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RE: VPC with Mixture Model

From: Mats Karlsson <mats.karlsson>
Date: Tue, 14 Apr 2009 22:39:53 +0200

Hi Nck,

Exactly - when in simulation mode the correct assignment will take place.
Here however, was the question about stratifying the VPC based on the value
of the POSTHOC estimates based on the real data.

Mats

Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Box 591
751 24 Uppsala Sweden
phone: +46 18 4714105
fax: +46 18 471 4003


-----Original Message-----
From: owner-nmusers
Behalf Of Nick Holford
Sent: Tuesday, April 14, 2009 10:08 PM
To: nmusers
Subject: Re: [NMusers] VPC with Mixture Model

Mats,

A VPC relies on simulation alone - there is no estimation step.
Presumably if the population estimate of the % of poor metabolizers is
5% then NONMEM will simulate 5% of the population as a poor metaboliser.
There is no Bayesian 'posthoc' step hidden in the way that NONMEM does
simulations is there? I had assumed (but have never checked) that if one
tabulates the value of MIXEST obtained when using $SIM that the
proportion of MIXEST values would not be biased compared to the
population value.

Nck

Mats Karlsson wrote:
> Hi Leonid,
>
> I would not do it for just the reason you mention. I would not want to
> condition my VPC on the model results. Especially as we know that the
> subpopulation assignment suffer from the same problems as other empirical
> Bayes estimates. "Shrinkage" when it comes to subpopulation assignment
will
> have the consequence that the larger of (two) subpopulations having a
higher
> fraction of POSTHOC assignments than the Pmix estimate for that
> subpopulation. This is expected and I have often seen it. So you may well
> have a situation when the population estimate of poor metabolizers is 5%,
> but only 2% are allocated to this subpopulation by the EBE step.
>
> Best regards,
> Mats
>
>
> Mats Karlsson, PhD
> Professor of Pharmacometrics
> Dept of Pharmaceutical Biosciences
> Uppsala University
> Box 591
> 751 24 Uppsala Sweden
> phone: +46 18 4714105
> fax: +46 18 471 4003
>
>
> -----Original Message-----
> From: Leonid Gibiansky [mailto:LGibiansky
> Sent: Tuesday, April 14, 2009 9:06 PM
> To: Mats Karlsson
> Cc: 'Satyendra Suryawanshi'; nmusers
> Subject: Re: [NMusers] VPC with Mixture Model
>
> Hi Mats,
>
> Could you elaborate why you would not stratify based on the
> subpopulations? It seems perfectly reasonable for me to simulate from
> the model (including random assignment of subpopulations), and then
> compare "apples to apples": observed subpopulation versus simulated
> subpopulations. In your example of 5% poor metabolizers, I would plot
> observed poor metabolizers (as assigned by the model) versus simulated
> poor metabolizers (as simulated from the model). Indeed, poor
> metabolizers assignment would be defined by the model, so this VPC will
> be conditioned on the model posthoc EST prediction, but the remaining
> parts of the model would be tested by this procedure. If the model is
> good, VPC should provide good results. It is unclear to me how sensitive
> this procedure is to model misspecification (in general, I think VPC is
> less sensitive to model misspecification than other model diagnostics)
>
> Thanks
> Leonid
>
> --------------------------------------
> Leonid Gibiansky, Ph.D.
> President, QuantPharm LLC
> web: www.quantpharm.com
> e-mail: LGibiansky at quantpharm.com
> tel: (301) 767 5566
>
>
>
>
> Mats Karlsson wrote:
>
>> Dear Satyendra,
>>
>>
>>
>> Interesting question. I don't think there is much written about this,
>> but I may be wrong. What I would not do is to try to stratify based on
>> estimated subpopulation allocation ("EST"). Rather I would use the same
>> VPCs as if there had been no mixture model. Possibly what you could do
>> is be more careful in your choice of prediction intervals to display.
>> For example, if you have a subpopulation of poor metabolizers of about
>> 5%, displaying only median and interquartile range PIs may not be a good
>> idea.
>>
>>
>>
>> Best regards,
>>
>> Mats
>>
>>
>>
>> Mats Karlsson, PhD
>>
>> Professor of Pharmacometrics
>>
>> Dept of Pharmaceutical Biosciences
>>
>> Uppsala University
>>
>> Box 591
>>
>> 751 24 Uppsala Sweden
>>
>> phone: +46 18 4714105
>>
>> fax: +46 18 471 4003
>>
>>
>>
>> *From:* owner-nmusers
>> [mailto:owner-nmusers
Suryawanshi
>> *Sent:* Tuesday, April 14, 2009 6:50 PM
>> *To:* nmusers
>> *Subject:* [NMusers] VPC with Mixture Model
>>
>>
>>
>> Dear all,
>>
>> I have a Mixture Model with 2 subpopulation. Now I want to check its
>> prediction. One way to see this is a Visual Predictive Check. My
>> question is, How to perform visual predictive check with mixture model?
>>
>> I will be thankful for your suggestion and references.
>>
>>
>>
>> Best regards
>>
>>
>>
>> Satyendra Suryawanshi, PhD
>>
>> University of Tennessee Health Science Center
>>
>>
>>
>>
>
>

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford
mobile: +33 64 271-6369 (Apr 6-Jul 17 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Tue Apr 14 2009 - 16:39:53 EDT

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