体外诊断试剂临床试验检查关注点

为提高监管人员对体外诊断试剂临床试验监督质量，结合体外诊断试剂临床试验及其法规的发展现状，探讨体外诊断试剂与器械临床试验的区别，从生物样本管理等六个方面提出了体外诊断试剂临床试验检查的关注点。同时，以山东省体外诊断试剂临床试验为例，总结目前临床试验存在的问题，分析原因，并提出可从医疗机构、申办者、法规体系建设、监管模式创新四方面入手加强临床试验管理。     

中美医疗器械临床试验监管比较分析

临床试验是保证医疗器械有效性和安全性的重要途径之一。通过对比分析中关两国医疗器械,临床试验监管法规,探讨了两国临床试验监管系统的差异,并提出意见和建议。     

两阶段设计在医疗器械非随机临床试验中的应用

目的介绍两阶段设计的概念、使用流程和注意事项,并以某外周血管支架临床试验为例介绍其在医疗器械非随机临床试验中的应用。方法基于倾向性评分的两阶段设计能使医疗器械非随机临床试验满足随机化和前瞻性的原则。我们以某外周血管支架的非劣效试验为例,介绍两阶段设计的流程和细节。结果两阶段设计解决了非随机临床试验由于非随机所带来的可能的研究偏倚及倾向性评分方法使用过程中的主观不确定性,实现了对随机临床试验的模拟,从而保障了非随机临床试验研究设计和统计分析的客观性和前瞻性。结论两阶段设计能够增加临床试验的可行性,整合高质量的外部数据,缩短试验周期,提高试验效率,最终得到可靠的结论,具有较大的推广价值。     

药物临床试验中申办者和CRO的监管模式研究

药物研发单位(申办者)和合同研究组织(CRO)是药物临床试验的发起者和组织者,是保证药物临床试验质量的关键。我国目前尚未建立申办者和CRO的监管措施和监督检查机制。本课题对国内外药物临床试验监管制度及对申办者和CRO的监管模式和实际监管情况进行了研究比较,收集了上海市自2008年实施药品注册临床试验现场核查以来的核查记录,并对上海市申办者、CRO和临床试验机构进行了调研访谈,对部分省市药品注册监管人员进行了访谈,以大量的研究数据为依据,深入分析了当前国内申办者和CRO开展药物临床试验的现状和执行GCP中存在的实际问题;借鉴国外比较成熟的临床试验监管经验,探讨了适合我国当前国情的对药物临床试验申办者和CRO的监管模式,以期完善国内的临床试验监管制度,保证国内药物临床试验质量,从而保障受试者权益和保证研究结果的科学可靠,并有助于推动国内制药企业走向国际化。     

体外诊断试剂临床试验核查要点解析

<正>国家食品药品监督管理总局根据《医疗器械监督管理条例》、《医疗器械注册管理办法》(食品药品监管总局令第4号)、《体外诊断试剂注册管理办法》(食品药品监管总局令第5号)、《医疗器械临床试验质量管理规范》以及体外诊断试剂临床试验技术指导原则等相关要求,制定了《医疗器械临床试验现场检查要点(2016年)》。2016年6月8号,国家食品药品监督管理总局发布了总局关于开展医疗器械临床试验监督抽查工作的通告     

放射诊疗设备临床试验现状与监管要求探讨

目的通过对放射诊疗设备临床试验中存在问题的分析和讨论,帮助医疗机构和生产厂家了解法律规定,合法开展临床试验,并为监管部门加强管理提供建议。方法梳理监督管理实践中发现的放射诊疗设备临床试验中存在的各类问题;分析医疗器械临床试验、大型医用设备配置和放射诊疗管理相关法律法规中与放射诊疗设备临床试验相关的法律规定;理清合法开展放射诊疗设备临床试验的要求;进一步探讨加强监管的方法。结果放射诊疗临床试验中存在参与单位对法律法规认识不足、安全和防护未受到足够重视、放射源管理有隐患等问题。结论临床试验的参与单位应加强法律法规学习,合法开展放射诊疗设备的临床试验;监管部门应加强管理,保障合法的临床试验,依法处理违法行为。     

药品临床试验电子数据采集(EDC)系统的研究与开发

在临床试验中,临床试验的数据管理工作极其重要,一个新药临床试验完全有可能因为数据质量问题而失败.而优质的数据管理工作不仅为统计分析提供真实可靠、可用性高的数据,为政府相关主管部门提供翔实的原始记录以便于监管,也可以加速临床试验进程,及时发现问题,从而缩短临床试验周期,提高效率并规避风险.数据管理工作的核心是对病例报告表(Case Report Form ,CRF)填写的质量控制.     

我国医疗器械临床试验监管现状分析及对策探讨

医疗器械的临床试验是医疗器械管理中的重要组成部分。一方面,通过临床试验,医疗器械的安全性和有效性得到合理评估,为医疗器械上市提供科学依据。另一方面,临床试验耗时长,花费多,如果管理不当,有可能增加社会成本,给生产企业甚至消费者带来沉重的经济负担,进而影响医疗器械行业的发展。本文分析了我国医疗器械临床试验管理现状及存在的问题,并且提出了一些改革医疗器械临床试验监管的对策建议。     

医院临床试验药物规范化管理的实施

目的介绍该院临床试验药物的规范化管理,为建设试验用药物的管理模式提供借鉴及参考依据。方法从建立临床试验中心化药房管理模式、专职化药物管理人员、建设硬件设施、建立药房管理制度、制定标准操作规程、加强药物临床试验质量管理规范培训等方面,阐述该院临床试验药物规范化管理。结果临床试验药房运行更加标准化,临床试验用药物管理更加规范。结论对构建规范化、科学化的临床试验用药物中心化管理具有重要的现实意义。     

药物临床试验中受试者权益保护机制的探讨

药物临床试验,是新药研发中的重要环节,临床试验的科学准确,决定着创新药物是否能成功开发上市。所以,加强对药品研究过程中临床试验的监督管理,是越来越受关注的话题。过程监管不仅是关注研究进展全过程的规范性,更要关注在研究过程中受试者的权益保护问题。由于我国在药物临床试验管理方面相关的法规起步较晚,本课题将通过对药物临床试验中伦理审查管理模式的探讨、儿童用创新药物的知情同意如何完善以及如何建立在药物临床试验中的意外伤害保险制度等,探索更好地健全药物临床试验中受试者的权益保护机制。     

药物临床试验数据管理的新探索

目的：探讨药物临床试验数据管理的新模式。方法：开发新的药物临床试验数据采集与管理系统。结果：通过管理系统对数据录入校验、在线监督数据挖掘,提高了药物临床试验的效率。结论：药物临床试验数据采集与管理系统是专门针对新药在临床试验过程中的数据采集,以及对这些数据的管理所研发的,是帮助药物临床试验中心方便、快捷和准确地从临床收集药物试验数据。     

Therapeutic cancer vaccines: why so few randomised phase III studies reflect the initial optimism of phase II studies

Immunotherapy is showing promise for the treatment of a range of tumours including prostate cancer, melanoma and non small-cell lung cancer. Phase II trial data has been extremely encouraging with regards both clinical outcome and the investigation of the underlying immunological mode-of-action. However, despite the positive phase II data there remains a high failure rate in late stage clinical trials which, in many cases can be ascribed to inappropriate trial design, poor patient selection and inconsistency in patient management. The potential impact of standard cancer treatments and other factors which may vary within patient populations is discussed. A perspective is provided on the failure of late-stage clinical trials across a range of platforms focusing particularly on melanoma and prostate cancer.     

卫星药房建设提升临床试验质量

试验用药品规范化管理有助于提升临床药物研究水平。从硬件设施、人员配备及资质、文件管理、质量控制等方面建设卫星药房,并采取GCP药房监管模式,实现试验用药品闭环管理。实施后,试验用药品质控问题减少,管理更加规范。卫星药房可作为GCP 药房的补充,确保试验用药品安全,提升临床试验质量。     

Estimation of treatment effect for the sequential parallel design

The sequential parallel clinical trial is a novel clinical trial design being used in psychiatric diseases that are known to have potentially high placebo response rates. The design consists of an initial parallel trial of placebo versus drug augmented by a second parallel trial of placebo versus drug in the placebo non-responders from the initial trial. Statistical research on the design has focused on hypothesis tests. However, an equally important output from any clinical trial is the estimate of treatment effect and variability around that estimate. In the sequential parallel trial, the most important treatment effect is the effect in the overall population. This effect can be estimated by considering only the first phase of the trial, but this ignores useful information from the second phase of the trial. We develop estimates of treatment effect that incorporate data from both phases of the trial. Our simulations and a real data example suggest that there can be substantial gains in precision by incorporating data from both phases. The potential gains appear to be greatest in moderate-sized trials, which would typically be the case in phase II trials.     

Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations. Copyright © 2013 John Wiley & Sons, Ltd.     

肿瘤专科医院药物临床试验质量规范管理体系研究

我国医院开展临床试验存在研究方案设计缺乏科学性,试验过程缺乏规范性,数据质量有待提高等问题。针对我国抗肿瘤药物临床试验现状,提出构建临床试验质量规范管理体系实践路径,包括在试验启动前多方参与共同修订研究方案确保其科学性;在试验过程中建立临床试验制度/SOP体系、质控体系、SAE报告管理体系;在试验后期建立数据质量管理体系、结果评估体系等。     

The IHAT-GUT Iron Supplementation Trial in Rural Gambia: Barriers,Facilitators, and Benefits

Introduction: In most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical trial (termed IHAT-GUT), conducted at the Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM) (abbreviated as MRCG hereof). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in the Gambia. Methods: Individual interviews (n = 17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis. Results: Potential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff, and the local partnership. Conclusions: While facilitators and barriers were identified to conducting this clinical trial in a rural, resource-poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand.     

加强医院药物临床试验质量管理的探索

新药研究是临床医学研究的重要组成部分，也是衡量一个医院科研能力的重要标志之一。近年来，本院逐步认识到加强药物临床试验的管理，完善质控的重要性。因此，为了规范药物临床试验的开展，提高质量，严格按照国家药监局颁布的GCP的相关规定，严格遵循GCP“安全性和科学性”的原则，并实施了一系列的举措，包括制定完善各项制度及标准操作规程，加强全员的GCP知识和相关技能的培训，并逐步推行“三级质控”制度，加强试验药物的管理等等。本文总结了近几年本院实施开展药物临床试验管理及质控方面的经验及不足，力求在今后的药物临床试验工作的开展中，确保各项操作规范，数据完整准确，充分保护受试者的利益，并不断强化过程管理，提高药物临床试验质量。     

An improved method of evaluating drug effect in a multiple dose clinical trial.

In drug development, finding an optimal dose is normally carried out in a phase II trial. A phase III trial will then be conducted to demonstrate that the selected dose is efficacious and safe. As choosing a dose from the phase II trial which has the highest observed response rate could overestimate the true response rate of the selected dose, the data from the phase II study cannot be simply pooled with the data from the phase III study in a final analysis. Therefore, a solution to the overestimation problem needs to be found so that the information obtained from phase II dose finding clinical trials can appropriately be combined with the data in the phase III study. In this paper, the potential overestimation in a multiple dose clinical trial is assessed and a method for correcting this bias is proposed. Simulations show that stepwise over-correction, the proposed method, is better than methods such as Bonferroni's procedure.     

基于潜在狄利克雷分布模型的我国临床试验管理研究热点及其演化分析

目的 分析国内临床试验管理研究领域的研究主题和热点主题的演化过程,揭示其研究现状。方法 本文采用潜在狄利克雷分布模型(Latent Dirichlet Allocation,LDA)对本领域的研究文献进行主题分析,根据主题生命周期坐标图识别热点主题,基于不同发展阶段热点主题所属文献的关键词分析主题内容的演化脉络。结果 国内临床试验管理领域的主要研究主题有13个。按研究内容可分为两类:临床试验的质量管理类和临床试验受试者权益保护类; 按主题的发展类型可分为:5个具有进一步发展潜力的潜在主题、4个具有分化趋势的衰退主题和4个热点主题。热点研究主题的演化脉络既有自身特点,也呈现出一些共性特征。结论 近年来,我国临床试验管理的研究快速发展。热点主题中,临床试验机构管理研究的落脚点从宏观向微观转变、信息管理系统的设计从独立系统转向多系统的融合开发、受试者的权益保护研究的侧重点在发生变化、受试者依从性研究从关注生理向关注心理转变。