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Re: Estimation of standard error

From: Huali Wu <hualiw>
Date: Thu, 3 Jul 2008 19:12:15 -0400

Dear Dr. Gibiansky:

You are correct about that. I have double checked my simulations with
WinNonlin and ADAPTII. And I found a mistake in the order of parameter
values.

Thank you very much for your correction!

Best regards,

Huali


----- Original Message -----
From: Leonid Gibiansky <LGibiansky
To: "Huali Wu" <hualiw
Cc: <nmusers
Sent: Thursday, July 03, 2008 5:40 PM
Subject: Re: [NMusers] Estimation of standard error


> 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 - 19:12:15 EDT

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