国际多中心临床试验在中国

文章综述了药物临床试验在国内外的发展概况，剖析了中国在开展国际多中心临床试验中具备的优势及面临的机遇与挑战，并就如何在中国开展国际多中心临床试验提出相关的建议和对策。     

国际多中心临床试验的护理管理

该文从研究护士的选择及培训、试验药物管理、受试者管理3个方面阐述抗肿瘤药物国际多中心临床试验的护理管理工作,以期建立国际多中心临床试验护理工作的规范化、科学化管理体系。     

月经间期放置宫内节育器(IUD)是否需要宫颈扩张并能导致高的脱落率吗?

过去对放置IUD困难的病例偶尔扩张宫颈以促进IUD放入,但需要扩张宫颈的有关病人的表现,以及扩张是否增加IUD早期脱落的危险很少研究,本文应用和分析了1972年以来,FHI(Family Health Iternational)与国际多中心IUD临床试验协作的大量IUD资料以回答此问题。到1987年3月,49个中心已作了50例或多于50例在月经间期放置IUD,37个中心报道至少有1例行宫颈扩张,参与这次分析的,以1个中心已作了10     

我国新型冠状病毒肺炎临床试验的特点

 目的 分析我国开展的新型冠状病毒肺炎（简称"新冠肺炎"）临床试验的特点,发现可能存在的问题,为临床试验设计者及政策制定者提供一定的参考。方法 收集2020年2月23日24点之前在中国临床试验注册中心官网和美国ClinicalTrials.gov官网注册的新冠肺炎临床试验数据,使用DDA软件进行数据清洗,采用SPSS 18.0对临床试验各特征变量进行描述。结果 我国第1项新冠肺炎临床试验注册时间为2020年1月23日,截至2020年2月23日24点我国共注册240项新冠肺炎临床试验,其中多中心研究62项（25.83%）。共有157个机构参与临床试验,其中医疗机构最多（122个）,参与机构地理分布前5名依次为北京、湖北、广东、浙江、上海。临床试验参与患者的年龄主要以成年人（15~64岁）/老年人（≥65岁）为主（63.75%）,研究类型主要以干预性研究为主（75.42%）,干预措施主要以药物为主（68.51%）,经费来源主要以自筹为主（25.00%）。181项干预性研究所处阶段以0期（70项）和Ⅳ期（49项）为主。结论 目前我国开展的临床试验数量多,但机构合作较少,干预措施和试验药物种类不聚焦,招募人数不尽合理,参与机构及经费来源多样化。     

实验室化验值正常范围标化方法探讨

目前国外发达国家多中心临床试验均使用中心实验室进行实验室指标的检测，可大大提高检验结果的可靠性。但我国由于经费、标本储存等诸多原因，大多数临床试验实验室指标的评价不能采用国际通用的中心实验室，而代之以在每个临床单位各自的实验室进行。而各中心可能由于测试仪器、     

硝苯地平控释片治疗冠心病的国际临床研究-ACTION研究

ACTION研究是世界上第一个用长效钙通道阻滞剂(CCB)与安慰剂对照来治疗稳定型心绞痛的大规模国际多中心临床试验.2004年8月,欧洲心脏病学会(ESC)年会公布了此项研究结果.证实了硝苯地平控释片(拜心同)长期治疗稳定型心绞痛卓越的安全性以及给患者带来的心血管预后的益处.     

非劣效国际多中心临床试验中的一致性评价

目的探讨非劣效国际多中心临床试验中的一致性评价问题,为设计非劣效国际多中心临床试验提供参考。方法我们提出了调整检验水准、基于μ_(all)构造距离比值和基于μ_(all)构造距离比值3种一致性评价方法,并采用蒙特卡罗模拟非劣效临床数据,比较不同参数变化对一致性概率的影响。结果三种方法中,检验水准、比例、设定的处理效应的增大,界值减小,都会使一致性概率增大。结论在试验设计阶段,三种方法均可提供有用的参考,三种方法有各自的优缺点,可依据具体情况选择合适的方法。     

提高鼻咽癌患者生存质量有新模式

正在不久前召开的美国临床肿瘤学年会上,广州中山大学肿瘤防治中心马骏教授应邀报告了一项由中国学者独立完成的肿瘤学研究。这是一项多中心、前瞻性的三期临床试验,首次建立了鼻咽癌放化疗后使用卡培他滨维持治疗的新模式。这项研究成果已在国际医学期刊《柳叶刀》上发表。     

新药临床试验中的损害责任认定

案例背景 2006年2月,原国家食药监局批准某制药公司的某种新药进行国际多中心临床试验.2006年3月,该制药公司与某医院签订临床试验协议,约定"某制药公司希望某医院研究机构在研究者的指导与监督下,在骨科手术中,调节凝血机制,预防深静脉血栓和肺栓塞发生;采用对照、随机、双盲试验,在行选择性全膝关节置换术的患者中,研究该新药对静脉血栓栓塞的预防作用".     

多中心多组临床试验的设计入路

目的本文提出一种用于多中心多组临床试验的设计入路,并同Cochran入路以至Mantel-Haenszel入路作以比较.方法以四格表卡方统计量为起点,将组数由2推广到大于2,层数由1到大干1,得到多层多组非中心参数表达式和检验统计量.结果本文入路计算简便,设计灵活,层数组数不受限制,可作非等层非等样本设计.相比之下,Cochran入路几乎不能用于3组以上,Mantel-Haenszel入路更限于等层设计.对于3中心3组等层设计,本文入路结果比Cochran入路大0到4,至于Mantel-Haenszel入路,为-3到1.本文入路结果多介于后二者之间.结论本文入路可用于多中心多组临床试验的设计.     

体外诊断试剂临床试验质量保证措施研究

目的:分析体外诊断试剂临床试验中的质量问题,研究制定其质量保证提升措施.方法:汇总医院体外诊断试剂临床试验项目自查发现的质量问题并进行分类,利用帕累托图对其进行统计、分类和分析,确定临床试验中存在问题的主要类型,应用鱼骨图进行根因分析,从试验设计、试验实施和数据总结与报告环节制定质量提高措施.结果:在选取的2013-2...     

北京医药产品临床试验现状分析及对策

随着药品临床实验管理国际统一标准的逐步形成,我国逐步建立了药品监督管理体系和临床实验机构,开始进行规范的药品临床实验。本文对北京的临床药理基地进行了系统调研,找出阻碍临床试验发展的问题,并提出促进北京医药产品临床试验发展的对策与措施。     

Recommendations for reporting randomized controlled trials of herbal interventions: Explanation and elaboration

Controlled trials that use randomized allocation are the best tool to control for bias and confounding in trials testing clinical interventions. Investigators must be sure to include information that is required by the reader to judge the validity and implications of the findings in the reports of these trials. In part, complete reporting of trials will allow clinicians to modify their clinical practice to reflect current evidence toward the improvement of clinical outcomes. The consolidated standards of reporting trials (CONSORT) statement was developed to assist investigators, authors, reviewers, and editors on the necessary information to be included in reports of controlled clinical trials. The CONSORT statement is applicable to any intervention, including herbal medicinal products. Controlled trials of herbal interventions do not adequately report the information suggested in CONSORT. Recently, reporting recommendations were developed in which several CONSORT items were elaborated to become relevant and complete for randomized controlled trials of herbal medicines. We expect that these recommendations will lead to more complete and accurate reporting of herbal trials. We wrote this explanatory document to outline the rationale for each recommendation and to assist authors in using them by providing the CONSORT items and the associated elaboration, together with examples of good reporting and empirical evidence, where available, for each. These recommendations for the reporting of herbal medicinal products presented here are open to revision as more evidence accumulates and critical comments are collected.     

The concomitant use of radiotherapy and chemotherapy for the treatment of solid malignant tumors

Various clinical trials carried out during the last few decades have clearly demonstrated that the concomitant use of radiotherapy and chemotherapy significantly improves local control in a variety of advanced solid tumours. In most of these trials where an improvement was noted, cisplatin was used in addition to radiotherapy either on its own or in combination with other cytostatics. This has led to improved survival rates in head and neck, lung and cervical cancer. For these solid tumours, the interaction of radiotherapy with chemotherapy appears to be schedule dependent, as no such an improvement was observed if chemotherapy was given prior to or after radiotherapy. A major advantage of this combined therapy is that a structure-preserving treatment for patients with advanced larynx or anal cancer is more often possible. Major further improvement can be expected from the design and use of new drugs that influence the pathways leading to cell death after irradiation.     

Key multiplicity issues in clinical drug development

Much progress has been made over the past decade with the development of novel methods for addressing increasingly more complex multiplicity problems arising in confirmatory Phase III clinical trials. This includes traditional problems with a single source of multiplicity, for example, analysis of multiple endpoints or dose–placebo contrasts. In addition, more advanced problems with several sources of multiplicity have attracted attention in clinical drug development. These problems include two or more families of objectives such as multiple endpoints evaluated at multiple dose levels or in multiple patient populations. This paper provides a review of concepts that play a central role in defining and solving multiplicity problems (error rate definitions) and introduces main classes of multiple testing procedures widely used in clinical trials (nonparametric, semiparametric, and parametric procedures). The paper also presents recent advances in multiplicity research, including gatekeeping procedures for clinical trials with multiple sets of objectives. The concepts and methods introduced in the paper are illustrated using several case studies on the basis of real clinical trials. Software implementation of commonly used multiple testing and gatekeeping procedures is discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Application of quality improvement theory and process in a national multicenter HIV/AIDS clinical trials network

Effective clinical trials depend on the production of scientifically sound data. Clinical research coordinators monitor various activities to assure that data meet standards for timeliness and quality. Traditional methods of assuring data quality are less than optimal because they are based on correcting mistakes after they occur. Because they are focused on problem prevention, the techniques of continuous quality improvement represent a more effective means of maintaining high quality of data. This article describes the means by which principles of continuous quality improvement were incorporated into an HIV/AIDS clinical research network, as well as outcomes associated with these efforts.     

临床营养研究中随机对照研究质量评价

目的评价两种主要临床营养期刊中随机对照试验（RCT）的质量。方法查阅2000～2008年《中国临床营养杂志》和《肠外与肠内营养》发表的RCT研究，按Cochrane协作网标准评价，并进行Jadad评分。结果两种期刊共发表238篇RCT研究，Jadad评分为（1．65±0．82）分。高质量RCT仅28篇（11．76％），评分为满分5分的仅5篇（2．10％）。随机分组的方法、组间可比性、纳入排除标准、盲法、撤除和退出的数量和理由、样本含量等方面存在各种问题。结论国内临床营养领域RCT研究的设计和质量控制还存在不足或欠缺，水平尚待提高。     

The smallest worthwhile effect of nonsteroidal anti-inflammatory drugs and physiotherapy for chronic low back pain: a benefit–harm trade-off study

ObjectiveThe aim of this study was to determine the smallest worthwhile effects of two treatments for nonspecific low back pain (LBP).Study Design and SettingThe benefit–harm trade-off method was used to estimate the smallest worthwhile effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and physiotherapy for LBP. Patients seeking care for chronic LBP were interviewed by telephone before treatment commenced and 4 weeks later.ResultsPatients need to see a median of 30% (interquartile range [IQR]: 10–40) more improvement in pain and 20% (IQR: 10–40) more improvement in disability than would occur without intervention to perceive the effect of NSAIDs are worthwhile. They would need to see 20% (IQR: 0–30) more improvement on pain and disability over natural recovery to perceive that the effect of physiotherapy was worthwhile. There was no difference in estimates of the smallest worthwhile effect elicited at baseline and 4 weeks later.ConclusionsPeople with chronic back pain need to see larger effects on pain of NSAIDS than physiotherapy to consider the effects of these interventions worthwhile. These estimates of the smallest worthwhile effect can be used to interpret the findings of clinical trials and to design adequately powered clinical trials.     

Lessons learned from clinical trials evaluating pneumococcal conjugate vaccine efficacy against pneumonia and invasive disease

This article discusses lessons learned from clinical trials with pneumococcal conjugate vaccines (PCVs). A review of major clinical trials investigating PCV efficacy, this article provides the context to explore challenges associated with studying pneumococcal pneumonia and vaccine efficacy, particularly related to non-bacteremic disease, serotypes, and radiograph interpretation. Throughout these clinical trials, improving the pneumonia diagnosis specificity increased vaccine efficacy estimates. Additional analysis suggests this improvement may come at a cost of detecting much less of the disease burden. The article concludes with a discussion of the potential value of C-reactive protein as an adjunctive marker in measuring PCV efficacy against non-bacteremic pneumococcal pneumonia.