倍比分组双盲随机对照试验的盲态分析

doi:10.12092/j.issn.1009-2501.2019.10.011

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (10): 1155-1160.doi: 10.12092/j.issn.1009-2501.2019.10.011

倍比分组双盲随机对照试验的盲态分析

刘雅琦^1,2，陆梦洁²，刘玉秀^1,2,3，陈羽³，袁阳丹³，周憧憧^1,2，刘曼^1,2

¹南京医科大学公共卫生学院生物统计学系，南京 211166，江苏；²东部战区总医院（原南京军区南京总医院）医学统计学教研室，南京 210002，江苏； ³南方医科大学公共卫生学院生物统计学系，广州 510515，广东

收稿日期:2019-04-19 修回日期:2019-05-09 出版日期:2019-10-26 发布日期:2019-10-28
通讯作者: 刘玉秀，男，教授，主任医师，研究方向：临床试验中的统计理论与方法。 Tel:13952043658 E-mail:liu_yuxiu@163.com
作者简介:刘雅琦，女，硕士，研究方向：临床试验中的统计理论与方法。 Tel:18351975160 E-mail:liuyaqi@njmu.edu.cn
基金资助:
国家自然科学基金青年基金（81803338）

Blinded analysis of double-blind randomized controlled trial for unequal integer ratio grouping

LIU Yaqi ^1,2, LU Mengjie², LIU Yuxiu ^1,2,3, CHEN Yu ³, YUAN Yangdan³, ZHOU Chongchong ^1,2, LIU Man ^1,2

¹ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China;² Department of Medical Statistics, Jinling Hospital, Nanjing 210002, Jiangsu, China; ³Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China

Received:2019-04-19 Revised:2019-05-09 Online:2019-10-26 Published:2019-10-28

摘要/Abstract

摘要：

目的:双盲随机对照试验中，常规等比分组下的盲态分析容易实现，而对倍比分组的情形尚无有效的盲态分析方法。本文旨在实现倍比分组下双盲随机对照试验的盲态统计分析，以避免知晓分组信息后可能导致的分析偏倚。方法:在试验设计阶段，根据试验各组的整倍比数进行等样本量拆分，并按拆分后的组别进行编码随机分配和药物编盲。在统计分析阶段根据试验各组比例对拆分组的所有可能组合进行统计分析和报告。结果:结合一个两组2∶1倍比分组的临床试验实例，阐明了盲态分析的具体实现过程。本方法在进行一级揭盲后仅知晓各拆分组的编码，无法判断其对应的试验组别，因此在对各种组合进行统计分析时能保持盲态，在二级揭盲确定实际分组后可选定相应的统计分析报告。结论:本方法原理简单、实施容易、符合监管要求，尽管在随机设计、药物编盲、统计分析环节增加了工作量，但能很好实现双盲试验的盲态分析，有效避免因分析阶段破盲而导致的偏倚，对保证临床试验分析的客观性和科学性具有独到的实际应用价值。

关键词: 双盲随机对照试验, 倍比分组, 盲态分析

Abstract:

AIM: The blinded data analysis under the conventional equal ratio grouping is easy to be realized in the double-blind randomized controlled trial.However, there is no effective blinded analysis method for the trial of unequal integer ratio grouping.To develop a blinded analysis under the unequal integer ratio grouping to avoid the bias during data analysis due to knowledge of grouping information in the double-blind randomized controlled clinical trials. METHODS: In the design phase, according to the sum of unequal integer ratios, the samples were divided into several equal split groups.The random allocation sequence was generated by means of the new split groups.The drug labeling was conducted by a third party independent of the study based on the split groups.In the statistical analysis phase, all possible combinations of the split groups were analyzed and reported.RESULTS:The implementation of blind analysis was illustrated with a clinical trial in which two groups were grouped in 2∶1 ratio. In this method, only the codes of each subgroup were known after the first level unblinding, and the corresponding real group could not be identified, so it could keep blinded to treatment allocation in the statistical analysis.The final reporting of statistical analysis could be determined after the second level unblinding.CONCLUSION: The method we proposed is simple in principle, easy to implement and in line with the regulatory requirements.In spite of increasing workload during the random allocation sequence generating, drugs labeling,and statistical analysis,it could maintain the blindness of data analysis under the unequal integer ratio grouping and effectively avoid the possible analysis bias caused by unblinding.It has unique practical value in ensuring objectivity and science of clinical trial analysis.

Key words: double-blind randomized controlled trial, integer ratio grouping, blinded analysis

中图分类号:

R969.4

刘雅琦，陆梦洁，刘玉秀，陈羽，袁阳丹，周憧憧，刘曼. 倍比分组双盲随机对照试验的盲态分析[J]. 中国临床药理学与治疗学, 2019, 24(10): 1155-1160.

LIU Yaqi, LU Mengjie, LIU Yuxiu, CHEN Yu, YUAN Yangdan, ZHOU Chongchong, LIU Man. Blinded analysis of double-blind randomized controlled trial for unequal integer ratio grouping[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(10): 1155-1160.

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倍比分组双盲随机对照试验的盲态分析

Blinded analysis of double-blind randomized controlled trial for unequal integer ratio grouping

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