基于支气管扩张症的中医药单病例随机对照试验方法学研究  

Methodological study on N-of-1 trials of traditional Chinese medicine based on bronchiectasis

作　　者：陈绘佳 黄海茵[1] 王振伟[1] 杨佩兰[1] 吴银根[3] 徐敏华[1] 张谊[1] 汤杰[1] 王明莉 陆立志 安佳琪 年华[4] 沈丽华 CHEN Huijia;HUANG Haiyin;WANG Zhenwei;YANG Peilan;WU Yingen;XU Minhua;ZHANG Yi;TANG Jie;WANG Mingli;LU Lizhi;AN Jiaqi;NIAN Hua;SHEN Lihua(Department of Respiratory Disease,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,P.R.China;Department of Traditional Chinese Medicine,Minhang Hospital,Fudan University,Shanghai 201199,P.R.China;Department of Respiratory Disease,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,P.R.China;Department of Pharmacy,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,P.R.China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院呼吸科,上海200437 [2]上海市闵行区中心医院中医科,上海201199 [3]上海中医药大学附属龙华医院呼吸科,上海200032 [4]上海中医药大学附属岳阳中西医结合医院药剂科,上海200437

出　　处：《中国循证医学杂志》2025年第3期319-328,共10页Chinese Journal of Evidence-based Medicine

基　　金：国家自然科学基金项目(编号:81874515);上海市进一步加快中医药事业发展三年行动计划中医优势病种培育建设项目(编号:ZY[2018-2020]-ZYBZ-08);上海市卫生健康委员会中医药科研项目(编号:2022QN073)。

摘　　要：目的通过一系列单病例随机对照试验,评估中医个体化辨证论治对稳定期支气管扩张症的疗效,探索一种符合中医诊疗特点的临床试验方法。方法原计划3轮次,每轮分试验、对照两个观察期。每期用药3周,停药1周。因结果不及预期,增加一轮试验(共4轮)。试验期服个体化辨证论治方,对照期服安慰剂。结局指标为总体症状Likert量表评分(主要指标)、呼吸症状Likert量表评分、CAT评分、24小时痰量、中医症候评分。数据分析(包括残留效应与阶段效应分析)采用了成组设计的独立样本t检验、配对t检验或非参数检验,混合效应模型以及贝叶斯分析。结果共纳入31例患者,完成4轮次试验的有24例患者。成组设计的独立样本t检验、混合效应模型显示试验中无阶段效应和残留效应。贝叶斯分析显示部分个体的部分结局指标上个体化方存在残留效应。6例患者在总体症状Likert量表评分上中药优于安慰剂(P<0.05);贝叶斯分析发现中药在更多的个体疗效优于安慰剂。但在群体水平,两方在各项指标比较均未见统计学差异。结论本研究方法高度模拟中医药临床实践,具有良好的可操作性和患者依从性,总体上无明显中药残留效应,可提供中医药短期疗效的最佳个体化循证医学证据。贝叶斯分析可提高个体统计的敏感性。Objective A series of N-of-1 trials were conducted to evaluate the effects of traditional Chinese medicine(TCM)individualized syndrome differentiation on stable bronchiectasis,and to explore a clinical trial method that is consistent with the characteristics of TCM.Methods The original plan consisted of 3 cycles,with each cycle consisting of two observation periods:experimental and control.Take the medication for 3 weeks each period and then stop for 1 week.Because the results were not as expected,another cycle of trials was added(a total of 4 cycles).The trial period was treated with individualized syndrome differentiation prescription and the control period was treated with placebo.The outcome measures were Likert scale score of general symptoms(primary outcome),Likert scale score of respiratory symptoms,CAT score,24h sputum volume and TCM symptom score.Data analysis(including residual effects and stage effects analysis)used group-designed independent sample t tests,paired t tests or non-parametric tests,mixed effects models,and Bayesian analysis.Results A total of 31 participants were formally enrolled,with 24 completing all four cycles.Independent sample t-tests and mixed-effects models showed no significant period or carryover effects.Bayesian analysis showed that there were residual effects on some outcome measures of some individuals.Six participants showed statistically significant differences in overall symptom Likert scale scores(P<0.05).Bayesian analysis found that TCM was more effective than placebo in more individuals.No significant differences were found between individualized TCM and placebo at the group level for any of the outcome measures.Conclusion This study method highly simulates the clinical practice of TCM,with good operability and patient compliance,and has no obvious residual effect of TCM on the whole,which can provide the best individualized evidence-based medicine evidence of short-term efficacy of TCM.Bayesian analysis can improve the sensitivity of individual statistics.

关 键 词：单病例随机对照试验 支气管扩张症 残留效应 辨证论治 中医药 

分 类 号：R47[医药卫生—护理学]