S. Dutta et al., IS IT POSSIBLE TO ESTIMATE THE PARAMETERS OF THE SIGMOID E(MAX) MODELWITH TRUNCATED DATA TYPICAL OF CLINICAL-STUDIES, Journal of pharmaceutical sciences, 85(2), 1996, pp. 232-239
Many drug concentration-effect relationships are described by the nonl
inear sigmoid E(max) model. Clinical considerations frequently limit t
he magnitude of effect intensity that may be produced; the most pronou
nced effect intensity may be considerably below E(max). We have tested
and quantified the influence of this limitation on the estimatability
of the sigmoid E(max) model parameters. We have used the estimated pa
rameter values to calculate data descriptors (drug concentrations requ
ired to produce certain effect intensities) and compared these with co
ncentrations determined by using exact parameter values. We found that
when the highest measured effect intensity was less than 95% of E(max
), E(max) and EC(50) were poorly estimated (high coefficient of variat
ion and pronounced bias). Nevertheless, the fit to the data was quite
good and the data descriptors were estimated with precision within the
range for which data were available but not beyond. Baseline effect w
as estimated with good precision but the sigmoidicity parameter (gamma
) was highly variable. Thus, where clinical considerations prevent det
ermination of concentration-effect data near the maximum effect intens
ity, E(max) and EC(50) estimations are unreliable. The use of estimabl
e data descriptors is proposed to characterize the concentration-effec
t relationship under these conditions.