NONMEM Users Network Archive

Hosted by Cognigen

Re: VPC with Mixture Model

From: Nick Holford <n.holford>
Date: Tue, 14 Apr 2009 22:07:32 +0200

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
>> *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 - 16:07:32 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.