ADVAN 6 (cont.)

From: alison@c255.ucsf.EDU (ABoeckmann) Subject: ADVAN 6 (cont.) Date: Thu, 8 Oct 1998 08:58:21 -0700 (PDT) In response to Ingolf Meineke's note: He is correct. The maximum of 100000 evaluations of the differential equations applies to a single call to the integrating routine (a single advance of the state vector). My suggestion to use MSF's to divide the run into smaller runs probably will not help. Steve also wrote: > Sometimes it claims to have successfully converged - although when looking > at the fits this does not appear to be the case. Any ideas how to get > around this one? I responded as if he was asking what to do about a poor fit after apparently successful minimization, but he wrote back to me the following: > No, actually it was all part of the same problem (the error message occurred > just after a claim of a successful minimisation). After the Estimation Step, there are additional steps such as the Posthoc, Covariance and Table steps, and also additional passes thru the data to compute values for the output report. Evidently it was during one of these steps that the limit was reached. This would be an ideal time to have created an MSFO in the estimation step, because it could be used to complete the final steps in a later run without repeating the estimation step. Or, it may be that the posthoc step will always fail, because NONMEM is trying etas that are so far from 0 that the PK parameters are far from their population values, and the differential equations have become very ill conditioned. In that case, it may help to use the EXIT statemement to avoid totally unreasonable eta values.