Hi Xinting, When I've seen this before, it is due to the model approaching non-convergence. Given the model that you're showing below, I'd guess that your issue is coming from the eta on Q or V3 because it is rare to have enough data to fit true IIV there.
Thanks, Bill On Aug 25, 2013, at 8:42, "Xinting Wang" <wxinting1...@gmail.com<mailto:wxinting1...@gmail.com>> 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. <william.s.den...@pfizer.com<mailto:william.s.den...@pfizer.com>> 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" <lgibian...@quantpharm.com<mailto:lgibian...@quantpharm.com>> 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
