RE: time-dependent residual error models

Hi Nick, I can't answer for Phylinda, but the general idea is to build the most appropriate structural model that is supported by data. However, after that is done, if there still is variation in residual error magnitude one should take that into account and not ignore it. All models are wrong, and I would say that in general our models for absorption are more wrong than our models for disposition. That is not just because we have focused more on the latter, but because the underlying processes governing absorption are of a different nature (e.g. with discrete events like food intake, gastric emptying, bile release and formulation disintegration and movement). Further often part of the error magnitude is from timing errors. Such errors are more pronounced when concentrations are changing fast (normally fastest changes in absorption phase). We wrote on time-varying residual errors (and alternatives such as residual error magnitude related to rate of change) in these publications: J Pharmacokinet Biopharm. 1995 Dec;23(6):651-72. J Pharmacokinet Biopharm. 1998 Apr;26(2):207-46 Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003