  
  METHODS
  We simulated mediated longitudinal data from an SEM where a binary, main independent variable has both direct and indirect effects on a continuous outcome. We conducted analyses with both the LMM and SEM to evaluate the performance of the LMM in a setting where the SEM is expected to be preferable. Models were evaluated with respect to bias, coverage probability and power. Sample size, effect size and error distribution of the simulated data were varied.
  
  
  RESULTS
  Both models performed well in a range of settings. Marginal increases in power estimates were observed for the SEM, although generally there were no major differences in performance. Power for both models was good with a sample of size of 250 and a small to medium effect size. Bias did not substantially increase for either model when data were generated from distributions that were both skewed and kurtotic.
  
  
  CONCLUSIONS
  In settings where the goal is to evaluate the overall effects, the LMM excluding mediating variables appears to have good performance with respect to power, bias and coverage probability relative to the SEM. The major benefit of SEMs is that it simultaneously and efficiently models both the direct and indirect effects of the mediation process.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 715 Albany Street Crosstown Center-3rd Floor Boston, MA 02118, USA. emily.blood@childrens.harvard.edu
authors.forename: Emily A
authors.initials: EA
authors.lastname: Blood
authors.forename: Howard
authors.initials: H
authors.lastname: Cabral
authors.forename: Timothy
authors.initials: T
authors.lastname: Heeren
authors.forename: Debbie M
authors.initials: DM
authors.lastname: Cheng
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D015982:Bias; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D015658:HIV Infections; D006801:Humans; D008137:Longitudinal Studies; D015233:Models, Statistical; D012984:Software