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

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