RE: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS

From: Doug J. Eleveld Date: September 17, 2013 technical Source: mail-archive.com
Hi Jules, If the correlation between two ETAs is 0 then you should be able to remove one ETA and replace it by a scaled version of the other ETA and get the same objective function value. This model would not have a correlation problem (since only one ETA) so your problem would be "solved" in a superficial way. Of course you might not be satisfied with the idea that one of your ETAs is (except for scale) wholly determined by the ETA for a different paramater with a different physical interpretation. What reason might be that these paramaters are so strongly related in your data? I think that usually this suggests that the model is too complex for the information available in the dataset. Or maybe some other model structure would be better. Douglas Eleveld ________________________________
Quoted reply history
Van: [email protected] [mailto:[email protected]] Namens Jules Heuberger Verzonden: September 17, 2013 12:42 PM Aan: [email protected] Onderwerp: [NMusers] OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS Dear NM Users, I ran into a problem with a NM 7.2 run with an OMEGA BLOCK (2), receiving an error message saying the parameter estimate is near its boundary (See also the discussion in [NMusers] How to solve it? ERROR: PARAMETER ESTIMATE IS NEAR ITS BOUNDARY ). After digging through the documentation I am still unsure where the problem is originating from. What I figured out is that the problem lies in the OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS *******, a matrix I believe is only introduced since NM7.2. The estimate in this matrix that is giving problems is the one for the OMEGA BLOCK, which is estimated to be 1 (a boundary). Now, as far as I know, the OMEGA - CORR MATRIX is related to the OMEGA - COV MATRIX as the sqrt of its estimate. However, it is unclear to me how the OMEGA BLOCK estimate (COV MATRIX), which gives the correlation between the two ETAs, is related to the OMEGA - CORR MATRIX value. What does this value actually mean, and what does it mean for my error message, as the correlation estimate itself seems to be fine? In the print below you can see the model and resulting estimates, the important ones being 5.26E-02 (OMEGA - COV MATRIX of ETA1-ETA2) and 1.00E+00 (OMEGA - CORR MATRIX of ETA1-ETA2). The model has two ETAs and an proportional error model, Thanks in advance for any insights and help, Best, Jules Heuberger $SUB ADVAN=6 TOL=5 $MODEL COMP=(CENTRAL) COMP=(PERI) $PK ; structural model K10=IK10 V1 =IV1 K12=EXP(-1.29) K21=EXP(-0.63) V2=K12*V1/K21 BSL=IBSL E0=THETA(1)*EXP(ETA(1)) EMAX=THETA(2)*EXP(ETA(2)) EC50=THETA(3) ; $DES DADT(1) = -K10*A(1)-K12*A(1)+K21*A(2) DADT(2) = K12*A(1)-K21*A(2) $ERROR CP=F EFF=E0-EMAX*F/(EC50+F) Y= EFF*(1+ERR(1))+ERR(2) IPRE=EFF $THETA 55 20.9 364 ; $OMEGA BLOCK(2) 0.2 0.01 0.2 $SIGMA 0.01 0 FIX $EST PRINT=5 MAX=9999 METHOD=1 INTERACTION POSTHOC NOABORT MSFO=mfi __________________________________________________________ OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS ******** ETA1 ETA2 ETA1 + 2.44E-02 ETA2 + 5.26E-02 1.13E-01 SIGMA - COV MATRIX FOR RANDOM EFFECTS - EPSILONS **** EPS1 EPS2 EPS1 + 1.11E-02 EPS2 + 0.00E+00 0.00E+00 1 OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS ******* ETA1 ETA2 ETA1 + 1.56E-01 ETA2 + 1.00E+00 3.37E-01 SIGMA - CORR MATRIX FOR RANDOM EFFECTS - EPSILONS *** EPS1 EPS2 EPS1 + 1.05E-01 EPS2 + 0.00E+00 0.00E+00 Jules Heuberger Clinical Scientist Centre for Human Drug Research Zernikedreef 8 2333 CL Leiden The Netherlands '+31 (0)71 5246400 (+31 (0)6 43937461 7+31 (0)71 5246499 [email protected]<mailto:[email protected]> http://www.chdr.nl/ [CHDR_logo_verticaal_onderregel_fc_positief.jpg] ________________________________
Sep 17, 2013 Jules Heuberger OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Sep 17, 2013 Sven Mensing Re: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Sep 17, 2013 Paolo Denti Re: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Sep 17, 2013 Doug J. Eleveld RE: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Sep 17, 2013 Jakob Ribbing RE: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Sep 17, 2013 Jeroen Elassaiss-Schaap RE: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS