The impact of period effects on dose level contrasts in alternating cross-over designs for first-time-in-human studies.

Abstract

For first-time-in-human studies with small molecules alternating cross-over designs are often employed and at study end are analyzed using linear models. We discuss the impact of including a period effect in the model on the precision with which dose level contrasts can be estimated and quantify the bias of least squares estimators if a period effect is inherent in the data that is not accounted for in the model. We also propose two alternative designs that allow a more precise estimation of dose level contrasts compared with the standard design when period effects are included in the model.

DOI: 10.1002/pst.409

Cite this paper

@article{KoehneVoss2011TheIO, title={The impact of period effects on dose level contrasts in alternating cross-over designs for first-time-in-human studies.}, author={Stephan Koehne-Voss and Heinz Schmidli and David M. Smith and Iris Pigeot}, journal={Pharmaceutical statistics}, year={2011}, volume={10 1}, pages={45-9} }