Multivariate linear mixed models for multiple outcomes.

We propose a multivariate linear mixed (MLMM) for the analysis of multiple outcomes, which generalizes the latent variable model of Sammel and Ryan. The proposed model assumes a flexible correlation structure among the multiple outcomes, and allows a global test of the impact of exposure across outcomes. In contrast to the Sammel-Ryan model, the MLMM separates the mean and correlation parameters so that the mean estimation will remain reasonably robust even if the correlation is misspecified. The model is applied to birth defects data, where continuous data on the size of infants who were exposed to anticonvulsant medications in utero are compared to controls.