Thanks to all for your comments, I didn't expect so much.
If the occasion correspond to a specific dose (i.e. 1st dose or later)
then the question is, shall we expect a variability related to the
duration of the treatment? In that case, we will have as many
occasions as doses. The number of
Hi Steve,
I think we can apply some mechanistic insight into IOV in most cases. For
example for absorption parameters, it is difficult to see that anything but
each dosing occasion would constitute a separate occasion. There may however
be situations where it is difficult to judge properly and
Steve,
I understand that BOV can be a nuisance for designers :-)
However, arbitrary is not the same as practical. An arbitrary occasion
interval e.g. 1 hour or 1 year, would have no practical application for
any real drugs I know about.
But from a practical perspective for TCI an occasion du
Nick
While I agree that BOV is not solely a nuisance parameter it is a design
specific parameter and hence can be somewhat of a nuisance. By design specific
we can formulate settings in which the design of the study changes the estimate
of BOV.
To estimate the variance between occasions the d
Thierry,
Between subject variability (BSV aka IIV) and within subject variability
(WSV aka IOV) describe the limits of what we can identify as sources of
variability.
I don't consider this a nuisance -- it is an opportunity for learning.
The random assumption used for estimation of WSV is a
Ann,
Because you already log-tranformed your data, you may want to change
SIG1*IPRED to SIG1 for DUM.
I'm guessing the combination of ALAG and SIG1*IPRED is causing problem.
DUM = (LOQ-IPRED)/(SIG1)
Best regards,
Shelley
Xiao Hu (Shelley), Ph.D.
Scien
Ann,
Several ideas:
1. Fix ALAGs to zero, will it help?
2. Try to shield IPRED from being zero
IPRED=LOG(0.0001)
IF(F.GT.0.0001) IPRED=LOG(F)
Y=IPRED + SIG1*ERR(1)
(this could be a bad style, but will allow you to test the code)
3. Try ADVAN6, 8, 13
4. Remove BQL part, fit it as a 3-comp linea
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Dear Matt & All
I'm still battling I'm afraid...
Can't seem to get past the SUM OF "SQUARED" WEIGHTED INDIVIDUAL RESIDUALS IS
INFINITE problem.
I've now log-transformed my data, and deleted all but the first occurrence of a
BQL data point from each individual. I'm confident that the initial e
Dear Thierry,
The article below nicely describes the importance of incorporating IOV since
it otherwise might lead to a falsely optimistic impression of the potential
value of TDM.
Karlsson MO, Sheiner LB. The importance of modeling interoccasion
variability in population
pharmacokinetic a
Dear James,
I always thought that intra-individual variability (IIV) classically
represented the immovable limit on the gains to be expected from TDM - IOV
being indeed used only in a minority of population PK analyses. Both intra- and
inter-occasion variability actually represent nuisance. We
Hi Thierry,
Actually, devising a TDM program is precisely when you should be evaluating
whether you have substantial IOV. If IOV is considerably greater than IIV
then there is little benefit in a TDM program as you point out since a
concentration from one occasion may not contain much informat
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Hi Nicolas
My short answer would be another question: "what is the aim of your analysis ?"
IOV is fine to split variability into inter-individual,
intra-individual-inter-occasion and intra-individual-intra-occasion random
components. This is excellent for data description, and can bring interest
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