NONMEM Users Network Archive

Hosted by Cognigen

Re: [NMusers] IMPMAP behavior question

From: Mark Sale <msale_at_nuventra.com>
Date: Thu, 23 Aug 2018 18:36:40 +0000

thanks Leonid,

I looked at that, and ossilation/sampling doesn't seem to be the issue, mea=
n was 20804.0136597062, SD = 2.19872089635881.

And the OBJ is very stable in the minimzation part, up until the last itera=
tion/covariance iteration.

It was run parallel, and I guess that your comment about not waiting for al=
l the workers concerns me. There is a timeout event in the log file:

ITERATION 70
 STARTING SUBJECTS 1 TO 8 ON MANAGER: OK
 STARTING SUBJECTS 9 TO 17 ON WORKER1: OK
 STARTING SUBJECTS 18 TO 32 ON WORKER2: OK
 STARTING SUBJECTS 33 TO 85 ON WORKER3: OK
 COLLECTING SUBJECTS 1 TO 8 ON MANAGER
 COLLECTING SUBJECTS 18 TO 32 ON WORKER2
 COLLECTING SUBJECTS 9 TO 17 ON WORKER1
 COLLECTING SUBJECTS 33 TO 85 ON WORKER3
 ITERATION 70
 STARTING SUBJECTS 1 TO 8 ON MANAGER: OK
 STARTING SUBJECTS 9 TO 17 ON WORKER1: OK
 STARTING SUBJECTS 18 TO 32 ON WORKER2: OK
 STARTING SUBJECTS 33 TO 85 ON WORKER3: OK
 COLLECTING SUBJECTS 1 TO 8 ON MANAGER
 TIMEOUT FROM WORKER1
 RESUBMITTING JOB TO LOCAL
 STARTING SUBJECTS 9 TO 17 ON MANAGER: OK
 COLLECTING SUBJECTS 18 TO 32 ON WORKER2

and no mention of collecting subjects 33 to 85 on worker 3, or subjects 9 t=
o 17 on worker 1.

so, that could be the problem.
Bob - thoughts?





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

CONFIDENTIALITY NOTICE The information in this transmittal (including attac=
hments, if any) may be privileged and confidential and is intended only for=
 the recipient(s) listed above. Any review, use, disclosure, distribution o=
r copying of this transmittal, in any form, is prohibited except by or on b=
ehalf of the intended recipient(s). If you have received this transmittal i=
n error, please notify me immediately by reply email and destroy all copies=
 of the transmittal.
________________________________
From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Sent: Thursday, August 23, 2018 11:14:51 AM
To: Mark Sale; nmusers_at_globomaxnm.com
Subject: Re: [NMusers] IMPMAP behavior question

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 interpret=
ation 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 1=
1837), 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 es=
sentially 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 t=
he 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
> msale_at_nuventra.com<msale_at_kinetigen.com>
>
> CONFIDENTIALITY NOTICE The information in this transmittal (including att=
achments, if any) may be privileged and confidential and is intended only f=
or the recipient(s) listed above. Any review, use, disclosure, distribution=
 or copying of this transmittal, in any form, is prohibited except by or on=
 behalf of the intended recipient(s). If you have received this transmittal=
 in error, please notify me immediately by reply email and destroy all copi=
es of the transmittal.
>
>
>



Received on Thu Aug 23 2018 - 14:36:40 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request_at_iconplc.com. Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.