Re: Reducing ETAs actually decreased OFV

On 26 August 2013 07:06, Leonid Gibiansky <[email protected]> wrote: > 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 > > > > 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:William.S.Denney@**pfizer.com <[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:lgibiansky@quantpharm.**com<[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 >> > -- Xinting