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Re: Estimation of standard error

From: Leonid Gibiansky <LGibiansky>
Date: Thu, 03 Jul 2008 17:40:05 -0400

Huali
Even if it gives a good fit, S2=V1 is still an error. You may try to
assume that V2=V1, and then S2=V2=V1, it is fine, but in the current
form, equations are incorrect
Thanks
Leonid

--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566




Huali Wu wrote:
> Dear Dr. Gibiansky:
>
> Thank you very much for your suggestions.
>
> MATRIX=S did work. But S2 = V2 did not. Also, S2 = V1 is not an error, I
> validated that by comparing the simulation results from WinNonlin and
> NONMEM without adding any error. I don't understand why but if S2 = V2
> will only give discrepant result.
>
> For the error model, I have tried separate errors for each CMT. But it
> did not give good fit of released drug.
>
> Thanks again,
>
> Best regards,
>
> Huali
>
> ----- Original Message ----- From: "Leonid Gibiansky"
> <LGibiansky
> To: "Huali Wu" <hualiw
> Cc: <nmusers
> Sent: Thursday, July 03, 2008 3:00 PM
> Subject: Re: [NMusers] Estimation of standard error
>
>
>> Huali and Nick,
>> Failure of $COV step sometimes tells about errors in the code. In this
>> case, I think the problem is in
>> S2 = V1
>>
>> should it be
>> S2 = V2 ?
>>
>> Also,
>> > Y1=F+F*EPS(1)
>> > Y2=F+F*EPS(1)
>> > Y=R1*Y1+R2*Y2
>>
>> results in
>> Y =F+F*EPS(1)
>> for both MCT=1 and CMT=2
>> so R1 / R2 /Y1 /Y2 part can be omitted. Or you can use separate errors
>> for each CMT:
>>
>> > Y1=F+F*EPS(1)
>> > Y2=F+F*EPS(2)
>> > Y=R1*Y1+R2*Y2
>> --
>>
>> S2 = V2 should help to get SE. If not, try MATRIX=S on $COV line.
>> Leonid
>>
>> --------------------------------------
>> Leonid Gibiansky, Ph.D.
>> President, QuantPharm LLC
>> web: www.quantpharm.com
>> e-mail: LGibiansky at quantpharm.com
>> tel: (301) 767 5566
>>
>>
>>
>>
>> Huali Wu wrote:
>>> Dear NMusers:
>>> I am trying to fit a data set with concentrations of encapsulated
>>> drug and released drug. These concentrations were measured after an
>>> hour infusion of encapsulated drug. The problem is that I cannot get
>>> standard error estimated from simultaneous fitting of all the data.
>>> And I got an error message as below:
>>> MINIMIZATION SUCCESSFUL
>>> HOWEVER, PROBLEMS OCCURRED WITH THE MINIMIZATION.
>>> REGARD THE RESULTS OF THE ESTIMATION STEP CAREFULLY, AND ACCEPT THEM
>>> ONLY
>>> AFTER CHECKING THAT THE COVARIANCE STEP PRODUCES REASONABLE OUTPUT.
>>> NO. OF FUNCTION EVALUATIONS USED: 968
>>> NO. OF SIG. DIGITS IN FINAL EST.: 3.2
>>> R MATRIX ALGORITHMICALLY NON-POSITIVE-SEMIDEFINITE
>>> BUT NONSINGULAR
>>> R MATRIX IS OUTPUT
>>> COVARIANCE STEP ABORTED
>>> But if I fit the encapsulated drug first and then fit data of both
>>> encapsulated drug and released drug by fixing the typical values of
>>> parameters associated with encapsulated drug compartment, I can get
>>> an estimation of standard errors. And GOF plots look good.
>>> So my question is can I use this stepwise strategy to build up my
>>> base model? If not, what can I do to get standard error estimated in
>>> simultaneous fitting?
>>> Any comment or suggestion will be highly appreciated.
>>> Below is my code:
>>> $SUBROUTINES ADVAN9 TRANS1 TOL=3
>>> $MODEL NPAR=8, NCOMP=3, COMP=(CENTRAL,DEFOBS),
>>> COMP=(PERIPH1), COMP=(PERIPH2)
>>> $PK
>>> V1 = THETA(1)*EXP(ETA(1))
>>> V2 = THETA(2)*EXP(ETA(2))
>>> V3 = THETA(3)
>>> VM = THETA(4)
>>> KM = THETA(5)
>>> Q2 = THETA(6)*EXP(ETA(3))
>>> Q3 = THETA(7)
>>> Q4 = THETA(8) S1 = V1
>>> S2 = V1
>>> $ERROR
>>> R1=0
>>> IF (CMT.EQ.1) R1=1
>>> R2=0
>>> IF (CMT.EQ.2) R2=1
>>> Y1=F+F*EPS(1)
>>> Y2=F+F*EPS(1)
>>> Y=R1*Y1+R2*Y2
>>> IPRED=F
>>> IRES=DV-IPRED
>>> $DES
>>> C1 = A(1)/V1
>>> DADT(1) = - C1*VM/(KM+C1)-Q2*A(1)/V1
>>> DADT(2) = C1*VM/(KM+C1)+Q2*A(1)/V1 + Q4*A(3)/V3-
>>> Q3*A(2)/V2-Q4*A(2)/V2
>>> DADT(3) = Q4*A(2)/V2-Q4*A(3)/V3 $THETA (5.27 FIX)
>>> (0, 0.5) (0, 3.38) (0.329 FIX) (4.38 FIX) (0.136 FIX) (0, 0.0626) (0,
>>> 0.0461)
>>> $OMEGA (0.01) (0.01) (0.01)
>>> $SIGMA (.1)
>>>
>>> $EST MAXEVAL=9999 PRINT=5
>>> $COV
>>> $TABLE ID TIME DV AMT RATE CMT NOPRINT FILE=ENCAP4 ONEHEADER
>>> $SCAT (RES WRES) VS TIME BY ID
>>> Best regards,
>>> Huali
>>>
>>
>
>
Received on Thu Jul 03 2008 - 17:40:05 EDT

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