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AW: AW: [NMusers] IMP and parallelisation

From: Dirk Garmann <dirk.garmann_at_bayer.com>
Date: Fri, 23 Sep 2016 07:47:52 +0000

Dear all,
Meanwhile we further investigated the issue. We might need some information=
 and advice from Robert Bauer

Two issues have been identified.

->MH sampling in general -> leads to some instability in the OBF if more no=
des are used
->More important: the use of a sigma as proposed in NONMEM 7.3.0:-.

.......---- SIGMA(x,x) has been allowed to be used on the right hand side o=
f equations in the control stream file. In this model, we followed the reco=
mmendation for BLQ values by designating the GRD appropriately:.
$EST METHOD=IMP LAPLACE INTERACTION CTYPE=3 NOHABORT GRD=SN(1) PRINT=
=1

In the test cases this leads to different OBF in case of parallelization's =
(in the first iterations in some models OBF drastically increase) independe=
nt of the use of parse_type=1 und ranmethod=p..
For further investigations, we would need the exact implementation in NONME=
M. For the moment we will stay away from using Sigma on the right hand side=
 with IMP and BLQ values.
Any information and advice would be highly appreciated

Best wishes
Dirk




-----Ursprüngliche Nachricht-----
Von: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] Im =
Auftrag von Dirk Garmann
Gesendet: Dienstag, 20. September 2016 20:05
An: Leonid Gibiansky; nmusers_at_globomaxnm.com
Betreff: AW: AW: [NMusers] IMP and parallelisation


Dear Leonid

Still in the evaluation phase. I thought it was already finished but still =
running (long run times). I will keep you informed if the results are ident=
ical

Best
Dirk

 




-----Ursprüngliche Nachricht-----
Von: Leonid Gibiansky [mailto:lgibiansky_at_quantpharm.com]
Gesendet: Dienstag, 20. September 2016 15:54
An: Dirk Garmann; nmusers_at_globomaxnm.com
Betreff: Re: AW: [NMusers] IMP and parallelisation

Hi Dirk,
What do you mean "does not solve the issue"? Were the results identical
with different number of nodes or not?
Thanks
Leonid

On 9/20/2016 9:47 AM, Dirk Garmann wrote:
> Thank you Leonid,
> We have tried RANMETHOD=P, which is an interesting possibility.
> Unfortunately this does not solve the issue. We will further evaluate if =
the information from all nodes is used for the population update.
> Any further hints are highly welcome
>
>
> Best
> Dirk
>
> -----Ursprüngliche Nachricht-----
> Von: Leonid Gibiansky [mailto:lgibiansky_at_quantpharm.com]
> Gesendet: Montag, 19. September 2016 22:26
> An: Dirk Garmann; nmusers_at_globomaxnm.com
> Betreff: Re: [NMusers] IMP and parallelisation
>
> It is a good idea to use RANMETHOD=P at estimation step; then the
> results should be identical independently of the number of nodes and
> computer load.
>
> Concerning specific behavior .. looks strange. I would try to start from
> the initial values of the model with the lowest OF and see what happens.
>
> Thanks
> Leonid
>
>
> On 9/19/2016 1:29 PM, Dirk Garmann wrote:
>> Dear nmusers.
>>
>> During a popPK analysis using the M3 method and IMP we observed an
>> unexpected behavior and would be interested if anyone else observed the
>> same and can provide guidance/explanations.
>>
>>
>>
>> The IMP produces "strange" results in cases requiring a parallelization.
>>
>> We observed a general (and strong) trend that with increasing number
>> of nodes the OBF increases (!) which in my opinion is unexpected if the
>> number of samples in MC is sufficiently large.
>>
>>
>>
>> The initial settings have been as follows:
>>
>> Parse Type 1
>>
>>
>>
>> $EST METHOD=IMP INTERACTION LAPLACIAN EONLY=0 ISAMPLE=300 NITER==
1000
>> CTYPE=3 NOABORT GRD=SN(1,2) NOTHETABOUNDTEST PRINT=1
>>
>> $EST METHOD=IMP INTERACTION NOABORT GRD=SN(1,2) EONLY=1 ISAMPLE==
3000
>> NITER=30 PRINT=1
>>
>>
>>
>> With 1 node the OBF decreased to ~- 1400
>>
>> Using 16 nodes the OBF stabilized at ~ 1000
>>
>> In both cases the OBF does not fluctuate much after 100 interations
>> (monitoring of EM step) and seems to be stable (no clear hint for a
>> local minima).
>>
>> Interestingly the estimated residual error is higher using 1 node. With
>> 16 nodes the variability seems to be shifted to the ETAS.
>>
>>
>>
>> This behavior might be a concern for a covariate analysis using IMP
>>
>> Our first assumption was that we need to increase iSAMPLE in the EM
>> step, since a different seed might be used for each node. However even
>> increasing ISAMPLE to 3000 in the first step did not change the results
>> much.
>>
>> My guess is that it points in the direction of how population values are
>> updated, but I am not an expert in the implementation of IMP in NONMEM
>>
>>
>>
>> We would be highly interested in any guidance and explanation.
>>
>>
>>
>> Many thanks in advance
>>
>>
>>
>> Dirk
>>
>>
>>
>> Freundliche Grüße / Best regards,
>>
>>
>>
>> Dirk Garmann
>>
>> Head Quantitative Pharmacology
>>
>>
>>
>>
>>
>> Bayer Pharma Aktiengesellschaft
>>
>> BPH-DD-CS-CP-QP, Quantitative Pharmacology
>>
>> Building 0431, 322
>>
>> 51368 Leverkusen, Germany
>>
>>
>>
>> Tel: +49 202 365577
>>
>> Fax:
>>
>> Mobile: +49 175 3109407
>>
>> E-mail: _dirk.garmann_at_bayer.com_
>>
>> Web: _http://www.bayer.com_
>>
>>
>>
>> Vorstand: Dieter Weinand, Vorsitzender | Christoph Bertram
>>
>> Vorsitzender des Aufsichtsrats: Hartmut Klusik
>>
>> Sitz der Gesellschaft: Berlin | Amtsgericht Charlottenburg, HRB 283 B
>>
>>
>>
>>
>>
>>
>>
>
Received on Fri Sep 23 2016 - 03:47:52 EDT

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