【作者】 张大铮；

【导师】 段俊国；

【作者基本信息】 成都中医药大学 ， 中西医结合临床， 2013， 博士

【摘要】 目的：基于目前中医药随机平行对照临床试验模式在评价个体疗效的局限,通过引入n-of-1设计,采用病证结合的方法进行中医药个体疗效交替对照临床试验研究,以期为探索建立中医药特色个体化疗效评价模式提供新的途径与方法。方法：试验类型：以糖尿病视网膜病变气阴两虚证型为研究疾证,采用多中心随机双盲n-of-1个体疗效交替临床试验研究设计。干预措施：试验组药物为益气养阴中药复方,对照组药物为中药模拟剂。干预方法：受试者先使用一种药物治疗4周后,经过1周的药物洗脱期,接着使用另一种药物治疗4周为1个交替配对的治疗周期,每个受试者需完成两个配对治疗周期。测量指标：单组药物治疗后收集受试者的视力、眼底、中医证候要素等疾病和证候指标。个体疗效评价方法：对视力、眼底、中医证候要素的改善情况先独立评价,后采用加权的方法进行个体疗效的综合评价。统计分析：组间差异采用meta分析Z检验以分析药物间疗效差异。伦理审查：试验需上报成都中医药大学附属医院伦理委员会,经审核同意后方可进行临床试验研究。结果：1.本次临床研究共纳入符合标准的受试者41例,完成临床试验有效病例33例。2.个体综合疗效评价中益气养阴中药复方疗效优于中药模拟剂的疗效的共计19例,中药模拟剂疗效优于益气养阴中药复方的共计11例,余下3例无法判断药效优势。3.益气养阴中药复方与中药模拟剂组间疗效经过Z检验存在统计学差异(Z=2.04，P=0.04<0.05),说明对于糖尿病视网膜病变气阴两虚证型个体治疗上益气养阴中药复方优于中药模拟剂的可能性较高。结论：n-of-1研究设计相比随机平行对照RCT疗效评价模式,基线控制要求较低,受试者依从度较好,评价效能较高,更接近对真实世界的模拟,适合运用在基本证型稳定的慢性病中医药个体化疗效评价中。该模式的优化升级可以在临床评价中进一步体现中医“辩证论治”的动态化特色,从而为建立个体化、动态化的中医药临床疗效评价模式提供一种新的途径与方法理论更多还原

【Abstract】 Object:For the limit of the parallel randomized controlled clinical trial mode of traditional Chinese medicine in evaluating the individual effect, we use the experimental design of ’n-of-one’ to operate a cross controlled clinical trial to assess the effect of Traditional of Chinese Medicine, to provide a new approaches and methods in exploring clinical effect evaluation mode for individual effect.Method:Researchobject:diabetic retinopathy with ’qi and yin deficiency’.Research type:multi-center random double blind and the mode of ’n-of-one’. Intervention:The trail group patient was given chinese herbal compound to rich ’qi and yin’; the control group patient was given simulation of Chinese herbal compound. Every patient accepted two treatment cycles. One treatment cycle was operated like that one patient was given one of the two drugs for4weeks, then the next1Week was washout period, then the other drug was given for the next4weeks, the next1week was washout period.Test indicator:After one treatment cycle, indicators were recorded:Vision, retina change, TCM syndrome elements.The evaluation method for individual curative effect:firstly every indicator was evaluated respectively, then the comprehensive evaluation of curative effect on individual was evaluated.Statistical analysis:using meta-analysis Z test to analyze the difference between groups to show the efficacy differences.Ethical review:The clinical trial was approved by the ethics committee of ’the affiliated hospital of chengdu university of traditional Chinese medicine’.Results:1. In the41patients included,33patients completed the whole treatment cycle.2.19patients showed the better curative effect coming from the chinese herbal compound to rich ’qi and yin’,11patients showed the better curative effect coming from the simulation,3patients curative effect couldn’t been evaluated.3. High possibility is that chinese herbal compound to rich ’qi and yin’ is better than the simulation based on the statistical data (Z=2.04, P=0.04<0.05).Conclusion:The evaluate mode of ’bing-zheng combination of TCM’ based on ’n-of-one’ could reflects the individual efficacy evaluation in traditional Chinese medicine, which shows the ’bian zheng lun zhi’. Optimized research mode of ’n-of-one’ is a new approaches and methods for evaluating individual effect.更多还原