title: Single time point comparisons in longitudinal randomized controlled trials: power and bias in the presence of missing data.
abstract: BACKGROUND
  The primary analysis in a longitudinal randomized controlled trial is sometimes a comparison of arms at a single time point. While a two-sample t-test is often used, missing data are common in longitudinal studies and decreases power by reducing sample size. Mixed models for repeated measures (MMRM) can test treatment effects at specific time points, have been shown to give unbiased estimates in certain missing data contexts, and may be more powerful than a two sample t-test.
  
  
  METHODS
  We conducted a simulation study to compare the performance of a complete-case t-test to a MMRM in terms of power and bias under different missing data mechanisms. Impact of within- and between-person variance, dropout mechanism, and variance-covariance structure were all considered.
  
  
  RESULTS
  While both complete-case t-test and MMRM provided unbiased estimation of treatment differences when data were missing completely at random, MMRM yielded an absolute power gain of up to 12 %. The MMRM provided up to 25 % absolute increased power over the t-test when data were missing at random, as well as unbiased estimation.
  
  
  CONCLUSIONS
  Investigators interested in single time point comparisons should use a MMRM with a contrast to gain power and unbiased estimation of treatment effects instead of a complete-case two sample t-test.
authors.affiliation: Department of Epidemiology and Biostatistics, University of Arizona, PO Box 245163, Tucson, AZ, 85724, USA. eashbeck@email.arizona.edu.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Ashbeck
authors.affiliation: Department of Epidemiology and Biostatistics, University of Arizona, PO Box 245163, Tucson, AZ, 85724, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Bell
mesh_terms: D015982:Bias; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
keywords: Complete-case; Longitudinal; Mean response profile; Missing data; Mixed model; Power; Repeated measures; T-test