中药新药临床试验方案设计常见问题分析
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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。
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.
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。
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.
引文
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[6]向楠,邓阿黎,邓兰琼,翟华强,李晓东.中药新药临床试验对照药选择的问题与对策.中国临床药理学与治疗学.2005,10(5):598-600.
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[9]李涛.中药新药临床试验中影响创新性评价的几个问题.药品技术审评论坛专刊,2006,4:65-69.
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[11]关德祺,梁秉中,郑景辉,丁安伟.中药临床试验研究使用的安慰剂的系统评价.南京中医药大学学报,2006,22(3):183-185.
[12]张宏伟,刘建平.临床试验中的盲法.中医杂志,2007,48(5):408-411.
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[14]李慧,梁伟雄.新药临床试验盲法对照中可能存在的偏倚.中药新药与临床药理,2005,16(5):391-392.
[15]熊宁宁,罗玫,蒋萌,刘芳,邹建东,符为民.中药临床试验的适应证侯设计与 疗效评价.中国临床药理学与治疗学,2003,8(6)715-717.
[16]李涛.证候评估早中药新药临床试验中的地位.药品技术审评论坛专刊,2006,4:62-64.
[17]吴崇胜,陈家旭,胡立胜.Delphi法建立中医证候诊断标准中权重系数确定法新探——双百分法.中国中医基础医学杂志,2006,12(4):254-255.
[18]张君,李国信,张锡玮.谈新药临床试验中受试者和研究者依从性问题.辽宁中医杂志,2005,32(8)854-855.
[19]KIDDKE,ALT MANDG.Adherence in social context[J].Control Clin rial,2000,21(5 Suppl):184.
[20]李攻戍.中药新药临床安全性评价.中药新药与临床药理,2005,16(1)3-5.
[1]李涛.证候评估在中药新药临床试验中的地位.药品技术审评论坛专刊,2006,14(4):62-64.
[2]吴敦序.中医基础理论.上海科学技术出版社,1995,7.
[3]赖世隆.中风病疗效评价指标体系的初步研究.中国中西医结合杂志.2004,74(3)709-714.
[4]杜宝俊.中药新药临床研究方案设计中相关问题探讨.中国临床药理学与治疗学,2005,10(9):1073-1075.
[5]刘建平.中医药临床试验的对照与盲法设置.中国中西医结合杂志.2003,(23)10:789-790.
[6]寿小云.中药临床试验的对照观察与试验设计.中药新药与临床药理.2001,(12)1:55-60.
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[12]关德祺,梁秉中,郑景辉,丁安伟.中药临床试验研究使用的安慰剂的系统评价.南京中医药大学学报2006,22(3):183-185.
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[2]中医现代化科技发展战略研究课题组.中医疗效系统评价体系的研究.世界科学技术——中医现代化,2002,4(2):12-14.
[3]张宗仁,黄传贵,彭明秀.新药研究中的问题与对策.中国民族民间医药杂志,1994,11:8-11.
[4]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002.6-7.
[5]张瑞明,李延谦.中药新药Ⅱ、Ⅲ期临床研究有关问题的探讨[J].中药新药与临床药理,2004,15:66-67.
[6]向楠,邓阿黎,邓兰琼,翟华强,李晓东.中药新药临床试验对照药选择的问题与对策.中国临床药理学与治疗学.2005,10(5):598-600.
[7]张宏伟,唐金陵,刘建平.临床试验中的对照设置[J].中医杂志,2007,48(2):125-128.
[8]刘建平.中医药临床试验的对照与盲法设置.中国中西医结合杂志,2003,(23)10:789-790.
[9]李涛.中药新药临床试验中影响创新性评价的几个问题.药品技术审评论坛专刊,2006,4:65-69.
[10]杜宝俊.中药新药临床研究方案设计中相关问题探讨.中国临床药理学与治疗学,2005,10(9):1073-1075.
[11]关德祺,梁秉中,郑景辉,丁安伟.中药临床试验研究使用的安慰剂的系统评价.南京中医药大学学报,2006,22(3):183-185.
[12]张宏伟,刘建平.临床试验中的盲法.中医杂志,2007,48(5):408-411.
[13]徐天和,王玖.随机化原则与盲法原则.2005,40(8):502-503.
[14]李慧,梁伟雄.新药临床试验盲法对照中可能存在的偏倚.中药新药与临床药理,2005,16(5):391-392.
[15]熊宁宁,罗玫,蒋萌,刘芳,邹建东,符为民.中药临床试验的适应证侯设计与 疗效评价.中国临床药理学与治疗学,2003,8(6)715-717.
[16]李涛.证候评估早中药新药临床试验中的地位.药品技术审评论坛专刊,2006,4:62-64.
[17]吴崇胜,陈家旭,胡立胜.Delphi法建立中医证候诊断标准中权重系数确定法新探——双百分法.中国中医基础医学杂志,2006,12(4):254-255.
[18]张君,李国信,张锡玮.谈新药临床试验中受试者和研究者依从性问题.辽宁中医杂志,2005,32(8)854-855.
[19]KIDDKE,ALT MANDG.Adherence in social context[J].Control Clin rial,2000,21(5 Suppl):184.
[20]李攻戍.中药新药临床安全性评价.中药新药与临床药理,2005,16(1)3-5.
[1]李涛.证候评估在中药新药临床试验中的地位.药品技术审评论坛专刊,2006,14(4):62-64.
[2]吴敦序.中医基础理论.上海科学技术出版社,1995,7.
[3]赖世隆.中风病疗效评价指标体系的初步研究.中国中西医结合杂志.2004,74(3)709-714.
[4]杜宝俊.中药新药临床研究方案设计中相关问题探讨.中国临床药理学与治疗学,2005,10(9):1073-1075.
[5]刘建平.中医药临床试验的对照与盲法设置.中国中西医结合杂志.2003,(23)10:789-790.
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