Magnusdottir Bergrun T
Statistiska institutionen, Stockholms universitet, SE-106 91 Stockholm, Sweden.
Biom J. 2016 May;58(3):518-34. doi: 10.1002/bimj.201400203. Epub 2015 Oct 15.
The aim of dose finding studies is sometimes to estimate parameters in a fitted model. The precision of the parameter estimates should be as high as possible. This can be obtained by increasing the number of subjects in the study, N, choosing a good and efficient estimation approach, and by designing the dose finding study in an optimal way. Increasing the number of subjects is not always feasible because of increasing cost, time limitations, etc. In this paper, we assume fixed N and consider estimation approaches and study designs for multiresponse dose finding studies. We work with diabetes dose-response data and compare a system estimation approach that fits a multiresponse Emax model to the data to equation-by-equation estimation that fits uniresponse Emax models to the data. We then derive some optimal designs for estimating the parameters in the multi- and uniresponse Emax model and study the efficiency of these designs.
剂量探索研究的目的有时是估计拟合模型中的参数。参数估计的精度应尽可能高。这可以通过增加研究中的受试者数量N、选择良好且有效的估计方法以及以最优方式设计剂量探索研究来实现。由于成本增加、时间限制等原因,增加受试者数量并不总是可行的。在本文中,我们假设N固定,并考虑多响应剂量探索研究的估计方法和研究设计。我们使用糖尿病剂量反应数据,并将一种将多响应Emax模型拟合到数据的系统估计方法与将单响应Emax模型拟合到数据的逐个方程估计方法进行比较。然后,我们推导了一些用于估计多响应和单响应Emax模型中参数的最优设计,并研究了这些设计的效率。