DPP-4抑制劑治療2型糖尿病臨床試驗方案設計與2型糖尿病臨床試驗問題分析
發(fā)布時間：2019-01-10 16:48
【摘要】：背景和目的:糖尿病廣泛存在于世界各地,中國居全球首位,其中95%為2型糖尿病(T2DM)。在所有抗高血糖藥物中,二肽基肽酶-4(DPP-4)抑制劑發(fā)展迅速并取得巨大成功,DPP-4抑制劑臨床試驗也進入蓬勃發(fā)展階段。從以往的研究文獻和藥品審評中心(CDE)登記注冊的T2DM臨床試驗記錄中發(fā)現(xiàn),試驗周期太短、終點指標描述不明確,受試者入選標準和排除標準設置過于簡單,這對試驗過程中實施及之后的生產(chǎn)申報留下了隱患。本文將對DPP-4抑制劑治療T2DM臨床試驗的設計進行系統(tǒng)性研究,希望對以后相關的試驗的設計提供參考。藥物臨床試驗的質(zhì)量,直接關系到試驗的準確性與真實性和人的生命健康與安全。藥物臨床試驗是一個持續(xù)性的繁瑣過程,期間會出現(xiàn)各種影響試驗質(zhì)量的問題。本文對T2DM臨床試驗項目開展過程中的具體問題進行歸納分析,探討出現(xiàn)這些主要問題的可能原因,提出合理的對策和建議,為今后提高相關試驗的質(zhì)量提供參考。方法:對88篇DPP-4抑制劑隨機對照臨床試驗(RCT)的文獻的受試者選擇和終點指標進行頻數(shù)統(tǒng)計,分析總結(jié)受試者選擇和終點指標選擇的原則。對文獻報道的AE進行統(tǒng)計,分析DPP-4抑制劑臨床試驗AE的情況。對5個T2DM臨床試驗的監(jiān)查報告、稽查報告,系統(tǒng)抽查QC和答疑表的數(shù)據(jù)進行計量統(tǒng)計,分析T2DM臨床試驗過程中的易發(fā)問題。結(jié)果:受試者選擇:入選標準中都會對年齡為18(20)-80y、確診為T2DM、BMI為20-40(少于40)且3個月內(nèi)體重穩(wěn)定(幅度不超過10%)和糖化血紅蛋白(Hb A1c)范圍(下限為6.5%-8%,上限為8.0%-12%)有規(guī)定。目前正在使用的非禁止用藥必須達到穩(wěn)定劑量,飲食和運動穩(wěn)定。排除標準中包括胰腺疾病(手術),有DM并發(fā)癥,肝腎功能不全,嚴重心腦血管疾病和其他嚴重疾病影響療效和安全評價的,使用違禁用藥,減肥。終點指標:Hb A1c相比基線的變化作為主要終點指標,選擇次要終點指標時,體重、空腹血糖(FPG)的變化,Hb A1c≤6.5%(和/或7.0%)都是可取的,安全性終點是每一個試驗統(tǒng)計分析都應考慮的點。AE:DPP-4抑制劑臨床試驗主要發(fā)生AE有頭痛、上呼吸道感染、尿路感染、鼻咽炎、背痛、流感、低血糖、高血壓、胃腸道相關AE(發(fā)生率≥4%)。T2DM臨床試驗過程中易發(fā)問題:監(jiān)查、稽查和系統(tǒng)抽查QC發(fā)現(xiàn)最常見的問題是研究病歷/CRF的問題,答疑表中發(fā)現(xiàn)最常見的問題是化驗值未有判斷或者判斷有誤。結(jié)論:總結(jié)DPP-4抑制劑臨床試驗方案設計的原則,并撰寫試驗方案。優(yōu)秀的監(jiān)察員、科學合理的監(jiān)查,引入專職臨床協(xié)調(diào)員,運用電子數(shù)據(jù)采集系統(tǒng)和中央隨機系統(tǒng)能大大減少T2DM臨床試驗中問題的發(fā)生,提高試驗質(zhì)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，
本文編號：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，
本文編號：2406552
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