Combined residual model and IWRES.

Dear All, I'm working on a one-compartment iv model. I have used a model for the IWRES from a discussion from May 2001 (thanks to Mats Karlsson, Niclas Jonsson and Nick Holford), where you use thetas to obtain the sigmas when using a combined residual model: IPRED=F IRES=DV-IPRED IWRES=(DV-IPRED)/SQRT(F*F*THETA(3)*THETA(3)+THETA(4)*THETA(4)) Y=F*(1+THETA(3)*ERR(1))+THETA(4)*ERR(2). where you then fix the sigmas to 1. I obtained the following results for a particular base model: ETA = 3.16 28.1 0.0804 0.163 ETASD = 1.23693 1.42478 ERRSD = 1 1 THETA:se% = 23.9 32.0 39.9 23.3 OMEGA:se% = 18.4 33.8 SIGMA:se% = 0.0 0.0 I then ran the same model but using the normal code in the $ERROR section to see if there was any difference in the final estimates: IPRED=F IRES=DV-IPRED Y=F*(1+ERR(1))+ERR(2) and obtained these results: THETA = 3.16 28.1 ETASD = 1.23693 1.42478 ERRSD = 0.0803741 0.163095 THETA:se% = 23.5 32.0 OMEGA:se% = 18.5 33.9 SIGMA:se% = 79.3 45.9 Here are few questions: 1.Can anyone tell me why the standard errors for the thetas in model 1 and the standard errors for the sigmas in model 2 differ so significantly? 2.Why does the algorithm used to obtain the standard errors for the sigmas differ so much from that used to obtain standard errors for the thetas, and how? 3.What are the implications when then using INTERACTION? 4....and finally, which model should i use? Thankyou in advance for any light that can be shed. Best, Paul Westwood.