The Effect of Carryover in the Estimation of Model Adjusted Means in Cross-Over Studies

Christos Stylianou

ClinBAY ltd, Cyprus

Abstract: Carryover effects constitute a potential issue when using the crossover design. Multiple methods exist, both for modelling the carryover effect, and predicting adjusted means from these models. In the current paper, we investigated the reliability of the prediction methods for estimating the model adjusted means and their differences, using a simulation study. Our simulation data suggest that the most reliable estimates were obtained when modelling the carryover effect as a factor, and assuming a carryover of zero in the predictions. However, potential confounding effects can cause large bias when using this method, and in the author’s opinion it would be preferable to completely avoid presenting the model adjusted means. Most of the methods tested, as expected, provided identical and reliable estimates of the treatment differences from these model adjusted means, when a carryover was included in the model either as factor, or using a reduced carryover model.

Keywords: Carryover effect, prediction, model adjusted means, LSMEANS, least square means, marginal means.

Pages: 109 – 122 | Full PDF Paper