TL44: Modeling the dissimilarities of Test-Reference concentration curves in post-marketing safety/ surveillance studies of generic drugs
*Elena Rantou, FDA/CDER 


"In an attempt to model the differences of the plasma concentration curves of the Test and Reference formulations in a post-marketing safety/ surveillance study of a generic drug, there are numerous issues to be addressed as the presence of outliers and the critical concentration times. Critical times can be characterized as the ones that determine either the maximum separation or the highest similarity between the two curves. The choice of the appropriate statistical approach to detect critical times should depend on the distributional properties of the data, the variance/ covariance structure and the fact that concentration times are not equally spaced. These lead to the modification of some similarity measures in such a way that are sensitive to changes between consecutive times. In addition, we can construct an acceptance region of the difference Test-Reference, at specific time points. If the above techniques can be standardized so that they yield comparable results from different studies, they can be extended to comparing two or more generic drugs. "