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RE: [NMusers] IMPMAP behavior question

From: Bill Denney <bill_at_denney.ws>
Date: Thu, 23 Aug 2018 15:05:29 -0400

Hi Bob, Leonid, and Mark,

 

Thanks for this interesting conversation! I think that it explains some =
issues with models I’d not gotten to the bottom of in the past.

 

Bob, can these timeouts be raised to the user in the main output files? =
Or even better, could the timeout be automatically raised up to some =
user-configurable fold above the default on timeout, and if it happens =
again, the model is stopped with a message “Parallel processing =
timeout, increase TIMEOUT in the .pnm file or troubleshoot lost =
calculation nodes.”

 

It seems like ignoring a subset of the data due to a timeout should not =
give results.

 

Thanks,

 

Bill

 

From: owner-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> On =
Behalf Of Bauer, Robert
Sent: Thursday, August 23, 2018 2:49 PM
To: Mark Sale <msale_at_nuventra.com>; Leonid Gibiansky =
<lgibiansky_at_quantpharm.com>; nmusers_at_globomaxnm.com
Subject: RE: [NMusers] IMPMAP behavior question

 

Mark:

You would also likely see in the .phi file that the OBJ values may be 0 =
for those subjects not collected.

 

The solution is as Leonid said, increase TIMEOUT in the pnm file.

 

Robert J. Bauer, Ph.D.

Senior Director

Pharmacometrics R&D

ICON Early Phase

820 W. Diamond Avenue

Suite 100

Gaithersburg, MD 20878

Office: (215) 616-6428

Mobile: (925) 286-0769

 <mailto:Robert.Bauer_at_iconplc.com> Robert.Bauer_at_iconplc.com

 <http://www.iconplc.com/> www.iconplc.com

 

From: owner-nmusers_at_globomaxnm.com <mailto:owner-nmusers_at_globomaxnm.com> =
 [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Mark Sale
Sent: Thursday, August 23, 2018 11:37 AM
To: Leonid Gibiansky; nmusers_at_globomaxnm.com =
<mailto:nmusers_at_globomaxnm.com>
Subject: Re: [NMusers] IMPMAP behavior question

 

thanks Leonid,

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

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

It was run parallel, and I guess that your comment about not waiting for =
all 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 to 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

 

CONFIDENTIALITY NOTICE The information in this transmittal (including =
attachments, if any) may be privileged and confidential and is intended =
only for 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 copies of the transmittal.

  _____

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com =
<mailto:lgibiansky_at_quantpharm.com> >
Sent: Thursday, August 23, 2018 11:14:51 AM
To: Mark Sale; nmusers_at_globomaxnm.com <mailto: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 =
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
> msale_at_nuventra.com <mailto:msale_at_nuventra.com%3cmsale_at_kinetigen.com> =
<msale_at_kinetigen.com>
>
> CONFIDENTIALITY NOTICE The information in this transmittal (including =
attachments, if any) may be privileged and confidential and is intended =
only for 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 copies of the transmittal.
>
>
>



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Received on Thu Aug 23 2018 - 15:05:29 EDT

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