A note on testing areas under the curve when using destructive measurement techniques.

The area under the curve of drug concentration over time is considered important in many toxicological, pharmacological, and medical investigations. In case that only one measurement for each experimental unit has been recorded, the area under the curve has to be estimated on the basis of the mean concentration values at the measurement times. Defining an estimator by using a linear combination of these mean values enables the straightforward estimation of the corresponding variance. For testing the null hypothesis of equality between two areas under the curve the use of Welch's test for nonpairwise contrasts is recommended; the previously suggested normal approximation of the test statistic is not an adequate choice since it exceeds the nominal alpha-level; this is illustrated by simulation studies.