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The main mis
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Dear NONMEM users,
My goal was to add a drug effect to a disease progression model in a way that
the drug effect is different when a certain threshold concentration is exceeded
(similarly to modeling a 'hockey-stick' when performing covariate analysis).
First, I did it in the following way (par
Hi Benjamin
I think the problem was that when nonmem tested small variations of
THETA(1) in the first version, nothing changed in the OF as these
variation have not resulted in the change in the IF conditions (e.g., if
your data contained WCMIN values 1 and 2 and nothing in between, and
THETA(
Hi Leonid. Thanks for your quick response. WCMIN is continuous. In fact, it is
actually identical to CONC (forgot to change it while simplifying). Any
thoughts on this?Ben
- Originalnachricht -
Von: Leonid Gibiansky [mailto:lgibian...@quantpharm.com]
Gesendet: Thursday, September 19, 201
Benjamin.
Even as WCMIN is continuous by nature, it is not continuous in the
dataset (at observation points). You may look at your WCMIN values in
the data file (I assume this values are in the data file?) and see where
the initial conditions for THETA(1) placed in that range. Step for
gradien
Sorry, there was a typos in the code, here is the version with
continuous SLOPE function
IF(CONC.LE.THRESH) SLOPE = THETA(3)+THETA(4)*CONC+ETA(2)
IF(CONC.GT.THRESH) SLOPE =
THETA(3)+THETA(4)*THRESH+THETA(5)*(CONC-THRESH)+ETA(2)
Then, if you rename
NEWTHETA3 = THETA(3)+THETA(4)*THRESH
you will
Hi Benjamin,
You should not use the closed form code for a linear model to disease
progression if the slope is varying with time. See slide 9:
http://holford.fmhs.auckland.ac.nz/docs/clinical-pharmacology-equals-disease-progress-plus-drug-action.pdf
In your case the slope is dependent on WCMI
Dear Benjamin and Leonid,
Although a steep sigmoidal Emax function often works well to approximate a
step function, the rate of change is quite dependent on the value of the X
variable. Another function (below) has some advantages. For details, see
Henin et al., AAPS J. 2012 Jun;14(2):155-63.
A
