Re: OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS
Hi Jules,
it seems that your two ETAs are heavily correlated (1.00) and this causes
problems for NONMEM. Next to evaluating if you really need two destinct
ETAs or should use just one as in e.g.
E0= THETA(1)*EXP(ETA(1))
EMAX = E0+THETA(2)
I would suggest to re-code your Emax and E0 in logit space if you are
trying to model a DV that is between 0 and 1.
E0 = EXP(THETA(1) + ETA(1))/(1+EXP(THETA(1)+ETA(1))
EMAX =
EXP(THETA(1)+THETA(2)+ETA(1)+ETA(2))/(1+EXP(THETA(1)+THETA(2)+ETA(1)+ETA(2)))
again check if ETA(2) (or ETA(1)) is really necessary. THETA(2) should be
positive in all examples.
Kind Regards
Sven Mensing
Quoted reply history
2013/9/17 Jules Heuberger <[email protected]>
> 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]*
> http://www.chdr.nl**
>
> *[image: CHDR_logo_verticaal_onderregel_fc_positief.jpg]***
>