Fitting Emax models to clinical trial dose-response data

被引:23
作者
Kirby, Simon [1 ]
Brain, Phil [1 ]
Jones, Byron [1 ]
机构
[1] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England
关键词
clinical trial; dose-response; E-max model; model selection; non-linear model; DESIGNS;
D O I
10.1002/pst.432
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We consider fitting E-max models to the primary endpoint for a parallel group dose-response clinical trial. Such models can be difficult to fit using Maximum Likelihood if the data give little information about the maximum possible response. Consequently, we consider alternative models that can be derived as limiting cases, which can usually be fitted. Furthermore we propose two model selection procedures for choosing between the different models. These model selection procedures are compared with two model selection procedures which have previously been used. In a simulation study we find that the model selection procedure that performs best depends on the underlying true situation. One of the new model selection procedures gives what may be regarded as the most robust of the procedures. Copyright (C) 2010 John Wiley & Sons, Ltd.
引用
收藏
页码:143 / 149
页数:7
相关论文
共 11 条
[1]  
[Anonymous], 2007, R LANG ENV STAT COMP
[2]  
Bates D. M., 1988, Nonlinear regression analysis and its applications, V2
[3]   Innovative approaches for designing and analyzing adaptive dose-ranging trials [J].
Bornkamp, Bjoern ;
Bretz, Frank ;
Dmitrienko, Alex ;
Enas, Greg ;
Gaydos, Brenda ;
Hsu, Chyi-Hung ;
Koenig, Franz ;
Krams, Michael ;
Liu, Qing ;
Neuenschwander, Beat ;
Parke, Tom ;
Pinheiro, Jose ;
Roy, Amit ;
Sax, Rick ;
Shen, Frank .
JOURNAL OF BIOPHARMACEUTICAL STATISTICS, 2007, 17 (06) :965-995
[4]   Optimal Designs for Dose-Finding Studies [J].
Dette, Holger ;
Bretz, Frank ;
Pepelyshev, Andrey ;
Pinheiro, Jose .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 2008, 103 (483) :1225-1237
[5]   Is it possible to estimate the parameters of the sigmoid E(max) model with truncated data typical of clinical studies? [J].
Dutta, S ;
Matsumoto, Y ;
Ebling, WF .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1996, 85 (02) :232-239
[6]  
KIRBY S, 2010, J BIOPHARM STAT, V20, P5
[7]  
Morgan BJT., 2000, APPL STOCHASTIC MODE
[8]  
Ratkowsky D. A., 1983, Nonlinear regression modeling
[9]  
Ross G.J.S., 1990, NONLINEAR ESTIMATION
[10]   Estimating potency for the Emax-model without attaining maximal effects [J].
Schoemaker, RC ;
van Gerven, JMA ;
Cohen, AF .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1998, 26 (05) :581-593