中医药治疗功能性消化不良临床试验中的中药安慰剂效应Meta分析

Meta-Analysis of the Placebo Effect of Chinese Herbal Medicine in Clinical Trials of Traditional Chinese Medicine for Functional Dyspepsia

目的分析中医药治疗功能性消化不良(FD)随机对照试验(RCTs)中的中药安慰剂实施现状并系统评价其安慰剂效应。方法利用医学主题词和自由词组合检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据库收录的1994年1月31至2023年9月30日发表的设有中药安慰剂组治疗FD的RCTs,分析其剂型、成分及评价方法现状,通过Cochrane偏倚风险评估标准评价文献质量,对FD患者的中药安慰剂应答率进行单组率Meta分析,并根据诊断标准、疗效标准、治疗时间、安慰剂剂型、是否含有活性成分及是否行安慰剂评估进行亚组分析和Meta回归分析。结果纳入34篇文献,共5046例患者,其中2221例FD患者接受了中药安慰剂治疗。颗粒剂为最主要的安慰剂剂型,占71%(24/34),32.35%(11/34)研究的安慰剂添加了原药,只有12项(35%)研究对外观、气味、味道都进行了描述。安慰剂组FD患者安慰剂应答率为41%(95%CI:0.35~0.47;P<0.01,I^(2)=87%);不同诊断标准、不同治疗时间的组间差异有统计学意义(P<0.05),但不同疗效评价标准、不同安慰剂剂型、是否含有低剂量活性成分、是否进行安慰剂评估的组间差异无统计学意义(P>0.05)。结论FD患者存在明显的中药安慰剂效应,颗粒剂为主要的安慰剂剂型,不同诊断标准、不同治疗时间可能会影响患者的应答率,中药安慰剂中加入低剂量原药未见对应答率具有影响。临床试验者对安慰剂的关注度还不够,中药安慰剂的制作和评价缺乏统一的标准和规范性。

Objective To analyse the current implementation status of Chinese herbal medicine(CHM)placebo and systematically evaluate the placebo effect in randomised controlled trials(RCTs)of traditional Chinese medicine(TCM)for the treatment of functional dyspepsia(FD).Methods A combination of medical subject terms and free words was used to search six databases,including PubMed,EMBASE,Cochrane Library,Web of Science,China National Knowledge Infrastructure,and Wanfang,for RCTs with CHM placebo group for FD published from January 31st,1994 to September 30th,2023.The dosage forms,composition,and methodological quality were collected and evaluated.The quality of the included articles was evaluated by Cochrane risk of bias assessment tool,and meta-analysis was performed on the CHM placebo response rate of patients with FD,and subgroup analysis and meta-regression was performed according to diagnostic criteria,efficacy criteria,duration of treatment,type of placebo,whether it contained active ingredient,and whether it evaluated placebo effects.Results A total of 34 publications were included involving 5046 participants,of which 2221 FD patients received CHM placebo treatment.Granules were the predominant placebo preparation,accounting for 71%(24/34);32.35%(11/34)of the studies added real CHM to the placebo,and only 12(35%)of the studies described appearance,odour,and taste.The placebo response rate in FD patients in the placebo group was 41%(95%CI:0.35 to 0.47;P<0.01,I^(2)=87%);there was significant difference between groups with different diagnostic criteria and different treatment durations(P<0.05 or P<0.01),but there was no significant difference between the different efficacy evaluation criteria,the different placebo preparation,the presence of a low-dose active ingredient,and the presence or absence of placebo assessment(P>0.05).Conclusion There was a significant CHM placebo effect in patients with FD,with granules as the main preparation of placebop.Different diagnostic criteria and different treatment times may affect the response rate of patients,and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate.Clinical investigators have not paid enough attention to placebos,and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.