Analysis of Data from a Controlled Repeated Measurements Design with Baseline-Dependent Dropouts

Abstract

Abstract. Differences in mean rates of change are of primary interest in many controlled treatment evaluation studies. Generalized linear mixed model (GLMM) procedures are widely conceived to be the preferred method of analysis for repeated measurement designs when there are missing data due to dropouts, but systematic dependence of the dropout probabilities on antecedent or concurrent factors poses a problem for testing the significance of differences in mean rates of change across time in such designs. Controlling for the dependence of dropout probabilities on baseline values poses a special problem because a theoretically correct GLMM random-effects model does not permit including the same baseline score as both covariate and dependent variable. Monte Carlo methods are used herein to evaluate the actual Type 1 error rates and power resulting from two commonly-illustrated GLMM random-effects model formulations for testing the GROUPS × TIMES linear interaction effect in group-randomized repeated measurements designs. The two GLMM model formulations differ by either including or not including baseline scores as a covariate in the attempt to control for imbalance caused by the baseline-dependent dropouts. Results from those analyses are compared with results from a simpler two-stage analysis in which dropout-weighted slope coefficients fitted separately to the available repeated measurements for each subject serve as the dependent variable for an ordinary ANCOVA test for difference in mean rates of change. The Monte Carlo results confirm modestly superior Type 1 error protection but quite superior power for the simpler two-stage analysis of dropout-weighted slope coefficients as compared with those for either of the more mathematically complex GLMM analyses.