Bioequivalence and Bioavailability Forum

Hi d_labes,

❝ But carry-over evaluation in cross-over designs, if any, suffer from another fact. It is usually modeled as so called "first order" carry-over or "simple carry over". The main feature of such modeling is that the carry-over effect lasts only from the treatment given in the previous period.

❝ This model is extremely oversimplified and not in accordance with pharmacokinetic and pharmacodynamic conceptions. (see Steven Senn, Cross-over Trials in Clinical Research, John Wiley & Sons, Chichester, chapter 10)

Has it ever been shown that this is not merely a theoretical problem? I understand why first order is not any order but really, is there an issue of practical importance here?