I think this is overkill to have 10 occasions, and this could be a
problem. Try to start first with 2 occasions (e.g, first 5 doses and the
rest). If this works it means that it is just a numerical problem.
Also, just to check, try
Y=LOG(F+0.0001)+EPS_EXP
to remove the possibility of F=0.
Thanks
Leonid
On 2/2/2018 4:17 AM, HUI, Ka Ho wrote:
Dear nmusers,
I have trouble figuring out the cause of the error I am encountering:
0INDIVIDUAL NO. 1 ID= 2.00E+00 (WITHIN-INDIVIDUAL)
DATA REC NO. 2
...
OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
F OR DERIVATIVE RETURNED BY PRED IS INFINITE (INF) OR NOT A NUMBER (NAN).
To my own experience, this error is usually due to some mistakes in the
coding, such as the div/0 error occurring at the dosing record. However,
for this time, after I eliminated a few other possible causes, it
appears that the error will occur whenever I remove the occasional
variability from the model (by fixing variability to ZERO), and this
makes no sense to me.
I have attached a minimal reproducible example at the bottom. Any help
is appreciated and thank you for your attention.
Best Regards,
Matthew
$SIZES DIMTMP=1000
$PROBLEM MODEL
$INPUT C ID DOSE_N AMT=DOSE_UM RATE=RATE_UM TIME CP_UM DV=CP_LN_UM
MDV EVID
$DATA DATAFILE_TEST.csv IGNORE=@
$SUBROUTINE ADVAN3 TRANS4
$PK
;SETTING LLOQ
IF (NEWIND.EQ.0) THEN
LN_LLOQ=-2.
ENDIF
;INTEROCCASION VARIABILITY
OCC1=0
IF (DOSE_N.EQ.1) OCC1=1
OCC2=0
IF (DOSE_N.EQ.2) OCC2=1
OCC3=0
IF (DOSE_N.EQ.3) OCC3=1
OCC4=0
IF (DOSE_N.EQ.4) OCC4=1
OCC5=0
IF (DOSE_N.EQ.5) OCC5=1
OCC6=0
IF (DOSE_N.EQ.6) OCC6=1
OCC7=0
IF (DOSE_N.EQ.7) OCC7=1
OCC8=0
IF (DOSE_N.EQ.8) OCC8=1
OCC9=0
IF (DOSE_N.EQ.9) OCC9=1
OCC10=0
IF (DOSE_N.EQ.10) OCC10=1
OCC11=0
IF (DOSE_N.EQ.11) OCC11=1
OCC12=0
IF (DOSE_N.EQ.12) OCC12=1
;THETA DEFINITION
TVCL=THETA(1)
TVV1=THETA(2)
TVQ=THETA(3)
TVV2=THETA(4)
OMG_CL=THETA(5)
OMG_V1=THETA(6)
OMG_Q=THETA(7)
OMG_V2=THETA(8)
SGM_EXP=THETA(9)
OMG_CL_OCC=THETA(10)
;ETA DEFINITION
ETA_CL=OMG_CL*ETA(1)
ETA_V1=OMG_V1*ETA(2)
ETA_Q=OMG_Q*ETA(3)
ETA_V2=OMG_V2*ETA(4)
ETA_CL_OCC=OMG_CL_OCC*(OCC1*ETA(5)+OCC2*ETA(6)+OCC3*ETA(7)+OCC4*ETA(8)+OCC5*ETA(9)+OCC6*ETA(10)+OCC7*ETA(11)+OCC8*ETA(12)+OCC9*ETA(13)+OCC10*ETA(14)+OCC11*ETA(15)+OCC12*ETA(16))
;EFFECT DEFINITION
;CLEARANCE
POP_CL=TVCL
CL=POP_CL*EXP(ETA_CL+ETA_CL_OCC)
;CENTRAL VOLUME
POP_V1=TVV1
V1=POP_V1*EXP(ETA_V1)
;INTERCOMPARTMENTAL CLEARANCE
POP_Q=TVQ
Q=POP_Q*EXP(ETA_Q)
;PERIPHERAL VOLUME
POP_V2=TVV2
V2=POP_V2*EXP(ETA_V2)
;REQUIRED CONSTANT
S1=V1
$THETA
(0,9,100) ;TVCL
(0,18,100) ;TVV1
(0,0.75,100) ;TVQ
(0,7,100) ;TVV2
(0,0.3,100) ;OMG_CL
(0,0.3,100) ;OMG_V1
(0,0.3,100) ;OMG_Q
(0,0.3,100) ;OMG_V2
(0,0.3,100) ;SGM_EXP
(0,0.3,100) ;OMG_CL_OCC ;Change to 0 FIX to remove occasional
variability
$ERROR
EPS_EXP=SGM_EXP*EPS(1)
Y=LOG(F)+EPS_EXP
$OMEGA BLOCK(1) 1 FIX ;ETA_CL
$OMEGA BLOCK(1) 1 FIX ;ETA_V1
$OMEGA BLOCK(1) 1 FIX ;ETA_Q
$OMEGA BLOCK(1) 1 FIX ;ETA_V2
$OMEGA BLOCK(1) 1 FIX ;ETA_CL_OCC1 ;Change to 0 FIX to remove
occasional variability
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC2
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC3
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC4
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC5
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC6
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC7
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC8
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC9
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC10
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC11
$OMEGA BLOCK(1) SAME ;ETA_CL_OCC12
$SIGMA
1 FIX ;EPS_EXP
$ESTIMATION MAXEVAL= PRINT=1 METHOD=1 INTERACTION NUMERICAL SLOW
LAPLACIAN NOABORT
$COVARIANCE PRINT=E
C,ID,DOSE_N,AMT=DOSE_UM,RATE=RATE_UM,TIME,CP_UM,DV=CP_LN_UM,MDV,EVID
.,2,1,32743.59651,5457.27,0,0,0,1,1
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