Semiparametric generalized estimating equations for repeated measurements in cross-over designs.

A model for cross-over designs with repeated measures within each period was developed. It was obtained using an extension of generalized estimating equations that includes a parametric component to model treatment effects and a non-parametric component to model time and carry-over effects; the estimation approach for the non-parametric component is based on splines. A simulation study was carried out to explore the model properties.