Re: Rounding (error=134) or obj. func. is infinite (error=136)

On 23-Apr-16 01:37, Mai, Tu [MED] wrote: > > Dear NMUsers, > > Our model keeps having the rounding error (error4). I tried to fix > it using the following methods or their combinations, however, > sometimes I then got the message error6 instead of error4. But > minimization still unsuccessful. Can you please help pointing out how > I can solve this problem? I really appreciate it! > > Thank you > > 1) Use the estimates for THETA that are ~10% deviated from the > estimates provided after scm run. > > 2) Set TOL=9, NSIG=2, SIGL=6 > > I attached here the code: > > $PROBLEM IRM code > > $INPUT ID TIME EX DV DVID ECOG AGE HT WT RACE SITE DIAG=DROP HEM > > ALK ALB LAC TES STUDY DRUG PRIORDOC > > $DATA survival.csv > > $SUBROUTINE ADVAN13 TOL=9 > > $MODEL NCOMP=1 COMP(HAZ) > > $PK > > ;;; DECECOG-DEFINITION START > > IF(ECOG.EQ.1) DECECOG = 1 ; Most common > > IF(ECOG.EQ.0) DECECOG = ( 1 + THETA(27)) > > IF(ECOG.EQ.2) DECECOG = ( 1 + THETA(28)) > > ;;; DECECOG-DEFINITION END > > ;;; GROPRIORDOC-DEFINITION START > > IF(PRIORDOC.EQ.0) GROPRIORDOC = 1 ; Most common > > IF(PRIORDOC.EQ.1) GROPRIORDOC = ( 1 + THETA(26)) > > ;;; GROPRIORDOC-DEFINITION END > > ;;; GROECOG-DEFINITION START > > IF(ECOG.EQ.1) GROECOG = 1 ; Most common > > IF(ECOG.EQ.0) GROECOG = ( 1 + THETA(24)) > > IF(ECOG.EQ.2) GROECOG = ( 1 + THETA(25)) > > ;;; GROECOG-DEFINITION END > > ;;; GROALK-DEFINITION START > > IF(ALK.EQ.-99) THEN > > GROALK = 1 > > ELSE > > GROALK = ( 1 + THETA(23)*(ALK - 94.00)) > > ENDIF > > ;;; GROALK-DEFINITION END > > ;;; GRO-RELATION START > > GROCOV=GROALK*GROECOG*GROPRIORDOC > > ;;; GRO-RELATION END > > ;;; DECDRUG-DEFINITION START > > IF(DRUG.EQ.3) DECDRUG = 1 ; Most common > > IF(DRUG.EQ.2) DECDRUG = ( 1 + THETA(21)) > > IF(DRUG.EQ.1) DECDRUG = ( 1 + THETA(22)) > > ;;; DECDRUG-DEFINITION END > > ;;; DECAGE-DEFINITION START > > DECAGE = ( 1 + THETA(20)*(AGE - 64.00)) > > ;;; DECAGE-DEFINITION END > > ;;; DEC-RELATION START > > DECCOVCAGE*DECDRUG*DECECOG > > ;;; DEC-RELATION END > > ;;; BSLHEM-DEFINITION START > > IF(HEM.LE.124.00) BSLHEM = ( 1 + THETA(18)*(HEM - 124.00)) > > IF(HEM.GT.124.00) BSLHEM = ( 1 + THETA(19)*(HEM - 124.00)) > > IF(HEM.EQ.-99) BSLHEM = 1 > > ;;; BSLHEM-DEFINITION END > > ;;; BSLECOG-DEFINITION START > > IF(ECOG.EQ.1) BSLECOG = 1 ; Most common > > IF(ECOG.EQ.0) BSLECOG = ( 1 + THETA(16)) > > IF(ECOG.EQ.2) BSLECOG = ( 1 + THETA(17)) > > ;;; BSLECOG-DEFINITION END > > ;;; BSLALK-DEFINITION START > > IF(ALK.EQ.-99) THEN > > BSLALK = 1 > > ELSE > > BSLALK = ( 1 + THETA(15)*(ALK - 94.00)) > > ENDIF > > ;;; BSLALK-DEFINITION END > > ;;; BSL-RELATION START > > BSLCOV=BSLALK*BSLECOG*BSLHEM > > ;;; BSL-RELATION END > > ;;; BSHZPRIORDOC-DEFINITION START > > IF(PRIORDOC.EQ.0) BSHZPRIORDOC = 1 ; Most common > > IF(PRIORDOC.EQ.1) BSHZPRIORDOC = ( 1 + THETA(14)) > > ;;; BSHZPRIORDOC-DEFINITION END > > ;;; BSHZALK-DEFINITION START > > IF(ALK.EQ.-99) THEN > > BSHZALK = 1 > > ELSE > > BSHZALK = ( 1 + THETA(13)*(ALK - 94.00)) > > ENDIF > > ;;; BSHZALK-DEFINITION END > > ;;; BSHZ-RELATION START > > BSHZCOV=BSHZALK*BSHZPRIORDOC > > ;;; BSHZ-RELATION END > > ;;; BETAHEM-DEFINITION START > > IF(HEM.EQ.-99) THEN > > BETAHEM = 1 > > ELSE > > BETAHEM = ( 1 + THETA(12)*(HEM - 124.00)) > > ENDIF > > ;;; BETAHEM-DEFINITION END > > ;;; BETAECOG-DEFINITION START > > IF(ECOG.EQ.1) BETAECOG = 1 ; Most common > > IF(ECOG.EQ.0) BETAECOG = ( 1 + THETA(10)) > > IF(ECOG.EQ.2) BETAECOG = ( 1 + THETA(11)) > > ;;; BETAECOG-DEFINITION END > > ;;; BETADRUG-DEFINITION START > > IF(DRUG.EQ.3) BETADRUG = 1 ; Most common > > IF(DRUG.EQ.2) BETADRUG = ( 1 + THETA(8)) > > IF(DRUG.EQ.1) BETADRUG = ( 1 + THETA(9)) > > ;;; BETADRUG-DEFINITION END > > ;;; BETAAGE-DEFINITION START > > BETAAGE = ( 1 + THETA(7)*(AGE - 64.00)) > > ;;; BETAAGE-DEFINITION END > > ;;; BETA-RELATION START > > BETACOVTAAGE*BETADRUG*BETAECOG*BETAHEM > > ;;; BETA-RELATION END > > IF (NEWIND.LE.1) THEN > > SRVZ=1 ; Survivor function at TIME=0 > > ENDIF > > ;-----------BASELINE PSA-------------- > > TVBSL = THETA(1) > > TVBSL = BSLCOV*TVBSL > > BSL = TVBSL*EXP(ETA(1)) > > ;-----------PSA PARAMETERS-------------- > > TVGRO = THETA(2) > > TVGRO = GROCOV*TVGRO > > TVDEC = THETA(3) > > TVDEC = DECCOV*TVDEC > > GRO = TVGRO*EXP(ETA(2)) > > DEC = TVDEC*EXP(ETA(3)) > > ;-----------SURVIVAl MODEL PARAMETERS-------------- > > TVBSHZ = THETA(5) ; Baseline Hazard > > TVBSHZ = BSHZCOV*TVBSHZ > > BSHZ = TVBSHZ > > TVBETA = THETA(6) ; Parameter relating dropout hazard to PSA estimate > > TVBETA = BETACOV*TVBETA > > BETA = TVBETA > > $DES > > DSIZE = LOG(BSL*(EXP(-DEC*TIME) + EXP(GRO*TIME) - 1)+1) > > TEMP = BETA*DSIZE > > DADT(1) = BSHZ*EXP(TEMP) > > $ERROR > > IF (DVID.EQ.1) THEN > > F_FLAG=0 ; If continuous type data > > SIZE = LOG(BSL*(EXP(-DEC*TIME) + EXP(GRO*TIME) - 1)+1) > > IPRED = SIZE > > ADD = THETA(4) > > SDSIZE = SQRT(ADD*ADD) > > Y = SIZE + SDSIZE*EPS(1) > > W = Y > > IRES = DV-IPRED > > IWRES = IRES/(W) > > ENDIF > > ;-----------HAZARD PREDICTION-------------- > > CMHZ = A(1) > > SRVT = EXP(-CMHZ) > > IF (DVID.EQ.2.AND.DV.EQ.0) THEN > > F_FLAG=1 > > Y = SRVT > > ENDIF > > IF (DVID.EQ.2.AND.DV.EQ.1) THEN > > F_FLAG=1 > > Y = SRVZ-SRVT > > ENDIF > > $THETA (50,85,150) ; POP_BSL > > (0,0.0004,0.1) ; POP_GRO > > (0,0.02,0.1) ; POP_DEC > > (0,0.3,0.35) ; ADD_SD > > (0,0.0009,0.0014) ; BSHZ > > (0.1,0.3,0.7) ; BETA > > $THETA (-0.038,-0.003,0.016) ; BETAAGE1 > > $THETA (-1,0.3,5) ; BETADRUG1 > > (-1,0.1,5) ; BETADRUG2 > > $THETA (-1,-0.2,5) ; BETAECOG1 > > (-1,0.3,5) ; BETAECOG2 > > $THETA (-0.023,-0.01,0.016) ; BETAHEM1 > > $THETA (0,0.001,0.010) ; BSHZALK1 > > $THETA (-1,-0.4,5) ; BSHZPRIORDOC1 > > $THETA (0,0.002,0.010) ; BSLALK1 > > $THETA (-1,-0.3,5) ; BSLECOG1 > > (-1,0.2,5) ; BSLECOG2 > > $THETA (-1000000,-0.05,0.016) ; BSLHEM1 > > (-0.023,-0.0002,100) ; BSLHEM2 > > $THETA (-0.038,-0.0009,0.016) ; DECAGE1 > > $THETA (-1,-0.6,5) ; DECDRUG1 > > (-1,-0.8,5) ; DECDRUG2 > > $THETA (0,98E-006,0.010) ; GROALK1 > > $THETA (-1,-0.02,5) ; GROECOG1 > > (-1,0.5,5) ; GROECOG2 > > $THETA (-1,5,7) ; GROPRIORDOC1 > > $THETA (-1,0.0004,5) ; DECECOG1 > > (-1,-0.2,5) ; DECECOG2 > > $OMEGA 2.5 ; PPV_BSL > > 2 ; PPV_GRO > > 1.5 ; PPV_DEC > > ;------------------------- > > $SIGMA 1. FIX > > ;------------------------- > > $ESTIMATION METHOD=COND INTER NUMERICAL LAPLACE SLOW MAX99 NSIG=2 > > SIGL=6 NOABORT PRINT=5 > > $COVARIANCE > > $TABLE ID TIME IPRED BSL GRO DEC STUDY DRUG WRES CWRES ETA1 ETA2 > > ETA3 ONEHEADER NOPRINT > > FILE=C:\Users\fulldata.tab > > $TABLE ID TIME PRED RES WRES ONEHEADER NOPRINT > > FILE=C:\Users\original.tab > > ******************************************************************************** > This e-mail is intended only for the use of the individual or entity > to which > it is addressed and may contain information that is privileged and > confidential. > If the reader of this e-mail message is not the intended recipient, > you are > hereby notified that any dissemination, distribution or copying of this > communication is prohibited. If you have received this e-mail in > error, please > notify the sender and destroy all copies of the transmittal. > > Thank you > University of Chicago Medicine and Biological Sciences > ******************************************************************************** -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand office:+64(9)923-6730 mobile:NZ+64(21)46 23 53 FR+33(6)62 32 46 72 email: n.holford_at_auckland.ac.nz http://holford.fmhs.auckland.ac.nz/ "Declarative languages are a form of dementia -- they have no memory of events" Holford SD, Allegaert K, Anderson BJ, Kukanich B, Sousa AB, Steinman A, Pypendop, B., Mehvar, R., Giorgi, M., Holford,N.H.G. Parent-metabolite pharmacokinetic models - tests of assumptions and predictions. Journal of Pharmacology & Clinical Toxicology. 2014;2(2):1023-34. Holford N. Clinical pharmacology = disease progression + drug action. Br J Clin Pharmacol. 2015;79(1):18-27.