Jakob,
I'm not sure that I would have confidence in the findings of
fixed-effect) interaction component between WT and CRCL (with the hope
of concluding it is not needed) approach. I know we tend to think in
this type of sequential manner with respect to covariate relationship
testing but, as
Jakob,
Restrictions on the parameter values is not the only (and not the major)
problem with additive parametrization. In this specific case, CRCL (as
clearance) increases proportionally to WT^(3/4) (or similar power, if
you accept that allometric scaling has biological meaning or that the
*I'm very interested in comments from the group, since these issues are
very confused in the literature.
Schwartz equation:* CrCl (ml/min/1.73m2)= [length (cm) x k] / Scr
(Patient population: infants over 1 week old through adolescence (18
years old)) k = 0.45 for infants 1 to 52 weeks
Leonid,
You propose two models
Model 1: TVCL=THETA(1)*(WT/70)^(3/4) + THETA(2)*(WT/70)^(3/4)
Model 2: TVCL=THETA(1)*(WT/70)^(3/4) * (CRCL/BSA)^GAMMA
As you say, Model 1 clearly is not identifiable to distinguish THETA(1)
and THETA(2). An identifiable model would be:
Model 3:
Nick,
Just to set the record straight:
I did NOT proposed model (1):
TVCL=THETA(1)*(WT/70)^(3/4) + THETA(2)*(WT/70)^(3/4)
Rather I mentioned that this is not an appropriate model.
Model 2 is indeed empirical. Instead of BSA you can use WT^(3/4) or any
other normalization:
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A Pharmacokineticist is needed for large pharmaceutical company. This scientist
will have a PhD, Pharm D. MD or equivalent along with 2 years of hands on
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Jakob,
The model that I mentioned is not additive; it is multiplicative:
Parameter= MeanValue*Effect1(WT)*Effect2(RF)
but the effect of RF is expressed as a linear function of RF
Effect2(RF) = 1 + THETA()*RF
Leonid
--
Leonid Gibiansky, Ph.D.
President,
