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IMPMAP behavior question

From: Mark Sale <msale>
Date: Thu, 23 Aug 2018 17:54:13 +0000

I have a model that seems to be behaving strangely, looking for interpretat=
ion help

in model building, the OBJ is usually ~20900. Until this model, where, on t=
he covariance step (IMPMAP method) the OBJ drops 9000 points (20798 to 118=
37), monitoring from output file below

iteration 70 OBJ= 20798.6782833867 eff.= 5530. Smpl.= =
  10000. Fit.= 0.99524
 Convergence achieved
 iteration 70 OBJ= 11837.9045704476 eff.= 5475. Smpl.==
   10000. Fit.= 0.99522

Parameters don't change much (edited .ext file below).

50 1.35E+01 9.96E-01 4.42E-02 9.41E-01 3.05E+01 1.29E-01 20799.68932
60 1.35E+01 9.67E-01 4.45E-02 9.43E-01 3.05E+01 1.29E-01 20792.90665
70 1.35E+01 9.73E-01 4.44E-02 9.44E-01 3.05E+01 1.29E-01 20798.67828
70 1.35E+01 9.73E-01 4.44E-02 9.44E-01 3.05E+01 1.29E-01 11837.90457

Plots don't look particularly different than other model (and look pretty g=
ood), p values for ETAs are very reasonable, it converges, condition # is g=
ood. Only two issues:
RSE for 2 OMEGAs is a little large (0.5)
an interoccasion variability term (on V) is very large (~4, exponential). T=
his is, I think, related to many subjects with data only at steady state.

Further, when I advance this model, add another covariate, or another IOV o=
n CL, to address the issue with SS data, cannot identify Volume uniquely (u=
sing the final parameter from this model as the initial in the next model),=
 I cannot reproduce these results - the OBJ goes back to ~20,800, with esse=
ntially the same parameter estimates. So I end up rejected all additional c=
ovariates in this model (at least by LRT).

other details, running on Windows, 64 bit, Intel compiler, NONMEM version 7=

Can I believe this OBJ value? Should I base an additional hypotheses on the=
 SEE, rather than the LRT?

But, basically, why is this happening?


Mark Sale M.D.
Senior Vice President, Pharmacometrics
Nuventra Pharma Sciences, Inc.
2525 Meridian Parkway, Suite 200
Durham, NC 27713
Phone (919)-973-0383

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Received on Thu Aug 23 2018 - 13:54:13 EDT

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