NONMEM Users Network Archive

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Re: PRIOR method without covariance matrix of estimates?

From: Leonid Gibiansky <LGibiansky>
Date: Fri, 14 Oct 2011 17:01:26 -0400

Nele,

Nonmem 7.2 has UNCONDITIONAL option in cov step that would compute SEs
even for problems with error in minimization.

Also, it is perfectly OK to have variance-covariance computed from
bootstrap; some may even argue that it is better than use Nonmem cov matrix.

And finally (just an opinion) I would rather combine the data than use
priors.

Thanks
Leonid


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



On 10/13/2011 1:31 AM, Kaessner, Nele wrote:
> Dear all,
>
> I am currently in a planning phase for a PopPK evaluation for an
> upcoming study. I have already developed a PopPK model for this
> compound, and the idea would now be to fit the available model to the
> new data. One idea was to do this via the PRIOR functionality in NONMEM,
> so that I do not have to mix the old data into the new data set. So now
> I wanted to test the performance of this approach via simulations, and
> have the following problem:
>
> My previously developed final model did not converge successfully
> (terminated with rounding errors), so I do not have a covariance matrix
> of estimates to describe the uncertainty in the THETAs. However I
> obtained confidence intervals from a nonparametric bootstrap, and I was
> wondering if these results can somehow be used instead for the prior
> information.
>
> In some internal discussions we had the idea to just use all the
> parameter estimates from the performed 1000 bootstrap runs, and just
> calculate variance and covariance of THETAs from these.
>
> I would highly appreciate your comments on the validity of such an
> approach, or suggestions of other alternatives.
>
> Thanks and best regards
>
> Nele
>
> ______________________________________________________________
>
> Dr. Nele Kner
>
> PK/PD Sciences
>
> Modelling and Simulation (RDP/MS)
>
> *Nycomed: A Takeda Company*
>
> Nycomed GmbH
>
> Byk-Gulden-Str. 2
>
> D-78467 Konstanz, Germany
>
> Fon: (+49) 7531 / 84 - 4759
>
> Fax: (+49) 7531 / 84 - 94759
>
> mailto: nele.kaessner
>
> http://www.nycomed.com <http://www.nycomed.com/>
>
> County Court: Freiburg, Commercial Register HRB 701257
>
> Chairman Supervisory Board: Charles Depasse (Speaker)
>
> Management Board: Gilbert Rademacher (Speaker),
> Konstantin von Alvensleben, Dr. Rainer Wiartalla
>
>
>
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Received on Fri Oct 14 2011 - 17:01:26 EDT

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