RE: [NMusers] $COV UNCONDITIONAL PRINT=E

[Mark Sale - Next Level Solutions]

Sam,    Many years ago Stuart scolded me for using the Unconditional option, saying that a model that didn't converge had no chance of a successful covariance step (I didn't ask why he put the option in if he didn't want people using it).  But, I have had put a couple of models that appeared to be "hung" into the development environment and found that they were not, in fact hung.  Almost invariably, the "hung" part is in the call to OBETA (I assume you're using FOCE?), OBETA is a minimization in itself, and while the main NONMEM minimization has a limit (MAXEVAL) OBETA doesn't seem to.  So, if the minimization (in OBETA) is difficult it will just keep running.  Options are to beleive those who claim covariance doesn't mean anything, or wait for the parallel version of NONMEM. Mark Mark Sale MD Next Level Solutions, LLC www.NextLevelSolns.com 919-846-9185 -------- Original Message -------- Subject: [NMusers] $COV UNCONDITIONAL PRINT=E From: "Sam Liao" <sl...@pharmaxresearch.com> Date: Mon, October 26, 2009 11:36 am To: <non...@optonline.net>, <nmusers@globomaxnm.com> 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? ======================= $SUBROUTINES ADVAN13 TOL=6                                                      $EST METHOD=BAYES NBURN=100 NSAMPLE=3000 SIGL=6 NOABORT FILE=RUN136.TXT   Best regards, Sam   From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Bauer, Robert Sent: Sunday, October 25, 2009 11:29 PM To: non...@optonline.net; nmusers@globomaxnm.com Subject: RE: [NMusers] method=ITS, OPTIMIZATION NOT TESTED (?!)   Pavel: 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: robert.ba...@iconplc.com Web: www.icondevsolutions.com         From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of non...@optonline.net Sent: Saturday, October 24, 2009 8:03 PM To: nmusers@globomaxnm.com 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?   THETAS THAT ARE SIGMA-LIKE:  MONITORING OF SEARCH:  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      #TERM:  OPTIMIZATION NOT TESTED Thanks, Pavel         ICON plc made the following annotations. ------------------------------------------------------------------------------ This e-mail transmission may contain confidential or legally privileged information that is intended only for the individual or entity named in the e-mail address. 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