Re: [NMusers] Standard error for estimates

Dear Navin,
I suggest following codes, but you need carefuilly check it - I.m just
on holidays and writing from my head only.

$PROBLEM BIOAVAILABILITY MODEL
$INPUT ID TIME AMT MDV DV EVID CMT
$DATA file1.csv IGNORE=C
$SUBROUTINE ADVAN8 TRANS1 TOL=7
$MODEL
COMP=(DEPOT,DEFDOSE) ; ABSORPTION COMPARTMENT
COMP=(CENTRAL, DEFOBS) ; PLASMA COMPARTMENT

$PK

F1=THETA(1)*ETA(1)+ETA(2) ; HETEROSCEDASTIC LINEAR MODEL OF
INTERSUBJECTS VARIANCE - IF NOT GOOD PLEASE CORRECT
KA=4.0 ; IDENTICAL KA PARAMETER
FOR ALL PATIENTS IN [1/H]
K=0.20 ; IDENTICAL K -
ELIMINATION RATE CONSTANT IN [1/H] = BETA

TVCL=THETA(2) ; TYPICAL VALUE CL = 75 ML/MIN/KG
(FROM INTRAVENOUS STUDY ?)
CL=TVCL*EXP(ETA(3)) ; INDYVIDUAL CL ACCORDING TO ETA (3)
MODEL

TVVC=TVCL/K ; TYPICAL VALUE VOLUME OF
DISTRIBUTION IN [ML/KG] = 75 [ML/KG/H]/0.2 [1/H] = 375 [ML/KG]
VC=TVVC*EXP(ETA(4)) ; INDYVIDUAL VC ACCORDING TO ETA (4)
MODEL

S2=VC/1000 ; S2 IS SCALED ACCORDING TO
DOSE [MICROGRAMS/KG] AND 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)=-KA*A(1)
DADT(2)=KA*A(1)-CL/K*A(2)

$THETA
(0.01,0.5,0.8) ; TVF1 - THETA(1)
(75 FIXED) ; TVCL -THETA(1)

$OMEGA 0.02 0.1 0.1 0.05 ; ETA(1,2,3,4) - INTERSUBJECTS
VARIANCES

$SIGMA 0.07 ; ERR(1) - INTRASUBJECT VARIANCE

$ESTIMATION METHOD=1 INTERACTION LAPLACE SIGDIGITS=6 MAXEVAL=9999
PRINT=5 MSF=SDMSFSAB.335
$COVARIANCE UNCONDITIONAL MATRIX=S
$TABLE ID TIME AMT MDV DV EVID CMT IPRED IWRES IRES NOPRINT ONEHEADER
FILE=SDTABSAB.335
 
sincerely

          Kazimierz H. Kozlowski

navin goyal wrote:

> Dear Kazimierz,
> I guess I did not quite follow your suggestion Sir. Could you please
> elaborate briefly on it.
> I think what I intended o do was havea fixed theta value and apply
> some variability ETA(3) and ETA(4) to those parameter estimates.
> I apologise for not following you correctly. I failed to understand
> the last line modification that you suggested.
> S2=VC; OUTPUT IN ng/ml =====> scale S2 vs DOSE
>
> Thanks a lot for your help
>
> On 6/15/07, Kazimierz H. Kozlowski <k.kozlowski_at_czd.pl
> <mailto:k.kozlowski_at_czd.pl>> wrote:
>
> 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
>>

Received on Wed Jun 20 2007 - 16:24:49 EDT