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
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
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
Freundliche Grüße / Best regards,
Head Quantitative Pharmacology
Bayer Pharma Aktiengesellschaft
BPH-DD-CS-CP-QP, Quantitative Pharmacology
Building 0431, 322
51368 Leverkusen, Germany
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