药物临床试验受试者知情同意存在的问题及对策

药物临床试验在国内开展日渐广泛,但受试者权益保护却未能引起足够重视。本文分析了知情同意书设计、知情同意实施过程及签署中存在的不足,通过加强GCP法规培训、营造沟通氛围、提高质量控制等途径最大程度保障受试者的权益。     

沟通:知情同意的重要过程

在国人对临床试验认识不足的背景下,在当今医患关系空前紧张的形势下,作为研究者,在开展临床试验过程中如何与受试者更好地沟通并获得他们的知情同意就显得格外重要。     

我国临床研究受试者知情同意现状及改善措施

目的:了解我国临床研究受试者的知情同意现状,并提出相应的改善措施。方法:通过分析我国临床研究受试者的知情同意现状,指出其不足,并提出相应的改善措施。结果与结论:我国临床研究受试者的知情同意在立法、受试者认知、研究者执行、知情同意书及伦理审查中仍存在问题。具体体现在临床研究的立法较薄弱;受试者对临床研究存在错误认知;研究者对知情同意的认识误区,执行知情同意时出现行为失范和告知不充分的现象;知情同意书暂无统一标准;伦理委员会的审查力度不强等。建议构建完善的法律法规制度,加强对受试者的健康教育,加强研究者的培训教育,规范知情同意书,加强伦理委员会的能力建设,以改善知情同意现状。     

人体药物临床试验受试者知情同意权保护法律问题研究

目的为人体药物临床试验受试者知情同意权利的保护提供完善的对策与建议。方法通过结合现行相关规定与司法实践中的案例,分析实践中存在的问题。结果目前,我国人体药物临床试验受试者知情同意权的保护仍存在诸多问题,如知情同意告知对象的规定与实践操作不统一、受试者对药物试验信息的理解不准确等。结论应尽快修订相关法律法规,切实履行知情同意的告知义务、内容,保障受试者的意思表示真实有效,落实伦理审查等多方面来保护受试者的知情同意权利。     

生物等效性试验健康受试者筛选流程的优化

目的 探讨如何提高生物等效性试验健康受试者筛选期的工作效率.方法 试验甲给予受试者根据各个检查项目等待人数自由分流的筛选方法;试验乙给予对部分检查项目进行先后顺序限定,并要求研究者在发现受试者某项检查结果异常后,应及时终止其继续参加其他检查的筛选方法.比较2个试验中受试者在某项检查不合格时合并有其他项目检查的情况.结果...     

远程多媒体电子知情同意的知晓率和满意度模拟调研

目的 在电子知情同意模式广泛使用和新型冠状病毒影响药物临床试验的背景下,评估远程多媒体电子知情同意模式与传统知情同意模式的应用效果。方法 进行1项涉及到近6个月内消化内科的就诊患者的随机对照试验。受试者被随机分配到2种知情同意模式中的一种。干预组的受试者将通过远程电子知情同意小程序完成知情同意,对照组的受试者在医师的当面告知下完成知情同意。本试验的研究成果是2组调查对象的知情知晓率和满意度的调查问卷结果。结果 101名受试者被招募参加本次研究(干预组,n=51;对照组,n=50)。与对照组相比,干预组的受试者表现出较高的满意度,但不存在显著的统计学差异;干预组的受试者表现出更好的知情知晓率(知晓率中位数,干预组50.00% vs对照组37.50%),并观察到显著差异(P<0.001)。通过对年龄(≥50岁,<50岁)、性别和学历(本科及以上、专科、高中及以下)进行分层分析,干预组低学历(专科及以下)、中老年和女性群体的知情知晓率远高于对照组,且差异有统计学意义。结论 本次研究证实了远程电子知情同意模式的可行性和提高受试者知情知晓度的应用效果。电子知情同意可以提供更便利的知情同意方式,并节省受试者参与临床试验的成本。为了满足更多目标人群的需求,未来对电子知情同意的优化和研究是有价值的。     

对药物临床试验伦理审查中的知情同意的概述

1知情同意的定义所谓知情同意,是指人体试验受试者享有知情同意权,研究者必须取得受试者知情同意才可开展试验,即试验者必须真实充分地向受试者说明有关人体试验的情况,如果受试者本人不能行使知情同意权,则必须取得与受试者没有利益     

中医诊疗中患者知情同意的研究

患者知情同意作为一项伦理原则和权利,已被国内外学者所普遍接受,并在法律上得到体现,但现有对知情同意的研究多是针对在临床占有绝对优势地位的西医而进行。中医作为中国的传统医学,具有其自身的特色与优势,与西医从理论到临床上均存在巨大差距,本文拟对中医国内外知情同意的研究现状进行文献综述研究。     

药物临床试验电子知情同意及受试者补助电子发放的实施探索

目的:探索及评价电子知情同意(electronic informed consent)和受试者补助电子发放(electronic payment of subject compensation,简称2E)在新药临床试验中的应用情况.方法:在2项新药临床试验中应用2E技术.实施电子知情同意流程如下:在电脑端添加临床试验信...     

江苏省首例药物临床试验诉讼与受试者的知情同意权保护

《赫尔辛基宣言》前言指出：“在人体医学研究中，对受试者健康的考虑应优先于科学和社会的兴趣。”药物临床试验中，受试者的生命、健康和人格尊严，不因其参与试验而受到剥夺；相反，因为其对科学技术和人类健康的特殊贡献，更应当受到法律的严格保护。在受试者权利保护中，最基础、最核心的就是知情同意权。本研究以江苏省首例临床试验诉讼为例，分析我国药物临床试验中受试者权益保护的关键问题。     

Comparative bioequivalence study of leflunomide tablets in Indian healthy volunteers

The pharmacokinetics of teriflunomide [CAS No. 163451-81-8], the metabolite of leflunomide [CAS No. 75706-12-6] has been evaluated in adult human volunteers after oral administration of tablet formulation. However, no published data is available regarding the bioavailability of this in the Indian population. In light of the above, a study was designed to carry out a bioequivalence study of 2 preparations of leflunomide 20 mg in healthy Indian male volunteers.24 healthy male volunteers (age, 25±4.1 years; weight, 57.58±7.01 kg) were enrolled in this study. Each subject received a test and reference formulation in a single dose, fasting 2 period, 2 way crossover study with a wash out period of 4 weeks. Analysis of teriflunomide from plasma samples was done by a simple and sensitive HPLC method using UV detection developed in our laboratory. An analysis of variance was performed on the pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞ using GLM procedures in which sources of variation were subject, formulation, and period.The results indicated that there are no statistically significant differences between the 2 products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters. 90% confidence limits for the log transformed data of Cmax, AUC0-t, AUC0-∞. were within the acceptable range of 0.80-1.25.The results indicate that the 2 products are bioequivalent in terms of rate and extent of drug absorption. Both the preparations were well tolerated with no adverse reactions throughout the study.     

头孢克肟片人体药代动力学和生物等效性研究

目的研究头孢克肟供试制剂和参比制剂的药代动力学和人体生物等效性。方法用HPLC法测定18名健康受试者随机交叉口服200mg头孢克肟后血药浓度,用3P97进行最佳模型拟合,并计算药代动力学参数。结果不同时间药物在血清中的浓度符合2室模型,计算所得的供试制剂和参比制剂之间的主要药代动力学参数如下:Cmax为2.56±0.69,2.32±0.63 mg·L-1;tmax为3.17±0.66,3.5±0.62h,;tl/2β为3.15±0.49,3.31±0.51 h;AUC0-∞为19.91±5.18,19.09±5.36 mg·h.L-1;供试制剂对参比制剂的生物利用度为(106.22±1 8.48)％。结论供试制剂和参比制剂具有生物等效性。     

Clarithromycin bioequivalence study of two oral formulations in healthy human volunteers

OBJECTIVE: To assess the bioequivalence of two tablet formulations of clarithromycin (Clamicin 500 mg from Medley Indlistria Farmaceutica, Brazil, as the test formulation, and Biaxin 500 mg from Abbott Industries, USA, as the reference formulation). METHODS: A single 500 mg oral dose of each formulation was administrated in 24 healthy volunteers of both sexes (12 males and 12 females). The study was conducted open, randomized, two-period crossover design with a 7-day interval between doses. The plasma concentrations of clarithromycin were quantified by reversed phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM) method. 14-hydroxyclarithromycin concentration was estimated semiquantitatively as equivalent of clarithromycin/ml. The precision of the method was evaluated using calibration curves and plasma quality control samples. The pharmacokinetic parameters calculated for both compounds included: AUC(0 - 48h), AUC(0 - infinity), Cmax, Cmax/AUC(0 - 48h), Tmax, T1/2 and Ke. RESULTS: Standard curves of clarithromycin in plasma were linear in the range of 0.05 microg x ml(-1) to 10 microg x ml(-1) (r > 0.999). The limit of quantification was 5 ng/ml. Within- and between-run plasma quality control CV were 5.8% and 15.7%, respectively. Inaccuracy within- and between-runs were 14% and 17%, respectively. 90% CI for clarithromycin geometric mean AUC(0 - 48h), AUC(0 - infinity) and Cmax ratios (test/reference) were: 8.7% - 103.1%, 89.4% - 103.7% and 85.4% - 99.6%, respectively, and for hydroxyclarithomycin were 80.3% - 108.6%, 80.1% - 110.1% and 85.4% - 112.6%, respectively. CONCLUSION: The method described for the quantification of charithomycin and its main metabolite is accurate and sensitive. Clamicin was considered bio-equivalent to Biaxin based on the rate and extent of absorption. Since these were no significant differences in the bioequivalence determined using the pharmacokinetic parameters of either clarithromycin or 14-hydroxyclarithromycin, we suggest that future bioequivalence trials of this drug may be performed by quantifying clarithromycin only.     

格列齐特片在健康人体内的药代动力学及生物等效性研究

目的研究格列齐特片在健康人体内的相对生物利用度和生物等效性。方法20名健康成年男性志愿者采用随机分组自身交叉对照试验设计,单剂量口服80mg格列齐特片后,用高效液相色谱法测定血浆中药物浓度。结果格列齐特在0.104～12.48μg/ml浓度范围内线性良好(r=0.99988),平均回收率90.125%～104.6%,日内和日间精密度(RSD)均<10.0%。试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax):(4.4±0.9)和(4.0±0.9)h;峰浓度(Cmax):(4.8±0.6)和(5.3±0.8)μg/ml;曲线下面积(AUC)0￣48h:(86±29)和(88±33)mg·L-1·h-1;AUC0￣∞:(99±45)和(103±58)mg·L-·1h-1;消除半衰期(T1/2):(13±4)和(14±5)h。以AUC0￣48h计算的受试制剂的相对生物利用度为(99±9)%。结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效。     

Pharmacokinetic and bioequivalence study of etoricoxib tablet in healthy Bangladeshi volunteers

The aim of this study was to compare the pharmacokinetic properties of two etoricoxib (CAS 202409-33-4) 60 mg formulations, namely Etocox-60 (test product) and reference product, and to evaluate whether these two formulations meet the FDA criteria to assume bioequivalence. Twenty-four healthy volunteers were enrolled into this randomized, single-dose, 2-way crossover, open-label pharmacokinetic study. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa as a single dose of 60 mg tablets after 12 h overnight fasting, with a washout period of two weeks. Following oral administration, blood samples were collected at 0 (baseline), 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0, and 120.0 h. Serum concentration of etoricoxib was assessed using a high performance liquid chromatographic-UV spectrometry procedure. The pharmacokinetic parameters were determined by the non-compartmental method. After administering a single dose of 60 mg of each etoricoxib formulation, the obtained mean (SD) values for the test and reference products were 1.26 (0.33) and 1.29 (0.35) microg/ml for Cmax; 3.25 (2.64) and 2.63 (1.40) h for t(max); 29.63 (8.31) and 30.40 (5.85) h x microg/ml for AUC0-120; and 31.84 (10.97) and 33.00 (8.10) h x microg/ml for AUC0-infinity, respectively. The mean t1/2 was found 27.99 (7.87) h and 29.84 (7.93) h for test and reference product respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. After analysis of variance, no period, sequence or formulation effects were observed for any pharmacokinetic property. The 90% confidence intervals of the test/reference mean ratios of the 1n-transformed AUC0-120, AUC0-infinity and Cmax mean values were 95.90% (85.37%-107.74 %), 94.69% (84.43%-106.20%) and 97.87% (85.54 %-111.98 %), respectively, which fell within the predetermined FDA bioequivalence range of 80%-125%. This single-dose study found that the test and reference formulations of etoricoxib met the regulatory criteria for bioequivalence in terms of both rate and extent of absorption.     

健康人体内替硝唑片的药代动力学及生物等效性研究

目的研究替硝唑片在健康人体内的相对生物利用度和生物等效性。方法20名健康成年男性志愿者采用随机分组自身交叉试验设计,单剂量口服1.0g替硝唑片后,用高效液相色谱法测定血浆中药物浓度。结果替硝唑在0.208～41.6μg/ml浓度范围内线性良好(r=0.99975),平均回收率98.6%～99.6%,日内和日间标准误(sx)均<10.0%。替硝唑试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax)(:1.5±0.8)和(1.5±1.3)h;峰浓度(Cmax):(20±3)和(21±3)μg/ml;曲线下面积(AUC)0￣60h:(390±55)和(391±48)mg·L-1·h;AUC0￣∞:(427±79)和(424±59)mg·L-1·h;T1/2:(16.6±2.8)和(16.1±1.9)h,以AUC0￣60h计算的受体制剂的相对生物利用度为(100±6)%。结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效。     

国产苯磺酸氨氯地平片健康人生物等效性研究

目的:以进口制剂为对照,评价国产苯磺酸氨氯地平片生物等效性.方法:采用2制剂双周期自身对照试验设计.18名男性健康志愿者随机分别服用单剂量苯磺酸氨氯地平试验片剂和参比片剂10mg,采用LC/MS/MS法检测,测定血浆苯磺酸氨氯地平的浓度.采用DAS 2.0程序计算药动学参数.结果:苯磺酸氨氯地平血药浓度在0.050～20.0μg·L-1范围内线性关系良好(r=0.994 9),最低定量浓度为0.050μg·L-1,日内及日间精密度RSD＜7.4%.参比制剂和试验制剂苯磺酸氨氯地平的AUC0～tn分别为(249.4 ±68.6)和(251.9±53.4)μg·h·L-1,AUC0～∞分别为(287.9-6 84.0)和(288.2.±67.5)μg·h·L-1;Cmax分别为(6.02 ±1.45)和(6.39±1.71)μg·L-1;Tmax分别为(7.90±2.94)和(8.00 ±3.40)h.以AUC0～tn与AUC00～∞计算相对生物利用度分别为(104.7 ±25.2)%和(103.5±25.7)%.结论:建立的分析方法准确灵敏,2种制剂生物等效.     

氟康唑在健康人体的药物动力学和生物等效性

目的 研究氟康唑(抗真菌药)在健康人体的药物动力学及生物等效性.方法 20名健康志愿者随机双交叉、单剂量口服受试制剂和参比制剂150 mg,用高效液相色谱-串联质谱联法测定人血浆中氟康唑的浓度.使用DAS软件拟合计算药物动力学参数和相对生物利用度,评价两制剂的生物等效性.结果 受试制剂和参比制剂药物动力学参数:Cmax分别为(3.26±0.54),(3.17±0.41)μg·mL-1;tmax分别为(1.42±0.65),(1.62±0.75)h;t1/2分别为(29.75±4.89),(30.34±4.67)h;AUC0-120h分别为(131.4 ±23.4),(135.2±20.6)μg·mL-1·h;AUC0-∞分别为(140.5±26.3),(145.0±23.6)μg·mL-1·h.受试制剂相对于参比制剂的生物利用度为(97.2±7.6)%.结论 2种制剂具有生物等效性.     

国产头孢克肟胶囊的人体药动学及其生物利用度研究

目的: 评价头孢克肟国产胶囊剂和参比胶囊在人体内是否生物等效.方法: 采用高效液相色谱法测定18名健康受试者随机、交叉单剂量口服200mg头孢克肟受试或参比胶囊后血浆头孢克肟浓度.结果: 国产头孢克肟胶囊剂和参比制剂的AUC0-t均值分别为(15.918±5.591)和(15.873±4.887) mg·h·L-1, 实测Cmax均值分别为(2.331±0.781)和(2.276±0.704)mg·L-1, 实测Tmax均值分别为(4.500±0.618)和(4.278±0.752)h. 受试国产头孢克肟胶囊的相对生物利用度为(103.5±33.6)%. 结论: 经统计学分析,受试制剂和参比制剂具有生物等效性.     

注射用头孢他啶在健康人体的生物等效性

目的:建立头孢他啶血浆浓度的测定方法,并评价注射用头孢他啶试验与参比制剂是否生物等效。方法:20名健康男性志愿者随机分为2组,采用开放、随机、双周期、自身对照交叉试验设计,对受试者进行单次肌内注射给药,两周期间的洗脱期为3d;采用高效液相色谱法测定头孢他啶经时血药浓度,利用DAS Ver2.0程序计算药动学参数并进行统计分析。结果:头孢他啶参比制剂(含头孢他啶1.0g)和试验制剂(含头孢他啶1.0g)的主要药动学参数Cmax分别为(27.5±5.5)mg.L-1和(27.6±5.4)mg.L-1,tmax分别为(1.2±0.5)h和(1.2±0.5)h,t1/2分别为(2.3±0.4)h和(2.15±0.26)h,AUC0-10分别为(115.3±16.8)mg.L-1.h和(108.2±19.5)mg.L-1.h,AUC0-∞分别为(122.4±16.7)mg.L-1.h和(113.7±20.2)mg.L-1.h。2组间Cmax、AUC0-10、AUC0-∞、tmax的差异均无显著性(P>0.05);试验制剂的Cmax、AUC0-10和AUC0-∞的90%可信区间均未超出参比制剂的80%～125%范围。试验...