RE: medians of the simulation in VPC are systematically below the medians of the observations when the model fit looks fine.
Hi Shirley,
What this suggests is that the distributions of the empirical Bayes'
predictions of the ETAs (which are used to generate the IPREDs) have some
departures from the normality assumptions (including zero mean with constant
variance omega^2) when you use the model in simulations. I suggest that you
look at box plots of the ETAs for each parameter stratified by key features
of the design such as dose and generate histograms of the ETAs to verify
that the distributions are symmetrically distributed about zero. If you
observe departures from the normality assumptions that are being used in
your simulations (e.g., trends in ETAs versus dose, right-skewed
distribution, etc.) this may provide some insight as to where the
deficiencies lie in your model. While I agree that ETA predictions are an
imperfect diagnostic since they can suffer from shrinkage, as long as you
continue to use simulations and a VPC approach to verify the adequacy of
your model, a cautious look at these ETA plots to provide some guidance as
to how to modify your model to improve the VPC may be helpful.
Best regards,
Ken
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Hou, Xiaoli Shirley
Sent: Friday, February 03, 2012 5:48 PM
To: nmusers
Subject: [NMusers] medians of the simulation in VPC are systematically below
the medians of the observations when the model fit looks fine.
Dear All,
I have built a non-compartment model, in which the medians of IPREDs and
Observations are very close. But in VPC plot, the medians of simulations
are systematically below the medians of observations
Any idea why it happens?
Thanks.
Shirley
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