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

作者：Koehne Voss Stephan^*; Schmidli Heinz; Smith David M; Pigeot Iris

来源：Pharmaceutical Statistics, 2011, 10(1): 45-49.

DOI：10.1002/pst.409

• 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.

• 出版日期2011-2