Mark,

IMPMAP procedure produces run.cnv file. There you can find mean and SD of OF (over the last few iterations that were considered for convergence stop). I use these numbers for covariate assessment as iteration-to-iteration numbers oscillate and cannot be reliably compared.

Concerning the last iteration OF drop, cannot tell for sure but I've seen OF drops in some cases when the main manager do not wait for the slaves to return OF of their portion of the data. prn file has parameters TIMEOUTI and TIMEOUT, and I would try to increase them and see whether this fixes the problem

Thanks
Leonid




On 8/23/2018 1:54 PM, Mark Sale wrote:
I have a model that seems to be behaving strangely, looking for interpretation 
help


in model building, the OBJ is usually ~20900. Until this model, where, on the 
covariance step (IMPMAP method) the OBJ drops 9000  points (20798 to 11837), 
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 
good), p values for ETAs are very reasonable, it converges, condition # is 
good. Only two issues:
RSE for 2 OMEGAs is a little large (0.5)
an interoccasion variability term (on V) is very large (~4, exponential). This 
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 on 
CL, to address the issue with SS data, cannot identify Volume uniquely (using 
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 essentially the 
same parameter estimates. So I end up rejected all additional covariates in 
this model  (at least by LRT).


other details, running on Windows, 64 bit, Intel compiler, NONMEM version 7.3.


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?

thanks



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

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