中药新药临床试验中安慰剂模拟效果评价与思考

Evaluation and thinking of simulation effect of placebo on new drug clinical trials of traditional Chinese medicines

目的探讨中药新药临床试验中安慰剂的模拟效果评价方法和盲法的实施问题,为提高中药双盲临床试验的研究质量提供方法学参考。方法以一个中药新药安慰剂的制作为实例,从形、色、味、气几个方面,通过进行试验药物的可能性判断和安慰剂与试验药的相似性判断,评价中药安慰剂的模拟效果,并分析中药临床试验盲法实施中存在的实际问题。结果评价者对于两种药物是否是试验药物的可能性判断无统计学差异(P>0.05);对于安慰剂与试验药的相似性,两药在外观的评分差异无统计学意义(P>0.05),其一致性达到100%,但安慰剂在颜色、气味、口味上与试验药比较差异均有统计学意义(P<0.05),其一致性分别为50%、10%和15%。结论中药安慰剂在色、气、味上有时很难与试验药完全一致,因此,在试验实施过程中要加强受试者和研究者的依从性管理,减少破盲;在试验结束后评估破盲对试验结果的影响。

Objectives To discuss the methodology of evaluation of traditional Chinese medicine （TCM） placebo simulation effects and the problems of blind implementation and so as to improve the quality of double-blind clinical trials of TCM. Methods Focusing on case of placebo preparation of TCM investigational new drug, simulation effects of the placebo were evaluated in terms of shape, color, taste and smell. The possibility of placebo be a drug and the similarity between placebo and drug were tested. Results There was no significant difference between placebo and investigational new drug to be judged as a drug （P〉0.05）. As for the similarity between placebo and drug, there was no significantly difference of the shape （P〉0.05）, for which the similarity was 100%. The color, taste and smell were significant different between placebo and drug （P〈0.05）, for which the similarity were 50%, 10% and 15% respectively. Conclusions It is very difficult to simulate TCM based on its certain color, taste or smell. Therefore, the subjects and the investigators＇ compliance should be kept to avoid breaking the blind intentionally in the process of the trial and the influence of unblinding should be estimated at the end of the trial.