ASSESSMENT OF THE GLOBAL 2-STAGE METHOD TO EC50 DETERMINATION

Preclinical studies of a new drug supply sets of concentration-effect observations. For each experiment, EC50 is estimated through fitting o f the E-max model. Naive pooling of these individual estimates, also c alled the Standard Two-Stage method (STS), is usually performed. A bet ter combination is obtained by the Global Two-Stage method (GTS) which takes into account the variability of the nonlinear regression estima tion errors. The performances of STS and GTS are compared on real and simulated data. The results show that GTS performs better than STS in terms of bias or RMSE, especially in case of poorly designed experimen ts. Degradation of the quality of STS results in simulations appears t o be mainly due to some experiments that are usually rejected by exper imenters. Such rejections are avoided when using GTS, which hence is p articularly suitable for systematic treatment of this kind of data. (C ) 1998 Elsevier Science Inc.