自适应随机在具有响应延迟的临床试验中的应用评价  

Adaptive randomization for clinical trials with delayed response

作　　者：魏永越[1] 荀鹏程[1] 周敏林[1] 赵杨[1] 朱晶晶[1] 于浩[1] 陈峰[1] 

机构地区：[1]南京医科大学公共卫生学院流行病与卫生统计学系

出　　处：《中国临床药理学与治疗学》2010年第9期1040-1045,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：江苏省自然科学基金资助(BK2008449)

摘　　要：目的:探讨在试验结果具有延迟特征的临床试验中,自适应随机的应用条件及效果评价。方法:通过模拟试验,考察不同有效率水平、率差水平、不同延迟程度下,从较优组(A组)的样本构成比、平均减少失败人数及检验效能等角度,考察改良的随机化胜者优先(MRPW)原则的应用条件及随机效果。结果:当两组率差较小时:若有效率较低,不同延迟程度对MRPW的效果影响甚微,随着率的增大,延迟效应对MRPW的效果的影响逐渐显现;当两组率差较大时:随着延迟时间的增大,MRPW的效果衰减趋势明显,且成功率越高,下降趋势越明显。若以MRPW的效果下降不超过20%为限,则当成功率及率差较低时,对延迟时间的限制较为宽松,率差及成功率越大,对延迟时间限制越严格。结论:在具有延迟效应的临床试验中,MRPW仍有一定的应用价值。若延迟时间满足一定的条件,则可保证其随机效果,从而扩展了其应用条件。实际临床试验中,应根据具体的参数情况,探讨延迟效应对自适应随机效果的影响,从而决定MRPW是否适用于该试验。AIM：To discuss the application condition and evaluate the effect of the adaptive randomization in clinical trials with delayed response. METHODS：The statistical simulations were conducted to evaluate the modified randomized play-the-winner（MRPW） rule and to explore its application condition in clinical trials with delayed response.All the tests were done under circumstances of different effective rates,different levels of rate differences between groups and different delayed levels of response.The proportion of the sample size of the superior group（Group A）,the average reduced failure number and the power were also considered during the evaluation.RESULTS：When the rate difference between two groups was small,with relatively low effective rate,different delayed levels had little impact on the effect of MRPW.As effective rate went up,delayed effect on MRPW gradually emerge.When the rate difference between two groups was relatively high,with the increase of delayed time,the weakening tendency of effects on MRPW was obvious.This trend was more obvious in condition of higher effective rate.If the application criterion was set as that the reduction of average reduced failure number should be in the upper limit of 20%,the restriction of delay was less stringent in the condition of lower effective rate,while this restriction was rigorous when effective rates and the difference between effective rates were higher.CONCLUSION：The study extends the application of MRPW in clinical trials with delayed response,which shows that the results of MRPW fit the demand when the delay degree is in some region.According to specific parameters and delayed levels of response in actual clinical trial,we should explore the effect of MRPW to discuss whether to conduct the MRPW in such trial.

关 键 词：自适应随机 随机化胜者优先原则 延迟效应 

分 类 号：R311[医药卫生—基础医学]