An alternative index for assessing profile similarity in bioequivalence trials.
In a typical bioequivalence trial, summary measures of the plasma concentration versus time profile are used to compare two formulations of a drug product. Commonly used measures include area under the curve (AUC), maximum plasma concentration (C(max)) and time to maximum concentration (T(max)). Equivalence of these summary measures, in general, does not guarantee equivalence of the entire profile. Rescigno and Chinchilli and Elswick propose indices which measure profile similarity, but can be overly sensitive to unimportant differences and are not easily interpreted pharmacologically. We propose an alternative index based on smoothing the relative difference between bioavailability profiles. This provides a method for assessing bioequivalence over the entire profile which has a familiar interpretation and can be tuned to provide a compromise between the insensitivity to pattern differences of summary measures and the oversensitivity of pointwise comparisons.
Mauger
D T
DT
The Pennsylvania State University, Department of Health Evaluation Sciences, H173, 500 University Drive, Hershey, PA 17033, USA. dmauger@psu.edu
Chinchilli
V M
VM
D019540:Area Under Curve; D006801:Humans; D015233:Models, Statistical; D013810:Therapeutic Equivalency