DPP-4抑制剂治疗2型糖尿病临床试验方案设计与2型糖尿病临床试验问题分析
发布时间：2019-01-10 16:48
【摘要】：背景和目的:糖尿病广泛存在于世界各地,中国居全球首位,其中95%为2型糖尿病(T2DM)。在所有抗高血糖药物中,二肽基肽酶-4(DPP-4)抑制剂发展迅速并取得巨大成功,DPP-4抑制剂临床试验也进入蓬勃发展阶段。从以往的研究文献和药品审评中心(CDE)登记注册的T2DM临床试验记录中发现,试验周期太短、终点指标描述不明确,受试者入选标准和排除标准设置过于简单,这对试验过程中实施及之后的生产申报留下了隐患。本文将对DPP-4抑制剂治疗T2DM临床试验的设计进行系统性研究,希望对以后相关的试验的设计提供参考。药物临床试验的质量,直接关系到试验的准确性与真实性和人的生命健康与安全。药物临床试验是一个持续性的繁琐过程,期间会出现各种影响试验质量的问题。本文对T2DM临床试验项目开展过程中的具体问题进行归纳分析,探讨出现这些主要问题的可能原因,提出合理的对策和建议,为今后提高相关试验的质量提供参考。方法:对88篇DPP-4抑制剂随机对照临床试验(RCT)的文献的受试者选择和终点指标进行频数统计,分析总结受试者选择和终点指标选择的原则。对文献报道的AE进行统计,分析DPP-4抑制剂临床试验AE的情况。对5个T2DM临床试验的监查报告、稽查报告,系统抽查QC和答疑表的数据进行计量统计,分析T2DM临床试验过程中的易发问题。结果:受试者选择:入选标准中都会对年龄为18(20)-80y、确诊为T2DM、BMI为20-40(少于40)且3个月内体重稳定(幅度不超过10%)和糖化血红蛋白(Hb A1c)范围(下限为6.5%-8%,上限为8.0%-12%)有规定。目前正在使用的非禁止用药必须达到稳定剂量,饮食和运动稳定。排除标准中包括胰腺疾病(手术),有DM并发症,肝肾功能不全,严重心脑血管疾病和其他严重疾病影响疗效和安全评价的,使用违禁用药,减肥。终点指标:Hb A1c相比基线的变化作为主要终点指标,选择次要终点指标时,体重、空腹血糖(FPG)的变化,Hb A1c≤6.5%(和/或7.0%)都是可取的,安全性终点是每一个试验统计分析都应考虑的点。AE:DPP-4抑制剂临床试验主要发生AE有头痛、上呼吸道感染、尿路感染、鼻咽炎、背痛、流感、低血糖、高血压、胃肠道相关AE(发生率≥4%)。T2DM临床试验过程中易发问题:监查、稽查和系统抽查QC发现最常见的问题是研究病历/CRF的问题,答疑表中发现最常见的问题是化验值未有判断或者判断有误。结论:总结DPP-4抑制剂临床试验方案设计的原则,并撰写试验方案。优秀的监察员、科学合理的监查,引入专职临床协调员,运用电子数据采集系统和中央随机系统能大大减少T2DM临床试验中问题的发生,提高试验质量。
[Abstract]:Background and objective: diabetes is widespread in the world, and China ranks first in the world, 95% of which is type 2 diabetes (T2DM). Among all antihyperglycemic drugs, dipeptidyl peptidase-4 (DPP-4) inhibitors have developed rapidly and achieved great success, and the clinical trials of DPP-4 inhibitors have entered a stage of vigorous development. From the previous research literature and the records of T2DM clinical trials registered by (CDE), we find that the trial period is too short, the description of endpoints is not clear, and the selection criteria and exclusion criteria are too simple. This has left a hidden danger for the implementation of the test process and the subsequent production declaration. This paper will systematically study the design of clinical trial of DPP-4 inhibitor therapy for T2DM, and hope to provide reference for the design of related trials in the future. The quality of drug clinical trial is directly related to the accuracy and authenticity of the trial and the health and safety of human life. The clinical trial of drugs is a continuous and tedious process, during which a variety of problems may affect the quality of the trial. In this paper, the concrete problems in the course of T2DM clinical trial project are summarized and analyzed, the possible causes of these main problems are discussed, and reasonable countermeasures and suggestions are put forward so as to provide references for improving the quality of related trials in the future. Methods: the subjects' selection and endpoint index of 88 articles of DPP-4 inhibitor randomized controlled clinical trial (RCT) were analyzed and summarized. According to the statistics of AE reported in the literature, the situation of AE in clinical trial of DPP-4 inhibitor was analyzed. The data of five T2DM clinical trials, such as inspection reports, audit reports, systematic random checks of QC and answering tables, were measured and analyzed to analyze the prone problems in the course of T2DM clinical trials. Results: subjects were selected. Age 18 (20)-80ywas diagnosed as T2DM. The BMI is 20-40 (less than 40) and the body weight is stable (not more than 10%) within 3 months. The range of Hb A1c (lower limit is 6.5 -8, the upper limit is 8.0 -12%). Non-prohibitive drugs currently in use must reach stable doses, diet and exercise stability. The exclusion criteria include pancreatic diseases (surgery), DM complications, liver and kidney dysfunction, severe cardiovascular and cerebrovascular diseases and other serious diseases affecting the efficacy and safety evaluation, use of illegal drugs, weight loss. Endpoint indicators: changes in Hb A1c compared to baseline as primary endpoint indicators, weight, (FPG) changes in fasting blood glucose, Hb A1c 鈮，
本文编号：2406552
[Abstract]:Background and objective: diabetes is widespread in the world, and China ranks first in the world, 95% of which is type 2 diabetes (T2DM). Among all antihyperglycemic drugs, dipeptidyl peptidase-4 (DPP-4) inhibitors have developed rapidly and achieved great success, and the clinical trials of DPP-4 inhibitors have entered a stage of vigorous development. From the previous research literature and the records of T2DM clinical trials registered by (CDE), we find that the trial period is too short, the description of endpoints is not clear, and the selection criteria and exclusion criteria are too simple. This has left a hidden danger for the implementation of the test process and the subsequent production declaration. This paper will systematically study the design of clinical trial of DPP-4 inhibitor therapy for T2DM, and hope to provide reference for the design of related trials in the future. The quality of drug clinical trial is directly related to the accuracy and authenticity of the trial and the health and safety of human life. The clinical trial of drugs is a continuous and tedious process, during which a variety of problems may affect the quality of the trial. In this paper, the concrete problems in the course of T2DM clinical trial project are summarized and analyzed, the possible causes of these main problems are discussed, and reasonable countermeasures and suggestions are put forward so as to provide references for improving the quality of related trials in the future. Methods: the subjects' selection and endpoint index of 88 articles of DPP-4 inhibitor randomized controlled clinical trial (RCT) were analyzed and summarized. According to the statistics of AE reported in the literature, the situation of AE in clinical trial of DPP-4 inhibitor was analyzed. The data of five T2DM clinical trials, such as inspection reports, audit reports, systematic random checks of QC and answering tables, were measured and analyzed to analyze the prone problems in the course of T2DM clinical trials. Results: subjects were selected. Age 18 (20)-80ywas diagnosed as T2DM. The BMI is 20-40 (less than 40) and the body weight is stable (not more than 10%) within 3 months. The range of Hb A1c (lower limit is 6.5 -8, the upper limit is 8.0 -12%). Non-prohibitive drugs currently in use must reach stable doses, diet and exercise stability. The exclusion criteria include pancreatic diseases (surgery), DM complications, liver and kidney dysfunction, severe cardiovascular and cerebrovascular diseases and other serious diseases affecting the efficacy and safety evaluation, use of illegal drugs, weight loss. Endpoint indicators: changes in Hb A1c compared to baseline as primary endpoint indicators, weight, (FPG) changes in fasting blood glucose, Hb A1c 鈮，
本文编号：2406552
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