RE: Describing variability

From: "Justin Wilkins" Subject:RE: [NMusers] Describing variability Date:Mon, 31 Mar 2003 10:47:14 +0200 Dear Nick, Atul, and NMusers... Thanks for the feedback. I incorporated the approach used the the Karlsson & Sheiner paper. Some questions arising from what you've suggested: 1) Why would FOCE be better? It's worth pointing out that one group of patients was made up of a large cohort sampled sparsely (3x daily, at random times) on multiple occasions - would this rock the boat, so to speak? When running a FOCE analysis on the rich patient group, it takes a great deal longer and invariably generates errors (MINIMIZATION TERMINATED DUE TO PROXIMITY OF LAST ITERATION EST. TO A VALUE AT WHICH THE OBJ. FUNC. IS INFINITE (ERROR=136)), even using a higher value for SIGDIGITS, the conditional statements suggested by Alison Boeckmann in this list added to $PK and making adjustments to NSIZES and TSIZES. Also, generated parameter estimates for CL, V and KA are markedly larger than those generated by a plain FO run. 2) When pooling groups, different sampling strategies were used since a lot of it is retrospective and not designed specifically for this study. How should I deal with occasion specification, considering that (all told) there are about 15 different sampling dates across the group? 3) Finally, why use the SAME constraint in the ETA initial estimates for all but the first occasion? The Karlsson & Sheiner paper wasn't clear on that point, and it seems to suggest that the assumption is being made that IOV is constant across all occasions. Thanks for the help so far! Justin