今日の論文

• Ishibashi, Yano, and Oguma (2003) BJCP, "Population pharmacokinetics of platinum after nedaplatin administration and model validation in adult patients"
  • 解析バリデーションについて

In this study, we applied the objective function mapping method to analyse parameter sensitivity, as well as bootstrap resampling and data splitting to examine the validity of the parameter estimates.
The objective function mapping method was applied to confirm the parameter stability, sensitivity, and to determine the shape of the parameter space. By fixing the parameter value of interest to ±5, 10, 15, 20, 30, 40, and 60% of its population estimate, other parameters were re-estimated by NONMEM*1. Changes in the objective function (ΔOBJ) for each re-estimation were plotted. The plots of ΔOBJ for each parameter were then fitted by a polynomial equation (three orders). Assuming the χ² distribution for ΔOBJ, the values for a parameter which corresponds to ΔOBJ = ±3.84 represent 95% confidence limits for the parameter.

• • これはもちろん，'log-likelihood profile' 法とも呼ばれる方法で，引用されている Holford & Peace の ProNAS の論文でもその言葉が使われています．

*1:Holford & Peace (1992) ProNAS, "Results and validation of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine"