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From: Sam Liao <sliao>
Date: Mon, 26 Oct 2009 11:36:02 -0400

Dear NONMEM team:

I have two nm7 questions.


I have a PKPD model using ADVAN13 to solve the ODE. It took 12 hours to
complete the $EST step with rounding error.

But it's been over 15 hours running the $COV step with UNCONDITIONAL option.


This is much longer time than I expected. Could this be an infinitive loop?
Should I interrupt the run and try smaller SIGL in $COV? I tried the CTL-K
or CTL-E to exit, but it did not work for me.


The second question related to BAYES method in $EST step. The model run
successfully using FOCE method. But when I tried the BAYES method with
NOABORT option, it terminated with 'OBJECTIVE FUNCTION IS INFINITE' in
Burn-in mode after 10 iterations. The statement used as below. How can I
get around this problem?





Best regards,



From: owner-nmusers
Behalf Of Bauer, Robert
Sent: Sunday, October 25, 2009 11:29 PM
To: nonmem
Subject: RE: [NMusers] method=ITS, OPTIMIZATION NOT TESTED (?!)



The objective function progress looks good. You should expect some Monte
Carlo fluctuations. You should also run more iterations (perhaps
NITER=200), and set CTYPE=3, which turns on the termination tester. To
resume where you left off, rename your new control stream file, and put in
the following lines.


$EST METHOD=CHAIN NSAMPLE=0 ISAMPLE=50 FILE=my_old_control_stream_file.ext

$EST METHOD=IMP NITER=200 CTYPE=3 FILE=my_new_control_stream_file.ext


Make sure you are linear MU referencing to get the greatest efficiency.



Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics
ICON Development Solutions

Tel: (215) 616-6428
Mob: (925) 286-0769
Email: <mailto:Robert.Bauer






From: owner-nmusers
Behalf Of nonmem
Sent: Saturday, October 24, 2009 8:03 PM
To: nmusers
Subject: [NMusers] method=ITS, OPTIMIZATION NOT TESTED (?!)

Hello NONMEM Team,

I found method=imp useful when there are local maxima. Nevertheless, at the
end of optimization it prints a message, which makes me feel somewhat
uncomfortable: OPTIMIZATION NOT TESTED. Also, the final objective function
is not always the lowest one. An example is below. How do we interpret the
results in this case?


 iteration 0 OBJ= 10625.663135214874
 iteration 1 OBJ= 10601.188754983375
 iteration 2 OBJ= 10537.895114114934
 iteration 3 OBJ= 10471.674625518765
 iteration 4 OBJ= 10430.297437731866
 iteration 5 OBJ= 10461.973668565577
 iteration 6 OBJ= 10462.638834406265
 iteration 7 OBJ= 10423.464983371641
 iteration 8 OBJ= 10417.959956991735
 iteration 9 OBJ= 10417.594007447198
 iteration 10 OBJ= 10414.708468642830
 iteration 11 OBJ= 10427.810693855947
 iteration 12 OBJ= 10412.889081059604
 iteration 13 OBJ= 10411.980622268416
 iteration 14 OBJ= 10424.501127174915
 iteration 15 OBJ= 10416.332869468861
 iteration 16 OBJ= 10416.622580251338
 iteration 17 OBJ= 10412.401585537709
 iteration 18 OBJ= 10415.117257355550
 iteration 19 OBJ= 10415.302370961055
 iteration 20 OBJ= 10409.066188189252
 iteration 21 OBJ= 10413.780620468329
 iteration 22 OBJ= 10410.787496174480
 iteration 23 OBJ= 10410.633582415931
 iteration 24 OBJ= 10409.970257443048
 iteration 25 OBJ= 10409.702420124611
 iteration 26 OBJ= 10409.213115058612
 iteration 27 OBJ= 10409.690639357370
 iteration 28 OBJ= 10410.016047785200
 iteration 29 OBJ= 10408.157468814226
 iteration 30 OBJ= 10407.779614704938
 iteration 31 OBJ= 10410.164563157052
 iteration 32 OBJ= 10408.364552302961
 iteration 33 OBJ= 10407.431920727997
 iteration 34 OBJ= 10408.286189641487
 iteration 35 OBJ= 10407.907347050501
 iteration 36 OBJ= 10407.451608770069
 iteration 37 OBJ= 10407.189482360372
 iteration 38 OBJ= 10406.484357336147
 iteration 39 OBJ= 10409.167125968375
 iteration 40 OBJ= 10406.840873883246
 iteration 41 OBJ= 10407.679485561714
 iteration 42 OBJ= 10405.341101045238
 iteration 43 OBJ= 10404.704382334516
 iteration 44 OBJ= 10405.348023082915
 iteration 45 OBJ= 10405.347406984720
 iteration 46 OBJ= 10401.873473651774
 iteration 47 OBJ= 10404.036204419035
 iteration 48 OBJ= 10405.072916975221
 iteration 49 OBJ= 10402.976628923887
 Elapsed estimation time in seconds: 30420.73
 iteration 50 OBJ= 10403.285958168881








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Received on Mon Oct 26 2009 - 11:36:02 EDT

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