Re: Standard error for estimates
Dear Navin,
You probably have double definition code for VC and also problem
that CL and VC are not constants between patients because of ETA(3) and ETA(4)
$PK
F1=THETA(1)*EXP(ETA(1)+ETA(2))
K12=4;Abso constant
TVCL=THETA(2);Clearance
CL=TVCL*EXP(ETA(3))
TVVC=THETA(3);vol of dist of drug =====> delete
VC=TVVC*EXP(ETA(4)) =====> delete
K20=0.20;elim rate const of drug
VC=CL/K20 ====> OR rename VC1=CL/K20
S2=VC; OUTPUT IN ng/ml =====> scale S2 vs DOSE
sincerely
Kazimierz H. Kozlowski
navin goyal wrote:
> Hello everybody
>
> I am using Nonmem VI to model some Population Pk (10 subjects) data that I have.
>
> When I run this file.. I get the parameter estimates.
> However I fail to get any STANDARD ERROR of the estimates.
> I do sometimes get the R,S, T matrices when I change my initial estimates.
> Also the output file has following messages
>
> MINIMIZATION SUCCESSFUL
> MATRIX ALGORITHMICALLY SINGULAR
> AND ALGORITHMICALLY NON-POSITIVE-SEMIDEFINITE
> 0R MATRIX IS OUTPUT
> 0COVARIANCE STEP ABORTED
>
> My understanding (maybe I got it wrong) is that these R,S, T matrices are printed out when there are more than one solutions to the parameter estimates.
>
> is this right or does my control stream have some error within it.
>
> I checked the individual plots with the output data file. The individual and population predicted fits are quite decent..
>
> It also gives me the following error message in the dos window
>
> (WARNING 50) OPTION "UNCONDITIONAL" OF $COVARIANCE RECORD IS IGNORED WITH
> THIS RELEASE OF NONMEM.
>
> Could someone kindly help me with what is the error in my control stream or how would I be able to get the Std error for the estimates
>
> $PROBLEM PK
> $INPUT ID TIME AMT MDV DV EVID CMT
> $DATA file1.csv IGNORE=C
> $SUBROUTINE ADVAN6 TRANS1 TOL=5
> $MODEL
> COMP=(DEPOT,DEFDOSE);
> COMP=(CENTRAL);PLASMA
>
> $PK
>
> F1=THETA(1)*EXP(ETA(1)+ETA(2))
> K12=4;Abso constant
> TVCL=THETA(2);Clearance
> CL=TVCL*EXP(ETA(3))
> TVVC=THETA(3);vol of dist of drug
> VC=TVVC*EXP(ETA(4))
> K20=0.20;elim rate const of drug
> VC=CL/K20
> S2=VC; OUTPUT IN ng/ml
>
> $ERROR
> IPRED=F
> IRES=DV-IPRED
> DEL=0
> IF (IPRED.EQ.0) DEL=1
> IWRES=(1-DEL)*IRES/(IPRED+DEL)
> Y=F+F*ERR(1)
>
> $DES
> DADT(1)=-K12*A(1)
> DADT(2)=K12*A(1)-K20*A(2)
>
> $THETA
> (0.01,0.5,0.8); bioavailability
> (75 FIXED);CL
> (375 FIXED);VC
>
> $OMEGA
>
> $SIGMA
>
> $ESTIMATION METHOD=1 SIGDIGITS=2 MAXEVAL=9999 PRINT=5 POSTHOC
> $COVARIANCE UNCONDITIONAL
>
> $TABLE ID TIME AMT MDV DV EVID CMT IPRED IWRES IRES
> NOPRINT ONEHEADER FILE=sdtabsab335
>
> thanks a lot