中药新药临床试验方案设计常见问题分析

【作者】 谢志敏；

【导师】 杜宝俊；

【作者基本信息】 中国中医科学院 ， 中医内科学， 2009， 硕士

【摘要】 临床试验设计是药物研究的重要环节,严谨、科学基础上的临床试验设计,是科学、客观评价中药新药临床疗效的基础。《药品临床试验管理规范》(GCP)和《中药新药临床研究指导原则》的颁布施行,临床流行病学/DME方法在中医药疗效评价的引入,对于中药新药临床试验循着科学化、规范化方向发展起到积极的推动作用。但是,在中药新药的试验设计中还存在诸多不合理问题,影响了疗效的评价。本文就中药新药临床试验设计中普遍存在的技术问题进行讨论。目的:通过分析试验设计中存在的诸多影响疗效评价的问题,并提出了修改意见,以期使临床试验方案设计更符合中医药治疗疾病的特色,更能够体现中医药的治疗优势,以提高临床试验质量。方法:综述中药新药临床试验设计的近年文献,小结存在的常见问题,结合中药新药临床试验设计中的经验,对试验设计的相关问题进行分析,并提出解决对策。最后选择具有代表性(能体现中医药治疗特色和优势的功能性疾病)的中药新药临床研究方案,评析“复方补肾颗粒治疗功能性勃起功能障碍临床试验方案”设计中出现的各类问题,并尝试提出修改建议,完善临床试验设计,以提高中医药临床疗效评价的质量。结果:第一部分通过文献整理,对近年来中药新药临床设计中常见的问题进行综述,发现存在诸如对证候确立不合理、对照药选择不当、盲法实施欠严谨、证候量化随意性大及依从性和安全性问题。第二部分是在文献综述的基础上,结合中药新药临床试验设计中遇到的问题进行整理小总结,就病证结合模式和证候模式的选择问题、治疗过程中证候变化的处理问题、证候的规范化问题、合理选择对照药的问题和合并用药问题等诸多影响临床疗效评价的较关键性问题进行剖析,并提出解决对策。第三部分结合功能性勃起功能障碍的具体实例进行分析,对“复方补肾颗粒治疗功能性勃起功能障碍临床试验方案”在试验设计中存在的诊断、辨证问题、证候变化问题及合并用药和疗效指标等诸多问题提出了修改意见。结论:通过对临床试验中证候确立不合理、对照药选择不当、盲法实施欠严谨、证候的规范化问题、病证结合模式问题、依从性问题、安全性问题、合并用药不详细、疗效判定指标不全面和未处理试验中的证候变化等问题的合理处理,可使临床试验方案设计更符合中医药治疗疾病的特色,更能够体现中医药的治疗优势。更多还原

【Abstract】 Clinical trial design is an important part of pharmaceutical researches.The scientific and objective evaluation of efficacy of Chinese medicine is based on the rigorous and scientific designs of clinical trials.The promulgation and implementation of Good Clinical Practice and Chinese Medicine Clinical Research Guiding Principles,and the application of clinical epidemiology in TCM Clinical Efficacy Evaluation promote the development of clinical trials of Chinese medicine.However,clinical trials of Chinese medicine have many problems,which influence evaluation of the effect of Chinese medicine.The thesis discusses some common problems in the designs of clinical trial of Chinese medicine.Objective:To embody all the advantages of traditional chinese medicine and improve the quality of clinical trial,This thesis discusses some problems in the designs of clinical trials.Methods:The thesis summarizes and analyzes problems which influence evaluation of therapeutic efficiency in the design of new drugs in clinical trials of Chinese medicine,and then proposes corresponding solutions.In the last,to embody all the advantages of traditional chinese medicine and improve the quality of clinical trial, combined with example of the clinical trial of treating psychological erectile dysfunction with Compound Kidney-Nourishing Particles,the thesis puts forward consulting opinions about problems in the clinical trial.Results:The first prat is literature review,which reviews the common problems in the design of clinical trial of Chinese medicine and discusses inaccuracy syndrome,unsuitable control medicine,no precise blind method,too much subjectivity in standards of syndrome-differentiated diagnosis,compliance and security.Based on the literature review,the second part makes a critical analysis on the problems in the designs of clinical trial of Chinese medicine,including the model choice between combination of disease and syndrome and syndrome,lack of syndrome changes treatment in therapeutic process,too much subjectivity in standards of syndrome-differentiated diagnosis,ill-chosen medicine in control group and mismanagement of drug combination,and sets forth countermeasures.To embody all the advantages of traditional chinese medicine and improve the quality of clinical trial,combined with example of the clinical trial of treating psychological erectile dysfunction with Compound Kidney-Nourishing Particles,the third part puts forward consulting opinions about problems in the clinical trial,including unreasonable differentiation of symptoms and signs,lack of syndrome changes treatment in therapeutic process,no precise blind method,mismanagement of drug combination and incomplete indexes of effect judgement.Conclusion:Handling of problems reasonably,such as inaccuracy syndrome,unsuitable control medicine,no precise blind method,too much subjectivity in standards of syndrome-differentiated diagnosis,the model choice between combination of disease and syndrome and syndrome,compliance and security,lack of syndrome changes treatment in therapeutic process and mismanagement of drug combination,can embody all the advantages of traditional chinese medicine.更多还原