The impact of period effects on dose level contrasts in alternating cross-over designs for first-time-in-human studies
Article first published online: 8 FEB 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Volume 10, Issue 1, pages 45–49, January/February 2011
How to Cite
Koehne-Voss, S., Schmidli, H., Smith, D. M. and Pigeot, I. (2011), The impact of period effects on dose level contrasts in alternating cross-over designs for first-time-in-human studies. Pharmaceut. Statist., 10: 45–49. doi: 10.1002/pst.409
- Issue published online: 8 FEB 2010
- Article first published online: 8 FEB 2010
- Manuscript Accepted: 30 NOV 2009
- Manuscript Revised: 18 SEP 2009
- Manuscript Received: 3 NOV 2008
- cross-over trial;
- first-time-in-human study;
- period effects
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. Copyright © 2010 John Wiley & Sons, Ltd.