提高中草药随机对照试验的质量Ⅱ:对照组设计

目的:如何选择对照组是临床随机对照试验设计的关键环节之一。通过对Cochrane图书馆发表的关于中草药治疗2型糖尿病系统评价中所包含的66个临床试验进行对照组设计的评价分析,探讨如何提高中草药临床试验中对照组设计的质量。方法:文献检索2005年7月前发表于Cochrane图书馆且纳入临床试验最多的系统评价——中草药治疗2型糖尿病系统评价中的66个临床试验,分析中草药临床随机对照试验在对照组设计方面存在的问题。结果:在66个临床试验中,所采用的对照组包括安慰剂组、阳性药物组及空白对照组等,但在临床试验设计中则并未说明对照组的选择理由;其中27个临床试验采用中、西药结合与西药疗效的比较;24个临床试验采用中药与西药疗效的比较;5个临床试验采用中药与安慰剂疗效的比较;3个临床试验比较了中、西药结合与西药合安慰剂治疗的疗效;3个临床试验比较了中、西药结合与其他中药治疗的疗效;中药治疗组与空白对照组比较、中药合安慰剂治疗与西药合安慰剂治疗的比较则各为1个临床试验;另有1个临床试验采用了中药分别与中、西药结合,西药以及安慰剂的比较;有1个试验则采用了中药分别与西药及中、西药结合的比较。结论:基于不同的临床试验目的选择对照组是进行对照组设计的根本依据。建议:(1)研究者与设计者必须正确理解对照组选择的重要意义;(2)对照组的选择必须以试验设计目的为基础;(3)选择阳性药物对照组必须有充足的证据证明该阳性药物的疗效,同时必须遵照推荐方法使用阳性药物;(4)必须确保安慰剂所含成分为惰性成分,对所研究疾病无任何治疗作用,且在色、泽、味、形等方面尽可能与试验药物一致;(5)空白对照组的选择必须充分考虑伦理道德因素,且不会因为非盲法评估而对结局评估产生任何偏倚;(6)在对慢性、稳定性疾病进行的研究中,交叉对照试验常较随机对照试验更为适宜。

Improving the quality of randomized controlled trials in Chinese herbal medicine, part Ⅱ: control group design

Objective: To discuss the types of control groups in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the design of control group in future clinical studies in this therapeutic area. Methods: A search of the Cochrane Library was conducted in July 2005 to identify RCTs of CHM, and 66 RCTs with CHM for type 2 diabetes mellitus were obtained as the basis for further analysis. Results: Of 66 RCTs with CHM for type 2 diabetes mellitus, 61 (92.4%) trials had both a treatment group and a control group. Twenty-seven (40.9%) RCTs compared CHM plus conventional drug vs conventional drug, 24 (36.4%) compared CHM vs conventional drug, 5 (7.6%) compared CHM vs placebo, 3 (4.5%) compared CHM plus conventional drug vs conventional drug plus placebo, 3 (4.5%) compared CHM plus conventional drug vs other CHM, 1 (1.5%) compared CHM vs no treatment, 1 (1.5%) compared CHM plus placebo vs conventional drug plus placebo, 1 (1.5%) compared CHM vs CHM plus conventional drug vs conventional drug vs placebo, and 1 (1.5%) compared CHM vs conventional drug vs CHM plus conventional drug. Conclusion: A variety of control groups were used in RCTs of CHM for type 2 diabetes mellitus, including placebo, active, and no treatment control groups. Justification for selecting particular types of control groups were not provided in the trials reviewed in this study. Different control groups may be appropriate according to the study objectives, and several factors should be considered prior to selecting control groups in future RCTs of CHM. Recommendations: (1) Investigators of CHM who design clinical trials should understand the rationale for selecting different types of control groups; (2) Control groups for RCTs should be selected according to study objectives; (3) Active control groups should select interventions for comparisons that have the strongest evidence of efficacy and prescribe them as recommended; (4) Placebo control groups should select a placebo that mimics the physical characteristics of test intervention as closely as possible and is completely inert; (5) No treatment control groups should only be used when withholding treatment is ethical and objectives outcomes will not be subject to bias due to absent blinding; (6) Crossover control groups may be appropriate in chronic and stable conditions.