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Re: OMEGA-Block

From: Hauke Rühs <hauke_ruehs>
Date: Tue, 04 Aug 2009 11:24:25 +0200



Dear Samer,
I parameterized the model by CL, Q , V1 and V2 and by CL,Q, V1 and Vss
respectively. Correlation was not included at this time. The latter model
lead to a lower OFV (~5), which is why I choosed to go on with this
paramerization. Both models show correlation between the volumes V1 and V2
or V1 and VSS respectively in the scatter plot matrix of random effect,
when no correlation is included into the model. So is it better to go with
parameterization CL, Q, V1 and V2, even though I have correlation in both
cases?

Hauke


Am 03.08.2009, 18:42 Uhr, schrieb Samer Mouksassi
<smouksassi

> What do you mean by much better ?
> OFV ? BSV % etc..
> Can you please in clude a brief comparison on both cases
>
> Samer
>
>
> -----Original Message-----
> From: owner-nmusers
> On Behalf Of Hauke Rhs
> Sent: 2009-08-03 12:06
> To: nmusers
> Subject: Re: [NMusers] OMEGA-Block
>
>
> Dear NMusers,
>
> thank you for your responses. I parameterized the model by VSS, because
> the estimation of the parameter became much better, in terms of
> varability, compared to parameterization by V1 and V2.
> This is the excerpt from my control stream and output file:
>
>
> $PK
> CL = THETA(1) * EXP(ETA(1))
> Q = THETA(2) * EXP(ETA(2))
> V1 = THETA(3)* EXP(ETA(3))
> VSS = THETA(4) * EXP(ETA(4))
> V2=VSS-V1
>
> $OMEGA
> 0.1 ; OMCL
> 0.5 ;OMQ
> $OMEGA BLOCK(2)
> 0.05 ;OMV1
> 0.01 0.05 ;OMVSS
>
>
> OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS ********
>
>
> ETA1 ETA2 ETA3 ETA4
>
> ETA1
> + 4.08E-02
>
> ETA2
> + 0.00E+00 4.56E-01
>
> ETA3
> + 0.00E+00 0.00E+00 2.62E-01
>
> ETA4
> + 0.00E+00 0.00E+00 -4.34E-02 7.20E-03
>
>
> Best regards
>
> Hauke
>
>
>
>
> Am 03.08.2009, 16:37 Uhr, schrieb Grevel, Joachim
> <Joachim.Grevel
>
>> Hello Hauke,
>>
>> as always for these specific questions you need to provide us with the
>> relevant portions of your control stream and of your output.
>>
>> Thanks for participating,
>>
>> Joachim
>> _________________________________
>> AstraZeneca R&D Charnwood
>> Clin. Pharmacology and DMPK
>> Bakewell Road
>> Loughborough, LE11 5RH
>> Tel: +44 1509 644035
>> joachim.grevel
>>
>>
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>> -----Original Message-----
>> From: owner-nmusers
>> [mailto:owner-nmusers
>> Sent: 03 August 2009 15:07
>> To: nmusers
>> Subject: [NMusers] OMEGA-Block
>>
>>
>>
>> Dear NMusers,
>>
>> modelling a 2-compartmet model parameterized by CL, V1, VSS and Q, I got
>> to a problem with which I don't know how to deal with: After choosing my
>> structural and statistic model (combined residual error model) I
>> estimated
>> the covariance matrix by including an OMEGA-BLOCK(4), which reduced the
>> OFV by 15. The correlations between the parameters were all estimated to
>> be minor (< 0.8). But when I model with a BLOCK(2) on VSS and V1, which
>> I
>> would expect to be positively correlated, the correlation is estimated
>> to
>> be -0.99. Additionally, the inclusion of BLOCK(2) does not significantly
>> improve the OFV.
>> So does it, after all, still make sense to include the BLOCK(2)?
>> Generally, at which step of model-building would you recommend to test
>> for
>> parameter correlation?
>>
>> Thanking you in advance,
>>
>> Hauke
>>
>> -----------------------------
>> Hauke Rhs
>>
>> Apotheker
>> Pharmazeutisches Institut
>> - Klinische Pharmazie -
>> An der Immenburg 4
>>
>> 53121 Bonn
>>
>> Tel: + 49-(0)228 73-5781
>> Fax: + 49-(0)228 73-9757
>>
>> www.klinische-pharmazie.info
>>
>>



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Received on Tue Aug 04 2009 - 05:24:25 EDT

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