Dear all,
Thanks for your kind advice. I tried to dig out the solution based on your
suggestion except for the demol definition, but unfortunately I can't identify
any possible cause for the error message. There is no error in covariance
step, estimated standard errors are within normal range
Jakob,
Thanks for some more info on this issue. I have seen work from Mats and
Rada that says ETABAR can be biased when there is a lot of shrinkage
even when the data is simulated and fitted with the correct model. Can
you confirm this and can you explain how it arises? In the worst case of
s
Dear all,
First of all, I am not sure that there is any assumption of etas having
a normal distribution when estimating a parametric model in NONMEM. The
variance of eta (OMEGA) does not carry an assumption of normality. I
believe that Stuart used to say the assumption of normality is only when
si
Dear All,
Realized etas (EBEs, MAPs) is estimated under the assumption of normal
distribution.
However, the resultant distribution of EBEs may not be normal or mean of
them may not be 0.
To pass t-test, one may use "CENTERING" option at $ESTIMATION.
But, this practice is discouraged by some (and I
Hi Xia,
Just to clarify one thing (I agree with almost everything you said):
The p-value indeed is related to the test of ETABAR=0. However, this is
not a test of normality, only a test that may reject the mean of the
etas being zero (H0). Therefore, shrinkage per se does not lead to
rejection of
Dear All,
Just some quick statistical points...
P value is usually associated with hypothesis test. As far as I know, NONMEM
assume normal distribution for ETA, ETA~N(0,omega), which means the null
hypothesis to test is H0: ETABAR=0. A small P value indicates a significant
test. You reject the
Hi, All,
This is just brief my understanding.
If common variable IRSET (a kind of reset indicator variable) is set to
1, this error message shows.
This variable is set with various conditions but without minimization
failure.
The condition I found is that
IRSETP==1 or IRSET > 0.1*ITN or (IRES
Jian,
ETABAR p-value could be a useful quick check of the results, but it
should not be used to replace the graphical evaluation of the model.
Graphical evaluation should always include the histograms of the random
effects, QQ plot of the random effects versus standard normal
distribution, sca
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 Cl
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) o
Hi Jian,
As Bill says, including a covariate may fix your problem. However, two
other underlying problems may also be causing this:
1. Asymmetric shrinkage of the eta. Two examples of this that I
have seen is if you have an eta on epsilon (different residual-error
magnitude in different subje
You might want to look at the shrinkage for the eta in question.
Regards,
Pankaj
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Denney, William S.
Sent: Thursday, November 13, 2008 10:41 AM
To: Jian Xu; nmusers@globomaxnm.com
Subject: RE: [
Dear Mark,
Do you really trust ECC unit? If my DRAM is damaged, I will live in an
apparently random world when ECC is working. :)
Best regards,
Guangli
Background, Most modern computers use a system called ECC (Error checking/correction) wherein each memory location has an extra bit (the parity bit) that is used for checking whether the data location is "correct". Interestingly, data bits in memory can actually change randomly, due to electro m
Mitsuo,
This is a new message specific to NONMEM VI. I must confess I don't know
what to make of this message myself. It would be informative if someone
could tell us what internals in NONMEM trigger this message (i.e., "PROBLEMS
OCCURRED WITH THE MINIMIZATION").
With respect to your two model
Hi Jian,
I would look for a covariate effect on that parameter.
Thanks,
Bill
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Jian Xu
Sent: Thursday, November 13, 2008 10:16 AM
To: nmusers@globomaxnm.com
Subject: [NMusers] Very small P-Value fo
Dear NMUSERS,
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
Dear Mitsuo
This previous, quite comprehensive post by William Bachman (orig. Ken
Kowalski) may help to interpret the COV-step.
http://www.cognigencorp.com/nonmem/nm/99may012003.html
Best regards
Martin Fransson
> -Original Message-
> From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
>
Dear Mitsuo,
This error message pops up with me more often. I routinely work with
small datasets and hence less stable estimation. In my experience I
encounter mainly three situations after this message:
1. Covariance step fails (so the message can be ignored as Nick
suggested)
2. Covariance step
Mitsuo,
I have no idea how to decide if the covariance matrix is reasonable or
not. I leave that to statisticians who are trained to see patterns in
random numbers.
The question of what to do with bootstrap results has been well
investigated in the past. The answer is just ignore all NONMEM'
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