基于条件加权似然方法的BOIN12设计的改进研究

Improved BOIN12 Design based on Conditional Weighted Likelihood Method

目的基于条件加权似然方法对BOIN12设计进行改进,解决试验药物毒性和有效性出现延迟的情况下的最优剂量探索问题。方法利用条件加权似然方法给出延迟情况下的似然函数,对毒性率和条件有效率进行估计。通过模拟将改进后的BOIN12设计与其他Ⅰ-Ⅱ期设计方法进行比较,评估其性能。结果模拟研究表明,在多个不同场景下,改进后的设计仍然具有优良的统计性能,同时大大缩短了试验时长。结论改进后的设计可以解决Ⅰ-Ⅱ期试验中的毒性和有效性同时延迟问题。

Objective The BOIN12 design was improved based on conditional weighted likelihood method to solve the optimal dose exploration in the case of delayed toxicity and efficacy of drugs.Methods The conditional weighted likelihood method was used to estimate the toxicity rate and conditional efficacy rate.The improved BOIN12 design was compared with other phase I-II design through simulation to evaluate its performance.Results Simulation results show that the improved design still has excellent statistical performance in different scenarios and the trial duration is greatly shortened.Conclusion The improved design can addresses both toxicity and efficacy delays in phase I-II trials.