Estimating the Parameters of the Operational Model of Pharmacological Agonism
Centre for Mathematical Sciences
Lund Institute of Technology,
The aim of this work is practical. We show that the parameters of the widely
used operational model of pharmacological agonism are impossible to estimate
from single dose-response curves. The parameters can be estimated using pairs
of dose-response curves (usually treatment and control) sharing some parameters.
Confidence bands for the estimators are developed. In the case of multiple
dose-response curve pairs one can employ a nonlinear mixed effects model
to allow for inter-individual variation. The point estimates and the confidence
intervals thus obtained are similar to the more naive construction based
on mean and standard errors of parameter estimates. To test for difference
of certain parameters between treatment and control we employ a permutation
Dose-response curves, concentration-response curves, operational model of
agonism, confidence interval, mixed effects.