From: Daniel Corrado <daniel_corrado@yahoo.com> Subject: [NMusers] Parameter %RSE vs ETA %RSE Date: 7/17/2003 1:57 PM The results of my Nonmem modeling of a sparse data set are given below * 1 comp model with CL, V and Ka * Successful minimization * Covariance matrix obtained * goot obs vs pred and obs vs ipred plots THETA1 = CL = 1.66e+003; %RSE = 3.2% THETA2 = V = 2.04e+003; %RSE = 32.9% THETA3 = KA = 0.196; %RSE = 10.4% Errors ETA1 = 0.0230; %RSE= 65.2% (CI bound zero) ETA2=1.36; %RSE = 39.1% ETA3=6.70e-008; %RSE 1.37e+008%(CI bound zero) A colleague of mine indicated that the large %RSE associated with ETA3 indicats that ETA3 and by association THETA3(KA) estimations were not very good. He suggested that I fix KA prior to modeling and try to estimate only CL and V. My contention is that the value of KA obtained is in the ball park of that seen from dense data studies. Also %RSE associated with THETA3 is small. The value of ETA3 is so small that the high %RSE associated with it still makes it insignificant when compared to THETA3. Also the %CV for ETA 3 = 0.03% despite the large %RSE. Hence the value of KA and ETA3 are ok. Could someone let me know if my line of reasoning if totally off. Thanks, Dan _______________________________________________________ From: Leonid Gibiansky <lgibiansky@emmes.com> Subject: Re: [NMusers] Parameter %RSE vs ETA %RSE Date: 7/17/2003 2:28 PM You should remove eta3 from the model since it is so small (effectively, zero). You will not see any difference in OF or fit. Your eta1 is also rather small, and has large RSE. After you remove eta3, try to remove eta1 as well, you may found out that there is no difference (with the original model) either. One the other hand, eta2 is too large (do you use V=THETA(2) * EXP(ETA(2)) model ?). Try to use FOCE and study distribution of eta2: variance of eta2 is too large to accept the model without trying to find a better model or an explanation why this variance is so large. Good luck Leonid _______________________________________________________ From: Sam Liao <sliao@pharmaxresearch.com> Subject: RE: [NMusers] Parameter %RSE vs ETA %RSE Date: 7/17/2003 3:50 PM Hi Daniel: Based on CL and V estimates, the elimination half-life is 0.85 hr while the absorption half-life is 3.5 hours. How is this compared with those half-lives obtained from intensive PK sampling? If there is a flip-flop, V estimate will be affected too. It may be a good ideal to fix KA to avoid flip-flop, if the sparse data do not have enough data in the absorption phase. Best regards, Sam Liao _______________________________________________________