When should a long run be aborted?
From: "Paul Hutson" prhutson@pharmacy.wisc.edu
Subject: [NMusers] When should a long run be aborted?
Date: Mon, November 22, 2004 11:27 am
Good Monday to you all (Tuesday to Nick and Steve):
I have a run underway on a 1 GHz TabletPC running NONMEM under Wings for
NONMEM. It has been underway since last Wednesday. I am not getting
every-10 reports of the parameters and gradients, but this has been the
case for me with WFN. Last Friday I did get a warning message:
PRED EXIT CODE 1
THETA= ...
OCCURS DURING SEARCH FOR ETA AT A NONZERO VALUE OF ETA
NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE
MAXIMUM NO. OF EVALUATIONS OF DIFFERENTIAL EQUATIONS, 100000, EXCEEDED.
(I have the GENFOR fix included in the installation.)
Haven't had an error message (or anything else for that matter) pop up over
the weekend. This is the most data-rich fit I've ever tried, with 8
observations of parent and metabolite for each of 33 subjects. Nothing in
terms of the PHARMA runs, I'm sure, but still I have no frame of reference
on how long I should wait. I would like advice regarding how long to let
this run continue before I assume that the thing is just chasing its
tail. I have another run on my 350 MHz desktop that is even more complex
(two metabolites), but I figured that if the 1 GHz wasn't ready, I
shouldn't expect my desktop dog to be done.
Control stream and data from 2 of the 33 subjects are appended. Thanks
for your advice. Paul
$PROBLEM E AND METABOLITE
$INPUT ID SUBJ TIME AMT II SS ADDL DV CMT EVID
$DATA ..\EXE3.CSV IGNORE=C
$SUBROUTINES ADVAN6 TRANS1 TOL=5
$MODEL NPAR=5 NCOMP=3 COMP=(DEPOT,DEFDOSE) COMP=(PARENT) COMP=(METAB)
$PK
KA=THETA(1)*EXP(ETA(1)); KABS
K=THETA(2)*EXP(ETA(2)); CL
V2=THETA(3)*EXP(ETA(3)); VC
FME=THETA(4); FME
KME=THETA(5)*EXP(ETA(4)); KME
S2=V2/1000; SCALING FOR PARENT
S3=V2/1000
CL=K/V2
AUC=AMT/CL
CLF=CL*FME
$DES
DADT(1)=-A(1)*KA; GUT
DADT(2)=A(1)*KA-A(2)*K; PARENT
DADT(3)=(A(2)*K*FME)-A(3)*KME; METABOLITE
$ERROR
FX=0
IF (F.EQ.0) FX=1
W=F+FX
IPRED=F
IRES=DV-IPRED
IWRES=IRES/W
Y = F*EXP(EPS(1))+EPS(2)
IF (CMT.EQ.3) THEN
Y= F*EXP(EPS(3))+EPS(4)
ENDIF
$THETA 1000 FIXED ; KA
$THETA (0.001,0.542,10) ; K
$THETA (0.001,1320,100000) ; V2
$THETA (0.001,0.829,1) ; FME
$THETA (0.01,3.11,100) ; KME
$OMEGA .189
$OMEGA .194
$OMEGA .459
$OMEGA .01
$SIGMA .619 .343 ; SIGP
$SIGMA .384 .128 ; SIGM
$ESTIMATION METHOD=1 SIGDIGITS=3 MAXEVAL=9999 POSTHOC PRINT=10
NOABORT MSFO=exem5.msf
;$COVR
$TABLE ID TIME KA K V2 FME KME CL AUC CLF NOPRINT FILE=exem5.fit
$SCAT ID VS (DV CMT CL)
$SCAT DV VS TIME BY CMT
$SCAT PRED VS TIME BY CMT
$SCAT RES VS TIME BY CMT
$SCAT IWRES VS DV BY CMT
$SCAT PRED VS DV BY CMT UNIT
CID Subject TIME AMT II SS ADDL DV CMT EVID
28 1313 0 25 24 2 2 . 1 1
28 1313 0 . . . . 0.424 2 0
28 1313 0 . . . . 0.102 3 0
28 1313 0.5 . . . . 26.8 2 0
28 1313 0.5 . . . . 4.29 3 0
28 1313 1 . . . . 10.9 2 0
28 1313 1 . . . . 2.89 3 0
28 1313 2 . . . . 4.45 2 0
28 1313 2 . . . . 1.12 3 0
28 1313 4 . . . . 1.24 2 0
28 1313 4 . . . . 0.443 3 0
28 1313 6 . . . . 0.749 2 0
28 1313 6 . . . . 0.257 3 0
28 1313 24 . . . . 0.433 2 0
28 1313 24 . . . . 0.151 3 0
28 1313 48 . . . . 0.372 2 0
28 1313 48 . . . . 0.124 3 0
10 1316 0 25 24 2 2 . 1 1
10 1316 0 . . . . 0.625 2 0
10 1316 0 . . . . 0.169 3 0
10 1316 0.5 . . . . 45 2 0
10 1316 0.5 . . . . 4.41 3 0
10 1316 1 . . . . 25.4 2 0
10 1316 1 . . . . 3.46 3 0
10 1316 2 . . . . 7.81 2 0
10 1316 2 . . . . 1.54 3 0
10 1316 4 . . . . 4.09 2 0
10 1316 4 . . . . 1.01 3 0
10 1316 6 . . . . 2.72 2 0
10 1316 6 . . . . 0.722 3 0
10 1316 24 . . . . 0.616 2 0
10 1316 24 . . . . 0.181 3 0
10 1316 48 . . . . 0.627 2 0
10 1316 48 . . . . 0.184 3 0
Paul Hutson, Pharm.D.
Associate Professor (CHS)
UW School of Pharmacy
777 Highland Avenue
Madison, WI 53705-2222
Tel: (608) 263-2496
FAX: (608) 265-5421
Pager: (608) 265-7000, #7856