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The impact of period effects on dose level contrasts in alternating cross‐over designs for first‐time‐in‐human studies
Author(s) -
KoehneVoss Stephan,
Schmidli Heinz,
Smith David M.,
Pigeot Iris
Publication year - 2011
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.409
Subject(s) - estimator , period (music) , statistics , econometrics , computer science , mathematics , physics , acoustics
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.