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
********************************************************************************
Rounding (error=134) or obj. func. is infinite (error=136)
In $DES block I this expression
DSIZE = LOG(BSL*(EXP(-DEC*TIME) + EXP(GRO*TIME) - 1)+1)
I would use T rather than TIME
You may also try tol nsig=4 sign
Leonid
Quoted reply history
> On Apr 22, 2016, at 1:37 PM, Mai, Tu [MED] <tmai1
u> 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 p
rovided 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 wh
ich
> it is addressed and may contain information that is privileged and confide
ntial.
> If the reader of this e-mail message is not the intended recipient, you ar
e
> hereby notified that any dissemination, distribution or copying of this
> communication is prohibited. If you have received this e-mail in error, pl
ease
> notify the sender and destroy all copies of the transmittal.
>
> Thank you
> University of Chicago Medicine and Biological Sciences
> **************************************************************************
******
Dear NMUsers,
Our model keeps having the rounding error (error=134). I tried to fix it using
the following methods or their combinations, however, sometimes I then got the
message error=136 instead of error=134. 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
DECCOV=DECAGE*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
BETACOV=BETAAGE*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 MAX=9999 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
********************************************************************************
In $DES block I this expression
DSIZE = LOG(BSL*(EXP(-DEC*TIME) + EXP(GRO*TIME) - 1)+1)
I would use T rather than TIME
You may also try tol=12 nsig=4 sign=12
Leonid
Quoted reply history
> On Apr 22, 2016, at 1:37 PM, Mai, Tu [MED] <[email protected]>
> wrote:
>
> Dear NMUsers,
>
> Our model keeps having the rounding error (error=134). I tried to fix it
> using the following methods or their combinations, however, sometimes I then
> got the message error=136 instead of error=134. 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
>
> DECCOV=DECAGE*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
>
> BETACOV=BETAAGE*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 MAX=9999 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
> ********************************************************************************
Hi,
I would not be worried by rounding errors. Its more important to consider whether the parameter estimates are plausible and to evaluate the predictions using VPC. If the parameters are plausible and the VPC looks good then you can have some trust in your model.
I see you are doing a joint model of tumour size and hazard. Did you satisfy yourself that the tumour size model was good before trying to estimate the hazard parameters? I would always analyse this kind of data in a sequential fashion by fitting the tumour size first then fixing the tumour size parameters then fitting the hazard with the full data (tumour and event) (see Zhang et al. 2003). Once you have got some plausible hazard estimates you can then try doing a simultaneous fit. There is usually very little point in doing a simultaneous fit.
Best wishes,
Nick
Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis for population PK/PD data I: best-case performance. J Pharmacokinet Pharmacodyn. 2003;30(6):387-404.
Quoted reply history
On 23-Apr-16 01:37, Mai, Tu [MED] wrote:
> Dear NMUsers,
>
> Our model keeps having the rounding error (error=134). I tried to fix it using the following methods or their combinations, however, sometimes I then got the message error=136 instead of error=134. 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
>
> DECCOV=DECAGE*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
>
> BETACOV=BETAAGE*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 MAX=9999 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: [email protected]
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.
Dear Leonid and Nick,
Thank you very much for your inputs! We will work on our model with your
suggestions.
Thank you!
Tu
Sent from my iOS device
Quoted reply history
On Apr 22, 2016, at 9:14 PM, Leonid Gibiansky
<[email protected]<mailto:[email protected]>> wrote:
In $DES block I this expression
DSIZE = LOG(BSL*(EXP(-DEC*TIME) + EXP(GRO*TIME) - 1)+1)
I would use T rather than TIME
You may also try tol=12 nsig=4 sign=12
Leonid
On Apr 22, 2016, at 1:37 PM, Mai, Tu [MED]
<[email protected]<mailto:[email protected]>> wrote:
Dear NMUsers,
Our model keeps having the rounding error (error=134). I tried to fix it using
the following methods or their combinations, however, sometimes I then got the
message error=136 instead of error=134. 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
DECCOV=DECAGE*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
BETACOV=BETAAGE*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 MAX=9999 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
********************************************************************************
********************************************************************************
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
********************************************************************************