Piece-wise PD model
NMusers,
In a somewhat similar theme to Hauke's post, I am having an issue with
conditional assignment statements in $ERROR. I am trying to fit a piece-wise
PD model for a KPD system. A linear PD model is ok, but saturating models,
while I expect these to provide a better fit, converge with parameters that
essentially replicate a linear model (tried Emax, Power, Exponential). My last
ditch attempt was to try a piece-wise model, with 2 linear slopes, estimating
the change point.
Something like this
$PK
...
CHANGE=THETA(.)
SLOPE1=THETA(.)
SLOPE2=THETA(.)
...
$ERROR
A(.)=AEFF ;amount in effect compartment
IF(AEFF.LT.CHANGE) THEN
SLOPE=SLOPE1
ELSE
SLOPE=SLOPE2
ENDIF
EFFECT=AEFF*SLOPE
I always find minimization is terminated early, and the gradient for CHANGE is
zero at first iteration. The gradient does have a value at subsequent
iterations, but the final estimate of CHANGE (at termination anyway) is usually
not far off the initial estimate...I suspect it is not actually being
estimated, just floating a bit. Even if I fix CHANGE to a reasonable value, I
see minimization is terminated early.
Is there some trick I am missing here? or is it not possible to estimate a
parameter within a conditional assignment statement in $ERROR?
(seems like you can do this in $PK when a covariate or time is used in the IF
statement)
Thanks for any help,
Brendan Johnson
GlaxoSmithKline, RTP