IS IT POSSIBLE TO ESTIMATE THE PARAMETERS OF THE SIGMOID E(MAX) MODELWITH TRUNCATED DATA TYPICAL OF CLINICAL-STUDIES

Citation
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
Citations number
40
Categorie Soggetti
Chemistry,"Pharmacology & Pharmacy
ISSN journal
00223549
Volume
85
Issue
2
Year of publication
1996
Pages
232 - 239
Database
ISI
SICI code
0022-3549(1996)85:2<232:IIPTET>2.0.ZU;2-8
Abstract
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.