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= 2.00000000000000E+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=-2.9999

     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

(0,9,1000000) ;TVCL

(0,18,1000000) ;TVV1

(0,0.75,1000000) ;TVQ

(0,7,1000000) ;TVV2

(0,0.3,1000000) ;OMG_CL

(0,0.3,1000000) ;OMG_V1

(0,0.3,1000000) ;OMG_Q

(0,0.3,1000000) ;OMG_V2

(0,0.3,1000000) ;SGM_EXP

(0,0.3,1000000) ;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=9999 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

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