Optimal Serial Dilutions Designs for Drug Discovery Experiments

被引:3
作者
Donev, Alexander N. [1 ]
Tobias, Randall D. [2 ]
机构
[1] Univ Manchester, Sch Math, Manchester M13 9PL, Lancs, England
[2] SAS Inst Inc, Linear Models R&D, Cary, NC USA
关键词
Bioassay; Dose-response study; High-throughput screening; Minimum significant difference; Population D- and DS-optimality; ASSAYS; BIOASSAY;
D O I
10.1080/10543406.2010.481801
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Dose-response studies are an essential part of the drug discovery process. They are typically carried out on a large number of chemical compounds using serial dilution experimental designs. This paper proposes a method of selecting the key parameters of these designs (maximum dose, dilution factor, number of concentrations and number of replicated observations for each concentration) depending on the stage of the drug discovery process where the study takes place. This is achieved by employing and extending results from optimal design theory. Population D- and DS-optimality are defined and used to evaluate the precision of estimating the potency of the tested compounds. The proposed methodology is easy to use and creates opportunities to reduce the cost of the experiments without compromising the quality of the data obtained in them.
引用
收藏
页码:484 / 497
页数:14
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