Bogacka Barbara, Patan Maciej, Johnson Patrick J, Youdim Kuresh, Atkinson Anthony C
School of Mathematical Sciences, Queen Mary, University of London, London, United Kingdom.
J Biopharm Stat. 2011 May;21(3):555-72. doi: 10.1080/10543406.2010.489979.
We find closed-form expressions for the D-optimum designs for three- and four-parameter nonlinear models arising in kinetic models for enzyme inhibition. We calculate the efficiency of designs over a range of parameter values and make recommendations for design when the parameter values are not well known. In a three-parameter experimental example, a standard design has an efficiency of 18.2% of the D-optimum design. Experimental results from a standard design with 120 trials and a D-optimum design with 21 trials give parameter estimates that are in close agreement. The estimated standard errors of these parameter estimates confirm our theoretical results on efficiency and thus on the serious savings that can be made by the use of D-optimum designs.
我们找到了酶抑制动力学模型中出现的三参数和四参数非线性模型的D最优设计的闭式表达式。我们计算了一系列参数值下设计的效率,并针对参数值未知时的设计给出了建议。在一个三参数实验示例中,一个标准设计的效率为D最优设计的18.2%。一个有120次试验的标准设计和一个有21次试验的D最优设计的实验结果给出了非常接近的参数估计值。这些参数估计值的估计标准误差证实了我们关于效率的理论结果,从而也证实了使用D最优设计可以实现的显著节省。