VPC appropriateness in complex PK

Dear NMusers: The Visual predictive check (VPC, http://www.page-meeting.org/page/page2005/PAGE2005P105.pdf , and JPKPD, Volume 35, Number 2 / April, 2008) has been touted as a useful tool for assessing the perfomance of population pharmacokinetic models. However I recently came across this abstract from the 2009 PAGE meeting: http://www.page-meeting.org/pdf_assets/4050-Standardized%20Visual%20Predictive%20Check%20in%20Model%20Evaluation%20-%20PAGE2009%20submit.pdf. This abstract states that situations when VPC is not feasible but a "Standardized Visual Predictive Check (SVPC) can be used are as follows: – Patients received individualized dose or there are a small number of patients per dose group and PK or PD is nonlinear, thus observations can not be normalized for dose – There are multiple categorical covariate effects on PK or PD parameters – Covariate is a continuous variable which made stratification impossible – Study design and execution varies among individuals, such as adaptive design, difference in dosing schedule, dose changes and dosing time varies during study, protocol violations – Different concomitant medicines and food intake among individuals when there are drug-drug interactions and food effect on PK However, the original VPC articles seem to suggest that these are the exact situations when the VPC alone is an ideal tool for model validation. Is there any justification for one approach over the other? Has anyone ever seen an SVPC utilized elsewhere, I have found nothing. Are these truly weaknesses of a VPC? Cheers! Dider