RE: covariates

From: "Nick Holford" Subject: RE: [NMusers] covariates Date: Mon, September 20, 2004 2:57 pm Renee, There is something wrong with the results you have obtained. The OFV must be at least as good as the model with the power parameters fixed to their allometric theoretical values. The power parameters are very non-linear and therefore harder to estimate reliably. I suspect you are in a local minimum with Leonid's model. Try starting the model using the final parameter estimates you got from the allometric model but then let the allometric power parameters be estimated. This will ensure the fit cannot be worse than the allometric model. Question 1 -- the very small estimate of OMEGA for CL (0.000291) is suspicious (I am assuming you are using an exp(ETACL) model) and it's high uncertainty (SE 0.0626) supports this. Very small values like this suggest that the between subject variability in CL is not well defined in your data. This is very surprising as CL is usually a very robust parameter. I think there is something strange about your model/data. Question 2 -- do not worry that thed $COV step failed to run. This means nothing. Question 3 -- I don't think there is any 'right way' calculate ETA on CL. You can simply output ETA(x) or calculate TVCL*(EXP(ETA(x()-1) to do the plots against WT to look for any remaining WT effect. However, don't expect to see much unless you can fix your problem with the very low OMEGA for clearance. Note that the 'diagnostic plots' you sent are worthless in diagnosing these kinds of problem. The standard 'diagnostic plots' are not much help in deciding if you have an appropriate model. Nick Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/ _______________________________________________________