【摘要】 基于比例优势模型的临床试验仿真,给出优化试验设计方法,以抗偏头痛新药那拉曲坦(naratriptan)为例,仿真药物临床试验结果。采用比例优势模型,分析不同给药时间、剂量对疼痛减轻(painrelief,PR)的影响。然后,采用优化实验设计最大化FIM行列式,比较临床试验仿真的设计结果,得出较合理的给药剂量和时间的设计方案。通过曲线图直观地表示出PR概率的变化趋势,反映了给药时间和给药剂量对PR产生的影响。从仿真结果得出,药物效应的变化滞后于血药浓度的变化,疼痛减轻概率和给药剂量、采样时间、模型参数等因素有关。临床实验仿真对于新药的研发是一种有效的工具,它可以定量估计可控因素对治疗效果的影响。更多还原

【Abstract】 To introduce the clinical trial simulation based on proportional odds model.Taking naratriptan as example,which is a novel agonist for the acute treatment of migraine,we adopted the method of D-optimal design to simulate the drug clinical trail of naratriptan.We adopted proportional odds model and analysed different factors such as time and does how to impact Pain Relief(PR).Then,the D-optimal design was used to maximize the determinant of Fisher information matrix(FIM) and compared the clinical trial simulated results.Finally more reasonable dose and time of the designs were obtained.The curve of the PR probability expressed PR trend directly,reflecting administration dose and time on the impact of PR.According to the simulated results,we found that there was a delay of the effect with respect to the plasma concentration in "effect" compartment and the probability of having a specific Pain Relief(PR) score depended on different facts such as dose,the effect sampling time and model parameters.Clinical trial simulation is a useful tool for the new drug development and it can be used for the quantitative assessment of the controllable factors to the effect of treatment.更多还原