Analysing pharmacokinetic drug interaction or comparability studies with missing values in crossover design

Abstract

In a pharmacokinetic drug interaction study using a three‐period, three‐treatment (drug A, drug B, and drugs A and B concomitantly) crossover design, pharmacokinetic parameters for either drug are only measured in two of the three periods. Similar missing data problems can arise for a four‐period, four‐treatment crossover pharmacokinetic comparability study. This paper investigates whether the usual ANOVA model for the crossover design can be applied under this pattern of missing data. It is shown that the model can still be used, contrary to a belief that a new one is needed. The effect of this type of missing data pattern on the statistical properties of treatment, period and carryover effect estimates was derived and illustrated by means of simulations and an example. Copyright © 2003 John Wiley & Sons, Ltd.