Re: Reducing ETAs actually decreased OFV
Hi Xinting,
You should be able to do it. Let's check it again this way
1. You run the model with all ETAs included, but one ETA (the one that was excluded in the reduced model) is fixed to zero. You should be able to reproduce your "reduced ETA" result (OF) 2. You take the same control stream, and set all initial values to the final parameter estimates of model (1) above, except you use the small value (may be not 0.01 but 0.000001) as the initial value of the ETA that was fixed to zero in model (1).
Model (2) is the not-reduced model, and it's OF should be less or equal to the OF of model (1). If this is not the case, increase the number of significant digits in the initial estimates of model (2) - take those from the final estimates of model 1.
Without data, it is very difficult to offer more specific advice.
Also, what is the magnitude of the OF change? What is the estimate of the OMEGA for the ETA in question?
Regards,
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 8/25/2013 8:42 AM, Xinting Wang wrote:
> Dear Leonid,
>
> I tried with your method and found the same result. The initial
> estimation of the added ETA was set at 0.01, and the result showed an
> increase of OFV. Please see below the $PK part of the control file for
> more information. Many thanks.
>
> Dear Bill,
>
> Could you please explain that in a little bit more detail? I am pasting
> the $PK part of the control file in case you could find the useful
> information. Thanks a lot.
>
> $PK
>
> FA1=0
> FA2=0
> FA3=0
> FA4=0
>
> IF(DOSE.EQ.250) THEN
> FA1=1
> ENDIF
>
> IF(DOSE.EQ.500) THEN
> FA2=1
> ENDIF
>
> IF(DOSE.EQ.850) THEN
> FA3=1
> ENDIF
>
> IF(DOSE.EQ.1000) THEN
> FA4=1
> ENDIF
>
> F1=FA1+FA2*THETA(6)+FA3*THETA(7)+FA4*THETA(8)
>
> TVCL=THETA(1)
> TVV2=THETA(2)
> TVKA=THETA(3)
> TVQ=THETA(4)
> TVV3=THETA(5)
>
> CL=TVCL*EXP(ETA(1))
> V2=TVV2*EXP(ETA(2))
> KA=TVKA*EXP(ETA(5))
> Q=TVQ*EXP(ETA(3))
> V3=TVV3*EXP(ETA(4))
>
> S2=V2/1000
> S3=V3/1000
>
> $ERROR
>
> IPRE=F
>
> IRES=DV-IPRE
>
> W=F
>
> IF(W.EQ.0) W = 1
>
> IWRE = IRES/W
>
> Y=F*(1+EPS(1))+EPS(2)
>
> Best Regards
>
> On 12 August 2013 20:50, Denney, William S. <[email protected]
> <mailto:[email protected]>> wrote:
>
> Hi Xinting,
>
> In a few rare cases, I've seen this happen if the model is
> approaching nonconvergence. In those cases, typically the RSE on
> one or more parameters will increase and the ratio of max to min
> eigenvalues will increase substantially. Are you seeing either of
> these?
>
> Thanks,
>
> Bill
>
> On Aug 11, 2013, at 21:56, "Leonid Gibiansky"
> <[email protected] <mailto:[email protected]>> wrote:
>
> Xinting,
> Try to start from the initial conditions of your "reduced" model but
> add that "reduced" ETA with the corresponding OMEGA equal to 0.01 or
> other small number. If the control stream code is correct, the
> objective function should decrease or retain the same value.
> Leonid
>
> --------------------------------------
> Leonid Gibiansky, Ph.D.
> President, QuantPharm LLC
> web: www.quantpharm.com http://www.quantpharm.com
> e-mail: LGibiansky at quantpharm.com http://quantpharm.com
> tel: (301) 767 5566 <tel:%28301%29%20767%205566>
>
> On 8/10/2013 10:23 PM, Xinting Wang wrote:
> > Dear all,
> >
> > Does anyone witnessed such a phenomenon in NONMEM as when you
> reduced an
> > ETA, the OFV value, rather than increase, actually decreased?
> It's quite
> > against intuition, as individual estimation should be better than
> > population estimation in that particular parameter. Both models,
> whether
> > having this ETA, converged very well.
> >
> > Best
> >
> > --
> > Xinting
>
> --
> Xinting