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Keywords:

  • dose response study;
  • pharmacokinetic parameters;
  • Mahalanobis distance;
  • heteroscedastic variance;
  • sample size calculation

Abstract

Dose proportionality/linearity is a desirable property in pharmacokinetic studies. Various methods have been proposed for its assessment. When dose proportionality is not established, it is of interest to evaluate the degree of departure from dose linearity. In this paper, we propose a measure of departure from dose linearity and derive an asymptotic test under a repeated measures incomplete block design using a slope approach. Simulation studies show that the proposed method has a satisfactory small sample performance in terms of size and power. Copyright © 2010 John Wiley & Sons, Ltd.