From: Luu_Ken <*Ken.Luu*>

Date: Fri, 2 Feb 2018 19:28:51 +0000

Matthew,

I'm guessing this error occurs because you fix the $OMEGA BLOCK(1) for ETA_=

CL_OCC1 to 0. The way the model is parameterized, to get rid of the IOV, yo=

u only need to fix the OMG_CL_OCC to 0 in the $THETA block, and leave the $=

OMEGA BLOCK(1) for ETA_CL_OCC1 alone (fixed to 1). Agree with Leonid to red=

uce the IOVs to a more manageable number.

Ken

-----Original Message-----

From: owner-nmusers

Behalf Of Leonid Gibiansky

Sent: Friday, February 02, 2018 7:13 AM

To: HUI, Ka Ho <matthew.hui

Subject: Re: [NMusers] unidentified cause of "F OR DERIVATIVE RETURNED BY P=

RED IS INFINITE (INF) OR NOT A NUMBER (NAN)"

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 SLO=
*

W

*> LAPLACIAN NOABORT
*

*>
*

*> $COVARIANCE PRINT=E
*

*>
*

*> C,ID,DOSE_N,AMT=DOSE_UM,RATE=RATE_UM,TIME,CP_UM,DV=CP_LN_UM,MDV,EVI=
*

D

*>
*

*> .,2,1,32743.59651,5457.27,0,0,0,1,1
*

*>
*

*> .,2,1,0,0,6,730,6.593044534,0,0
*

*>
*

*> .,2,1,0,0,24,140,4.941642423,0,0
*

*>
*

*> .,2,1,0,0,48,20,2.995732274,0,0
*

*>
*

*> .,2,1,0,0,72,5.1,1.62924054,0,0
*

*>
*

*> .,2,1,0,0,96,1.7,0.530628251,0,0
*

*>
*

*> .,2,1,0,0,120,0.97,-0.030459207,0,0
*

*>
*

*> .,2,1,0,0,144,0.005,-3,0,0
*

*>
*

*> .,2,2,27286.33043,4547.72,0,0,0,1,4
*

*>
*

*> .,2,2,0,0,6,920,6.82437367,0,0
*

*>
*

*> .,2,2,0,0,24,46,3.828641396,0,0
*

*>
*

*> .,2,2,0,0,48,0.93,-0.072570693,0,0
*

*>
*

*> .,2,2,0,0,72,0.23,-1.46967597,0,0
*

*>
*

*> c,2,2,0,0,96,14,2.63905733,0,0
*

*>
*

*> .,2,2,0,0,120,0.06,-2.813410717,0,0
*

*>
*

*> .,2,3,27286.33043,4547.72,0,0,0,1,4
*

*>
*

*> .,2,3,0,0,6,910,6.8134446,0,0
*

*>
*

*> .,2,3,0,0,24,16,2.772588722,0,0
*

*>
*

*> .,2,3,0,0,48,0.28,-1.272965676,0,0
*

*>
*

*> .,2,3,0,0,72,0.09,-2.407945609,0,0
*

*>
*

*> .,2,3,0,0,96,0,0,1,2
*

*>
*

*> .,2,4,27286.33043,4547.72,0,0,0,1,4
*

*>
*

*> .,2,4,0,0,6,820,6.70930434,0,0
*

*>
*

*> .,2,4,0,0,24,9.7,2.272125886,0,0
*

*>
*

*> .,2,4,0,0,48,1.7,0.530628251,0,0
*

*>
*

*> .,2,4,0,0,72,0.14,-1.966112856,0,0
*

*>
*

*> .,2,4,0,0,96,0.005,-3,0,0
*

*>
*

*> .,2,5,27286.33043,4547.72,0,0,0,1,4
*

*>
*

*> .,2,5,0,0,6,900,6.802394763,0,0
*

*>
*

*> .,2,5,0,0,24,30,3.401197382,0,0
*

*>
*

*> .,2,5,0,0,48,1.9,0.641853886,0,0
*

*>
*

*> .,2,5,0,0,72,0.32,-1.139434283,0,0
*

*>
*

*> .,2,5,0,0,96,0.19,-1.660731207,0,0
*

*>
*

*> .,2,5,0,0,120,0.07,-2.659260037,0,0
*

*>
*

*> .,2,6,27286.33043,4547.72,0,0,0,1,4
*

*>
*

*> .,2,6,0,0,6,710,6.56526497,0,0
*

*>
*

*> .,2,6,0,0,24,6.3,1.840549633,0,0
*

*>
*

*> .,2,6,0,0,48,0.27,-1.30933332,0,0
*

*>
*

*> .,2,6,0,0,72,0.08,-2.525728644,0,0
*

*>
*

*> .,3,1,48235.19056,8039.2,0,0,0,1,1
*

*>
*

*> .,3,1,0,0,6,750,6.620073207,0,0
*

*>
*

*> .,3,1,0,0,24,29.5,3.384390263,0,0
*

*>
*

*> .,3,1,0,0,48,3.5,1.252762968,0,0
*

*>
*

*> .,3,1,0,0,72,0.77,-0.261364764,0,0
*

*>
*

*> .,3,1,0,0,96,0.47,-0.755022584,0,0
*

*>
*

*> .,3,1,0,0,120,0.005,-3,0,0
*

*>
*

*> .,3,2,30146.9941,5024.5,0,0,0,1,4
*

*>
*

*> .,3,2,0,0,24,30,3.401197382,0,0
*

*>
*

*> .,3,2,0,0,48,1.7,0.530628251,0,0
*

*>
*

*> .,3,2,0,0,72,0.71,-0.342490309,0,0
*

*>
*

*> .,3,2,0,0,96,0.35,-1.049822124,0,0
*

*>
*

*> .,3,2,0,0,120,0.29,-1.237874356,0,0
*

*>
*

*> .,3,2,0,0,144,0.005,-3,0,0
*

*>
*

*> .,3,3,24117.59528,4019.6,0,0,0,1,4
*

*>
*

*> .,3,3,0,0,6,660,6.492239835,0,0
*

*>
*

*> .,3,3,0,0,24,18.5,2.917770732,0,0
*

*>
*

*> .,3,3,0,0,48,0.95,-0.051293294,0,0
*

*>
*

*> .,3,3,0,0,72,0.41,-0.891598119,0,0
*

*>
*

*> .,3,3,0,0,96,0.19,-1.660731207,0,0
*

*>
*

*> .,3,3,0,0,120,0.13,-2.040220829,0,0
*

*>
*

*> .,3,3,0,0,144,0.005,-3,0,0
*

*>
*

*> .,3,4,24117.59528,4019.6,0,0,0,1,4
*

*>
*

*> .,3,4,0,0,6,620,6.429719478,0,0
*

*>
*

*> .,3,4,0,0,24,8.3,2.116255515,0,0
*

*>
*

*> .,3,4,0,0,48,1.7,0.530628251,0,0
*

*>
*

*> .,3,4,0,0,72,0.17,-1.771956842,0,0
*

*>
*

*> .,3,4,0,0,96,0.09,-2.407945609,0,0
*

*>
*

*> .,3,5,27132.29469,4522.05,0,0,0,1,4
*

*>
*

*> .,3,5,0,0,6,870,6.768493212,0,0
*

*>
*

*> .,3,5,0,0,24,22.5,3.113515309,0,0
*

*>
*

*> .,3,5,0,0,48,0.94,-0.061875404,0,0
*

*>
*

*> .,3,5,0,0,72,0.43,-0.84397007,0,0
*

*>
*

*> .,3,5,0,0,96,0.21,-1.560647748,0,0
*

*>
*

*> .,3,5,0,0,120,0.14,-1.966112856,0,0
*

*>
*

*> .,3,5,0,0,144,0.005,-3,0,0
*

*>
*

*> .,3,6,27132.29469,4522.05,0,0,0,1,4
*

*>
*

*> .,3,6,0,0,6,660,6.492239835,0,0
*

*>
*

*> .,3,6,0,0,24,7.2,1.974081026,0,0
*

*>
*

*> .,3,6,0,0,48,0.6,-0.510825624,0,0
*

*>
*

*> .,3,6,0,0,72,0.21,-1.560647748,0,0
*

*>
*

*> .,3,6,0,0,96,0.1,-2.302585093,0,0
*

*>
*

*> .,3,6,0,0,120,0.005,-3,0,0
*

*>
*

*> .,3,7,27132.29469,4522.05,0,0,0,1,4
*

*>
*

*> .,3,7,0,0,6,720,6.579251212,0,0
*

*>
*

*> .,3,7,0,0,24,14.4,2.667228207,0,0
*

*>
*

*> .,3,7,0,0,48,0.51,-0.673344553,0,0
*

*>
*

*> .,3,7,0,0,72,0.17,-1.771956842,0,0
*

*>
*

*> .,3,7,0,0,96,0.09,-2.407945609,0,0
*

*>
*

*> .,3,8,27132.29469,4522.05,0,0,0,1,4
*

*>
*

*> .,3,8,0,0,6,830,6.721425701,0,0
*

*>
*

*> .,3,8,0,0,24,12.5,2.525728644,0,0
*

*>
*

*> .,3,8,0,0,48,0.85,-0.162518929,0,0
*

*>
*

*> .,3,8,0,0,72,0.44,-0.820980552,0,0
*

*>
*

*> .,3,8,0,0,96,0.29,-1.237874356,0,0
*

*>
*

*> .,3,8,0,0,120,0.2,-1.609437912,0,0
*

*>
*

*> .,3,8,0,0,144,0.005,-3,0,0
*

*>
*

*> .,3,9,27132.29469,4522.05,0,0,0,1,4
*

*>
*

*> .,3,9,0,0,6,670,6.507277712,0,0
*

*>
*

*> .,3,9,0,0,24,8.5,2.140066163,0,0
*

*>
*

*> .,3,9,0,0,48,0.77,-0.261364764,0,0
*

*>
*

*> .,3,9,0,0,72,0.34,-1.078809661,0,0
*

*>
*

*> .,3,9,0,0,96,0.18,-1.714798428,0,0
*

*>
*

*> .,3,9,0,0,120,0.05,-2.995732274,0,0
*

*>
*

*> .,3,10,27132.29469,4522.05,0,0,0,1,4
*

*>
*

*> .,3,10,0,0,6,1080,6.98471632,0,0
*

*>
*

*> .,3,10,0,0,24,56,4.025351691,0,0
*

*>
*

*> .,3,10,0,0,48,5.1,1.62924054,0,0
*

*>
*

*> .,3,10,0,0,72,1.5,0.405465108,0,0
*

*>
*

*> .,3,10,0,0,96,0.64,-0.446287103,0,0
*

*>
*

*> .,3,10,0,0,120,0.54,-0.616186139,0,0
*

*>
*

*> .,3,10,0,0,144,0.31,-1.171182982,0,0
*

*>
*

*> .,3,10,0,0,168,0.23,-1.46967597,0,0
*

*>
*

*> .,3,10,0,0,192,0.12,-2.120263536,0,0
*

*>
*

*> .,3,10,0,0,216,0.06,-2.813410717,0,0
*

*>
*

*> .,3,11,24117.59528,4019.6,0,0,0,1,4
*

*>
*

*> .,3,11,0,0,6,870,6.768493212,0,0
*

*>
*

*> .,3,11,0,0,24,19.2,2.954910279,0,0
*

*>
*

*> .,3,11,0,0,48,0.87,-0.139262067,0,0
*

*>
*

*> .,3,11,0,0,72,0.4,-0.916290732,0,0
*

*>
*

*> .,3,11,0,0,96,0.2,-1.609437912,0,0
*

*>
*

*> .,3,11,0,0,120,0.12,-2.120263536,0,0
*

*>
*

*> .,3,11,0,0,144,0.005,-3,0,0
*

*>
*

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Received on Fri Feb 02 2018 - 14:28:51 EST

Date: Fri, 2 Feb 2018 19:28:51 +0000

Matthew,

I'm guessing this error occurs because you fix the $OMEGA BLOCK(1) for ETA_=

CL_OCC1 to 0. The way the model is parameterized, to get rid of the IOV, yo=

u only need to fix the OMG_CL_OCC to 0 in the $THETA block, and leave the $=

OMEGA BLOCK(1) for ETA_CL_OCC1 alone (fixed to 1). Agree with Leonid to red=

uce the IOVs to a more manageable number.

Ken

-----Original Message-----

From: owner-nmusers

Behalf Of Leonid Gibiansky

Sent: Friday, February 02, 2018 7:13 AM

To: HUI, Ka Ho <matthew.hui

Subject: Re: [NMusers] unidentified cause of "F OR DERIVATIVE RETURNED BY P=

RED IS INFINITE (INF) OR NOT A NUMBER (NAN)"

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:

W

D

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Received on Fri Feb 02 2018 - 14:28:51 EST