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RE: Very small P-Value for ETABAR

From: Wang, Yaning <>
Date: Thu, 13 Nov 2008 11:54:54 -0500

Another possible reason could be that you have a huge number of subjects
in your database. Then a tiny deviation from zero will generate a highly
significant p-value (very small). You should look at the estimate itself
too (ETABAR).

Yaning Wang, Ph.D.
Team Leader, Pharmacometrics
Office of Clinical Pharmacology
Office of Translational Science
Center for Drug Evaluation and Research
U.S. Food and Drug Administration
Phone: 301-796-1624

"The contents of this message are mine personally and do not necessarily
reflect any position of the Government or the Food and Drug



From: owner-nmusers
On Behalf Of Jian Xu
Sent: Thursday, November 13, 2008 11:32 AM
To: Denney, William S.; NM Users
Subject: Re: [NMusers] Very small P-Value for ETABAR

Hi, Bill,
Thanks for your input. I also got some answers from Mahesh, Yaning, and
Pankaj. Thank you guys!
This small P-value for ETABAR could be due to possible two reasons:
1: As Bill and Yaning suggested, this ETA is non-nomal distribuated,
which could result from covariates (e.g. gender) or mixture of
population (e.g. race)
2: As Mahesh and Pankaj suggested, the shrinkage of this ETA needs to be
calculated, which can help identify whether the model is ill
conditioning or overparameterized .



From: Denney, William S. <william_denney
To: Jian Xu <alanub
Sent: Thursday, November 13, 2008 10:41:15 AM
Subject: RE: [NMusers] Very small P-Value for ETABAR

Hi Jian,
I would look for a covariate effect on that parameter.


From: owner-nmusers
On Behalf Of Jian Xu
Sent: Thursday, November 13, 2008 10:16 AM
To: nmusers
Subject: [NMusers] Very small P-Value for ETABAR

A few years back, there was a discussion on the P-value for ETABAR.
However, I am not sure how to appropriately handle very small P-value(s)
for ETABAR situation during the development of a model.
I need some clarifications to a few questions:
1: Should we just ignore this small P-Value warning?
2: Can we change IIV model to avoid small P-value for ETABAR? Or any
other suggestions?
3: Does NONMEM make any assumptions on ETA distribution?
This P-value for ETABAR really bugs me a lot. I look forward to seeing
some input.
Thank you and I appreicate your time and help.

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Received on Thu Nov 13 2008 - 11:54:54 EST

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