RE: VPC results using PsN and Xpose

All, I think Leonid and Neil have pointed out two plausible explanations, I just wanted to highlight that these are two separate issues: * If you have an additive component in your error model a graph on log scale would appear to widen at the end. This is fine. In this particular case since observations also widen at the end this may be a likely explanation, with the limited information nmusers have * If you have implemented a translation of proportional + additive on the log scale; this is only an approximation and in particular for simulations it may fall over. This occurs when IPRED is VERY close to zero. Typically this occurs around the time when drug is first absorbed (e.g. towards the end of lag time), but if you have rapid elimination I guess it can happen at the end of the time interval. This error model is not suitable when IPRED is very small, and then issue only appears during simulation. As a result, one may simulate odd observations with concentrations towards the infinite at the time of lag. If this is affecting you VPC you certainly need to deal with it and one solution would be to change your error model, as Neil suggests. As an alternative, putting a very low cutoff to the IPRED used in weighting the error would help. Since the cutoff is very low it will not affect estimation, but will remove unreasonable values during simulation. Best regards Jakob