Re: NONLINEAR PK MODEL ERROR
Yuhong,
Usually this error points out to zero variance of the residual error. In this case, you have proportional error model. If prediction is zero (or close to zero) at some point, you may get it. I would try to estimate (rather than fix to zero) the additive part of the error model. One possible explanation is ALAG1 use: if the first observation is before ALAG1 time, you will get zero prediction (and this error)
Thanks
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 2/13/2012 4:20 PM, Yuhong Chen wrote:
> Dear nmusers,
> I have a compound with nonlinear CL. I tried to run the nonlinear model
> but got error message as following, could someone point out what could
> be the error in my control file or my data?
> Best regards,
> Yuhong
>
> 0PROGRAM TERMINATED BY OBJ
>
> ERROR IN CELS WITH INDIVIDUAL 1 ID= 1.00000000000000E+00
>
> SUM OF "SQUARED" WEIGHTED INDIVIDUAL RESIDUALS IS INFINITE
>
> MESSAGE ISSUED FROM ESTIMATION STEP
>
> AT INITIAL OBJ. FUNCTION EVALUATION
>
> My control file is
>
> $INPUT ID STUD STYP DOSE AMT EVID MDV TIME DV HEIG WT BMI AGE SEX RACE
>
> $DATA ../data/M_PK.NM.csv IGNORE=#
>
> $SUBROUTINE ADVAN6 TRANS1 TOL=3
> $MODEL NCOMP=3
> COMP=(DEPOT DEFDOSE)
> COMP=(CENT DEFOBS)
> COMP=(PERIPH)
>
> $PK
> ALAG1 = THETA(1)
> KA = THETA(2)
> V2 = THETA(3)
> Q = THETA(4)
> V3 = THETA(5)
> TVM = THETA(6)
> KM = THETA(7)
>
> ;####################################################################
> ; Define IIV parameters
>
> ;ZLAG = ETA(1)
> ;ZKA = ETA(2)
> ;ZV2 = ETA(3)
> ;ZQ3 = ETA(4)
> ;ZV3 = ETA(5)
> ZVM = ETA(1)
> ;ZKM = ETA(3)
>
> ;########################################################################
> ; NONMEM PK Parameter Definitions
>
> VM = TVM*EXP(ZVM)
> ;KM = TKM*EXP(ZKM)
> ;V2 = TV2*EXP(ZV2)
> ;Q = TQ3*EXP(ZQ3)
> ;V3 = TV3*EXP(ZV3)
> ;KA = TKA*EXP(ZKA)
> ;ALAG1 = TLAG*EXP(ZLAG)
>
> S2 = V2/1000
>
> ;###########################################################################
> $DES
> ; PK Model
> CP = A(2)/S2
> DADT(1) = - KA*A(1)
> DADT(2) = KA*A(1) - Q/V2*A(2) + Q/V3*A(3) - CP*VM/(KM+CP)
> DADT(3) = Q/V2*A(2) - Q/V3*A(3)
>
> ;###########################################################################
> $ERROR
> Y = F + F*EPS(1)+EPS(2)
> IPRE = F
>
> ;##########################################################################
> ; SECONDARY PARAMETERS
>
> ;##########################################################################
> $THETA
> (0,1) ; ALAG1 [hr]
> (0,4) ; KA [1/hr]
> (0,4) ; V2 [L]
> (0,0.1) ; Q3 [L/hr]
> (0,10) ; V3 [L]
> (0,100) ; VM [ng/mL/hr]
> (0,10) ; KM [ng/mL]
>
> $OMEGA
> ;0.5 ; ZLAG
> ;0 FIX ; ZKA
> ;0 FIX ; ZV2
> ;0 FIX ; ZQ3
> ;0 FIX ; ZV3
> 0.5 ; ZVM
> ;0.5 ; ZKM
>
> $SIGMA
> 0.02 ; Proportional
> 0 FIX ; Additive [ug/mL]
>
> $EST PRINT=20 MAXEVAL=9999 POSTHOC NOABORT METHOD=1 POSTHOC INTER
> MSF=MSFO.msf
> $COV MATRIX=S PRINT=E
>
> $TABLE ID TIME IPRE EVID MDV AMT DV ALAG1 VM KM V2 V3 Q KA ZVM
> STUD DOSE AGE WT BMI SEX RACE NOPRINT ONEHEADER FILE=nmout.tab