Nele,
I agree with Leonid with these additional remarks:
1. The UNCONDITONAL option may still fail to produce covariance step output
2. bootstrap estimates of var-cov are more likely to be appropriate for
future predictions
3. the use of priors will always introduce a more approximate impression
of what you already know
Nick
On 15/10/2011 10:01 a.m., Leonid Gibiansky wrote:
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 Käßner
PK/PD Sciences
Modelling and Simulation (RDP/MS)
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Nick Holford, Professor Clinical Pharmacology
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