医疗器械临床试验贝叶斯统计应用指导原则简介

<正>美国FDA器械与辐射防护中心(center for devices and radiological health,CDRH)于2010年2月5日发布了《医疗器械临床试验贝叶斯统计应用指导原则》[1]。这是继2006年5月23日FDA发布该《指导原则》草案后[2],经过近3年的征求意见和深入研讨后所形成的官方指导性文件。《指导原则》不仅对贝叶斯临床试验设计、数据分析、上市后监测等统计学问题进行了     

对《有毒作业分级》在职业病危害评价工作中的应用思考

根据我们在评价工作中遇到的问题,对照有关规范标准要求,我们认为《有毒作业分级》(GB12331-90)已不适应职业病危害评价工作要求,应当尽早对该标准进行修订。主要修订方面为:①有害物质的采样和分析方法的修订;②有毒作业分级原则的修订;③同时应考虑毒物的皮肤吸收系数、毒物的联合作用系数等指标。     

浅谈体外诊断试剂临床试验方案的设计

本文将结合国家食品药品监督管理局发布的《体外诊断试剂临床研究技术指导原则》及北京市药品监督管理局发布的《北京市第二类体外诊断试剂临床试验指导原则》,浅谈体外诊断试剂产品临床试验方案的一些设计原则和数据的统计分析方法。     

闽东宫颈癌普查中HPV E6/E7 mRNA及DNA的应用研究

目的:分析超薄液基细胞学(LCT)技术在宫颈癌筛查中的应用.方法:采集554例LCT本,检测HPVE6/E7 mRNA,同时检测HPV E6/E7 DNA;对结果的总体分布情况及在不同细胞学级别分布情况行统计学分析.结果:以病理结果为标准,43例中不同级别的HPV E6/E7 mRNA,DNA检测情况比较,差别无统计学意义;以细胞学检测为标准,231例不同级别中HPV E6/E7 mRNA及DNA检测情况,除ASCUS外,其余级别两种检测方法差别无统计学意义;34例ASCUS标本同时行病理活检,以CIN为阳性结果,两种检测方法对阳性结果的判读,差别无统计学意义.结论:宫颈癌筛查中检测HPV E6/E7mRNA对于宫颈癌筛查具有一定的临床意义.     

《临床医院感染学》第二版征订启事

中南大学湘雅医院医院感染控制中心在医院领导支持下 ,组织临床各科专家对《临床医院感染学》(1998年初版 )进行了修订。内容除医院感染的基础知识及进展外 ,还体现了临床各科感染性疾病的新进展 ,后者如新传染病、脓毒症等 ;并根据国内外医院感染控制指南更新了感染控制的指导方案 ,如呼吸机相关感染、抗菌药物临床应用指导原则 ,以及相关检验方面内容 ,也包括了卫生部新颁发《消毒技术规范》、《医院感染管理规范》、《医疗废物管理条例》等实践措施。在每章后附有参考文献 ,以便读者能阅读到原文。本书包括理论与实践两部分 ,不仅可作为…     

《金属接骨板内固定系统产品注册审查指导原则（2021年修订）》修订内容及审评关注点解析

该研究对《金属接骨板内固定系统产品注册审查指导原则（2021年修订）》相较于原指导原则的修订内容进行了简要介绍,主要包括注册单元划分的原则、产品技术要求的主要性能指标、物理和机械性能研究及临床评价资料。同时,基于金属接骨板内固定系统产品的审评经验积累并结合现行审评要求对该类产品在审评过程中的主要关注点进行解析,以期为金属接骨板内固定系统产品注册申报及技术审评提供指导。     

第一讲如何在研究设计中体现重复、对照、随机原则

总编按语期刊质量特别是学术水平是期刊赖以生存和发展的必备条件,是期刊的生命。据两位作者分别分析5种中华医学会系列杂志 1985年与1995年发表的640篇和954篇论著的研究设计和统计学方法应用,发现其中多数文章属描述性分析。1985年的论著中横断面研究和病例报告占50%以上,临床试验的比例仅占5.6%,其中随机对照试验比例为1.3%;到1995年临床试验的比例增至11.3%,随机对照试验的比例增至 4.2%。能正确使用统计方法的文章在1985年只占22%,到 1995年增至46%。《中华预防医学杂志》所发表的论文在科研设计、统计学分析、结果解释等方面也不同程度地存在一些问题。这表明,尽管在国内中华医学会系列杂志具有较高的学术领先地位,仍在已刊出论文中存在不少的统计学方法误用问题,说明医学工作者对医学统计方法的掌握与应用水平急需提高。为适应这种需求,在本刊举办《医学研究统计方法应用》系列讲座,组织国内造诣较深的医学统计学者,以中华医学会系列杂志中的实例为主,总结其中统计方法的应用经验与问题,提出正确应用时必须注意的问题,为医学工作者在医学研究中正确应用统计方法提供参考。由于我们的指导思想是注重实际,强调正确应用,因而涉及到一些实例,这是学术上探讨的需要。专题讲座的内容有研究设计的统计学原则、随机对照研究、样本的确定、数据类型与质量控制、常用的数据统计分析方法、统计图表的正确应用、医学参考值范围的确定、重复测量结果的比较、随访资料分析、Meta分析、循证医学、统计结果表达与解释、常用数据库软件与统计软件介绍等。每篇后面还附有围绕中心内容的测试题,以辅助读者自学与掌握讲座的内容。这仅是一次尝试,由于组稿时间紧,经验不足,难免有不足之处,还望广大读者和同道们及时发现问题予以指出,帮助我们把讲座办得更有成效。第四军医大学徐勇勇教授对本讲座做了周密地构思,在此对徐勇勇教授和为本讲座做出贡献的医学统计学者们表示衷心的感谢。 研究设计的内容分专业设计和统计设计两部分。专业设计主要是选题,建立假说、确定研究对象和技术方法等。统计设计则是围绕专业设计,确定统计设计类型、样本大小、分组方法、统计分析指标及统计分析方法等。 医学研究按照有无人为施加的干预,又分为实验性研究和观察性研究两大类型。观察性研究是以客观、真实的观察为依据,对观察结果进行描述和对比分析;实验性研究是在排除其他因素影响的条件下,推论干预措施的因果效应。这两类研究在研究设计和统计结果的解释上有很大不同,一定要认真区别。研究设计必须遵循的统计学原则是“重复、对照、随机化”,即要有一定数量的重复观察样本、设立对照组、做到随机化分组或随机抽样。     

《全国医疗服务价格项目规范》中临床诊疗服务项目修定原则

通过对《<全国医疗服务价格项目规范>(试行)2001年版》及《<全国医疗服务价格项目规范>(新增和修订项目)2007年版》中临床诊疗服务修订内容的研究,从框架、栏目、内容以及计费方式等方面对修订的情况进行分析阐述,对临床诊疗服务的修订原则进行总结,为医疗服务项目的合理定价提供参考.     

对《保健食品注册管理办法》修订稿的解析及思考

《保健食品注册管理办法(试行)》被国家食品药品监督管理总局初步起草对其进行修订,该文在阐述保健食品注册法规历史沿革的基础上,对修订稿的内容进行了部分解读及思考,旨在通过对比新旧注册管理办法的异同,指导注册申请人进一步规范保健食品注册行为。     

制订和更新临床诊疗指南的方法(摘要)

以往研究结果证实，临床诊疗指南是良好医疗决策的重要依据，澳大利亚国家卫生与医学研究委员会出版了修订后的《临床诊疗指南的制订、实施与评估指导》。以下我们摘录了其中部分内容，包括：主要原则、指导原则的制订、证据的水平和发布。     

The impact of the international guideline entitled Statistical Principles for Clinical Trials (ICH E9)

At the time of writing, the ICH E9 Note for Guidance entitled "Statistical principles for clinical trials" has been in force in Europe, Japan and the U.S.A. for almost a year. The purpose of this paper is to review the initial progress of E9 in terms of its degree of acceptance and also in terms of any early problems which have emerged. A different means of exploring these questions has been adopted in each of the three regions. From Europe there is a regulatory perspective on statistical issues which have been found to be incompletely covered within E9 and which have been important for specific regulatory decisions. From the U.S. there is a report of the results of a survey of U.S. pharmaceutical industry opinion concerning the effect of E9 on statistical practice in drug development. From Japan there is a discussion of the shortage of qualified statisticians in Japan and the difficulties that this causes when trying to implement E9. Some overall conclusions are drawn.     

Implementation of good clinical practice guidelines in vaccine trials in developing countries

The practicalities when applying the ICH GCPs (International Conference on Harmonization 1996 Good Clinical Practices [EU, MHLW, FDA. International Conference on Harmonization Guideline for Good Clinical Practice; 1997] in less developed countries (ldcs) are seldom discussed and we found no guidelines as how to "adapt" them. Below we illustrate how ICH GCP principles can be implemented in different settings. We have recently conducted in Asia (Hechi, China; Karachi, Pakistan; Hue, Vietnam; North Jakarta, Indonesia and Kolkata, India) large-scale cluster-randomized effectiveness evaluations of the Vi polysaccharide typhoid fever vaccine (Vi PS project) among approximately 200,000 individuals(1)[Acosta CJ, Galindo CM, Ali M, Abu-Elyazeed R, Ochiai RL Danovaro-Holliday MC et al. A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design. TMIH 2005;10(12):1219-1228]. There is no doubt on the importance of ICH GCP in its contribution to ethical and scientifically sound clinical research. However, when the ICH GCP is implemented in ldcs some considerations must be made in order to adequately tailor them. Vaccine trials in ldcs are a frequent setting for such challenges because of the increased global interest conducting health research in such countries. The ICH GCP principles are discussed below within the framework of this recent typhoid fever vaccine study experience.     

ICH E9 guideline 'Statistical principles for clinical trials': a case study

The International Conference on Harmonization (ICH) E9 guideline 'Statistical principles for clinical trials' was adopted by the Committee for Proprietary Medicinal Products in March 1998, and consequently is operational in Europe. It has also been adopted in the U.S.A. and Japan. The aim of this paper is to relate the problems encountered during a recent regulatory submission to those discussed in the ICH E9 guideline. Statistical principles discussed in the guideline, but not comprehensively addressed when the clinical development programme was initiated in the mid-1990s, will be reviewed. The impact of each issue on the approvability of the dossier will be discussed, together with recommendations on how to avoid such problems with other ongoing clinical development programmes.     

制定临床医学指南需要指南

目前,世界许多国家都通过开发本国的临床医学指南来指导临床工作,从而提高整体的临床实践水平。与欧美发达国家医学专业团体编写的临床医学指南相比,我国指南制定工作仍有不足之处。分析这些不足之处产生原因,除了指南制定者对指南的理解不正确之外,主要原因是我国目前还没有制定统一的、规范的指南开发程序,也就是制定临床医学指南的指南。当然缺乏国内的随机对照研究（RCT） 和 队列研究资料也是我们明显的薄弱之处。指南的开发程序是以开发指南为目的设计的结构运行和协调机制,通常涉及（1）指南的制定程序;（2）指南的传播途径;（3）指南的合理应用办法;（4）指南的评价反馈与更新机制等几个方面。随着国家临床医学指南开发程序的建立,我国指南制定的项目选择会更加合理,选择范围会逐步扩大,指南开发速度会稳步加快,指南水平和实用性会大大提高。     

The assessment of the economic return from controlled clinical trials

Clinical trials can be considered health interventions as their primary aim is to impact on the health of a population. Given that resources are scarce for both health care and health related research, trials could be designed such that they can be demonstrated to be cost-effective, i.e., the costs of conducting the trial are justified given the forecasted long-term benefits.We demonstrate how a model can be used to predict the cost-effectiveness of undertaking a clinical trial comparing alternative regimens of colorectal cancer follow-up.The model forecasts costs and survival under two scenarios,with and without conducting a clinical trial, with the outcome assessed in terms of years to payback for the clinical trial.The methodology shown can be used both to provide information on appropriate trial design and/or in prioritizing between potential trials. Douglas Coyle Clinical Epidemiology Unit, Ottawa Health Research Institute, 1053 Carling Avenue,Ottawa Hospital,Ottawa, Ontario K1Y 4E9,Canada, e-mail: dcoyle@ohri.ca     

公众对临床试验的认知、实践与态度的调查研究

目的评价公众的临床试验的认知、实践与态度。方法采用匿名的横断面在线调查,共收集702份18岁以上中国公众的有效调查问卷。结果在702名被调查者中,有84.2%听说过临床试验,但是仅有6.0%作为受试者参与过药物临床试验。83.6%的被调查者知道“受试者的隐私和个人信息应该得到充分保护”,仅48.4%的被调查者知道“患者也可以参与设计和发起符合自己需要的临床试验”。41.7%的被调查者“愿意作为志愿者参加临床试验”。回归分析表明“工作/专业领域”“是否作为受试者参与过药物临床试验”“是否有亲人朋友作为受试者参与过药物临床试验”是影响公众参与临床试验意愿的显著因素。结论公众对临床试验的认知程度尚可,但是对于以患者为中心的临床试验发展趋势认识较低。公众的临床试验参与意愿较低,并且受自身专业背景以及相关经历影响很大。有必要开展针对公众的临床试验科普活动,积极发展临床试验公益团体,提升公众临床试验认知水平和参与积极度。     

Case reports and case series from Lancet had significant impact on medical literature

BACKGROUND AND OBJECTIVES: Case reports and case series are often the first evidence of innovative treatment, but clinical trials need to follow to substantiate this evidence. The objective of this article was to evaluate case reports or case series describing innovative treatment concerning their impact. METHODS: Case reports and case series (n < or = 10) from a high-impact journal, The Lancet, published from 1 January 1996 to 30 June 1997, were evaluated according to predefined criteria. To assess publication impact, Pubmed, Science Citation Index, the Register of Current Controlled Clinical Trials, and the Cochrance Controlled Clinical Trials Register were searched. RESULTS: Sixty-four case reports and 39 case series were identified. They were cited in average 17 times (median 6,5; range 0-336). Twenty-Four follow-up trials were identified, nine in the register of current controlled clinical trials. CONCLUSION: Case reports and case series can be well received, and have significant influence on subsequent literature and possibly on clinical practice. Many were followed by clinical trials. Often, though, they report rare conditions for which trials may not be feasible, and more or less explicitly transfer established treatment into other conditions. Overall, there is a strong publication bias favoring positive results, and opportunity should be created for publication of follow-up reports.     

临床预防服务概述

在国外,临床预防医学的发展很快。本文主要阐述了《临床预防服务指南》的制定、组织实施和临床预防服务的发展前景。     

STATISTICAL CONCEPTS IN THE PLANNING AND EVALUATION OF DRUG SAFETY FROM CLINICAL TRIALS IN DRUG DEVELOPMENT: ISSUES OF INTERNATIONAL HARMONIZATION

The assessment of the safety of new drugs during pre-marketing clinical studies is an important and integral part of the drug development and regulatory evaluation process. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a project that brings together the regulatory decision-makers of Europe, Japan and the United States of America and the experts from the pharmaceutical industry in the three regions to seek ways to eliminate redundant and duplicative technical requirements among the developed countries for registering new medicinal substances and products. The ICH is developing guidelines or position papers to achieve the goal of harmonizing technical standards in three broad areas, namely, drug efficacy, safety and quality. Within the area of drug safety, this paper will discuss three of the safety topics because of their relevant statistical framework, and because these topics have not, to date, received any attention by the statistical community. The three issues under consideration by the International Conference on Harmonization (ICH), are. 1. Dose–response information to support drug registration (especially dose/toxicity relationship). 2. Studies in support of special populations; Geriatrics, A Draft Guideline. 3. ICH Draft Guideline 3 on The extent of population exposure required to assess clinical safety for drug intended for long-term-treatment of non-life-threatening conditions'. The ICH special population guideline concerning studies in geriatric patients is closely related to a recent Food and Drug Administration ‘Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs’,⁴ which is another example of a ‘subgroup’ for whom specific interest exists to evaluate drug safety and efficacy.     

医疗器械临床试验准入评估模型构建及应用

依据《医疗器械临床试验质量管理规范》,参考丹麦卫生技术评估中心制定的Mini-卫生技术评估清单,结合医院实际,建立了医疗器械临床试验准入评估模型。该模型主要包括医院评估、器械评估、患者评估、机构评估及经济评估等5项指标、26项内容。实际应用中,确保了所承接的临床试验能在规定时间节点内顺利完成,并保障了试验质量和受益者权益。