GCP的基本原则(中英文对照)

 1.1        THE BASIC TENETS OF GCP

GCP的基本原则

The primary reason for the presence of a GCP code of practice is to protect human rights. If this simple principle could be remembered at all times throughout the research process, many of the so-called vagaries of GCP could be resolved. Unfortunately, it is not so easy to keep this principle foremost when one is trying to get a job done or if there is a conflict of interest. Collecting honest and accurate data is a major part of GCP to ensure that data have integrity and valid conclusions may be drawn from those data. Data should be reproducible: that is, if the study were to be conducted in a similar population using the same procedures, the results should be the same. After all, the results of clinical research will be imposed on new patients in the future. To help assure us all of the integrity and reproducibility of research results, the whole process should be transparent and that means that everything must be documented so that an external reviewer can verify that the research was actually conducted as the researchers reported that it was conducted. Many systems and processes must be in place to implement GCP and the documentation must clearly indicate compliance with those systems (Checklist 1.1-1).

GCP出现的最基本的原因是为了保护人权，如果这些简单的原则能够在整个研究过程中被记住，许多所谓的对GCP的偏离行为都能够解决，遗憾的是，当一个人努力去完成一项工作或存在利益冲突时，保持这个基本原则并非易事。收集真实的，准确的数据是GCP主要工作之一，以确保从这些数据中得出完整和有效的结论。这些数据应该是可重现的，就是说，如果用相同的程序应用到相似的人上，结论应该是一致的。毕竟，这样的临床研究结论将来要应用到新的病人身上。为了确保临床研究结果的完整性和重现性，整个过程应该是透明的，也就是说，每个操作必须被记录，以便外部审查者能够确认研究确实是按临床研究报告那样进行的。执行GCP需要制订许多系统和过程，记录的文件必须清楚表明其与这些系统的一致性（见表1.1-1）。 

 Checklist 1.1-1. General Systems and Procedures for Implementation of GCP                    

表1.1-1 GCP实施的一般系统和过程 

The following systems and procedures must be established by clinical

researchers to ensure compliance with GCP requirements:

为了确保研究与GCP要求的一致性，临床研究者必须建立下面的系统和程序。

l        Planning: studies must be conducted for valid (ethical and scientific)

   reasons;

计划：研究必须按照适当的目的进行（伦理的和科学的）

l        Standard operating procedures: research procedures must be declared in writing so that reviewers can determine the standards which are being applied and so that users have a reference point;

标准操作程序：操作规程必须书面发布，以便审查者有一个判断的标准以及使用者有一个操作参考。

l        Qualified personnel: all personnel (sponsor/CRO and study site) must   be experienced and qualified to undertake assigned tasks. Documentation of qualifications and training must be evident.

研究人员资格：所有的人（申请人/CRO和研究基地）必须是有经验和资格承担分配的任务，必须有相应的资历和培训文件。

l        Ethics committee review and approval: all studies must be independently reviewed by ethics committees/IRBs, to assess the risk for study subjects, before clinical studies begin. Review must continue throughout the study.

伦理委员会审批：临床研究开始之前，为了评估研究对受试者的风险，所有研究必须经伦理委员会或IRB独立审查，审查必须贯穿整个研究过程。

l        Informed consent: all study subjects must be given the opportunity to personally assess the risk of study participation by being provided   with certain information. Their assent to participate must be documented.

知情同意：必须告知所有受试者足够的信息，让其有机会自己评价参加研究的风险，并且记录他们的同意。

l        Well-designed study: all studies must have a valid study design documented in a protocol so that it can be fully reviewed by all   interested parties. The data collection plans, as described in the CRF, are part of the protocol.

精心设计的研究：为了所有感兴趣人员能够充分审查方案，所有的研究方案中必须说明有效的研究设计方法.设计作为方案的一部分，像CRF表格中描述的数据采集计划，也应作为方案的一部分。

l        Monitoring: a primary means of quality control of clinical studies   involves frequent and thorough monitoring by sponsor/CRO personnel;

监查：临床研究质量控制的主要方法包括申办者/CRO人员频繁的和全程监查。

l        Control of study medications/devices: the product being studied must be managed so that study subjects ultimately receive a safe product and full accountability can be documented;

研究用药物/器械的管理：研究用品必须被管理，以便受试者最终使用的是安全的产品，研究用品使用必须记录。

l        Integrity of data: data must be honest. Data must be reviewed by site personnel, monitors and data processing personnel.

数据的完整性：数据必须真实，必须经试验人员，监查员，和数据处理人员审查。

l        Quality assurance: systems for assuring quality and for checking  quality must be established and followed at all stages;

质量保证：质量保证和检查系统必须建立，在整个试验过程中必须遵守。

l        Archives: documentation of research activities must be securely   retained to provide evidence of activities.

存档：研究活动的文件必须被安全保存，作为活动的证据。 

1.2 THE GENERAL REGULATORY FRAMEWORK FOR GCP

1.2 GCP的基本规章制度

(This section is only intended to provide a fairly general review of the regulatory framework and the interested reader is advised to seek expert advice elsewhere.)

本节仅打算总体探讨规章制度，感兴趣的读者建议去别处参考专家的建议。

   The regulatory framework for compliance with research procedures has essentially developed in the last two decades, except for the US where rules were first established in the 1930s. Most countries in the European Union, other countries in Europe (e.g. Hungary, Poland and Switzerland) and Japan have regulations on GCP. Other countries have regulations controlling clinical studies, but not specifically directed to GCP, although they have guidelines on GCP (e.g. Canada and Australia). In this decade, an attempt has been made to harmonize the requirements in the form of an ICH GCP document which has been adapted as regulation by many countries. Some countries have no guidelines or regulations, but guidance for researchers has been provided by organizations such as CIOMS and WHO.

研究遵循的规章制度在过去的二十年里已经得到本质上的发展，除了美国的法规是在十九世纪三十年代建立外，其他的欧盟国家（例如：匈牙利，波兰，瑞士）和日本也有GCP法规。其他的国家有法规控制临床研究，但没有明确表明其是GCP法规，尽管他们有GCP指南（例如加拿大和澳大利亚）。在这的十几年，ICH  GCP 文件作为一个尝试，用来协调这种要求，已经被许多国家作为法规采用。一些国家没有指南或法规，但是一些组织也提供一些研究者指南，比如国际医学组织理事会和世界卫生组织。 

   Many researchers try to distinguish between guidelines and regulations, claiming that it is only necessary to comply strictly with the latter. However, if put to the test in court, guidelines would assume a high status: it is best to take them seriously. Much of medical practice is not regulated, but in cases of negligence for example, the court will review the 'state of the art' as the expected standard, much of which is documented in guidelines. The same is true for GCP.

许多研究者尽力区别指南和法规，主张仅仅严格遵守法规就可以了，然而，如果诉诸法庭，指南则成为高级别的依据，最好认真的对待他们。许多医疗实践没有规范，如果万一疏忽，法庭将 “最高级别”的指南作为预期的标准来判定，其中大部分在指南中已经规定相应的规范，GCP指南也是一样的。

    In the last few years, there has been increasing interest in inspection of GCP compliance. Although this has been a regulatory requirement in the USA for many years, inspectorates have only just started in countries such as Austria, Denmark, France, Finland, Germany, Japan, The Netherlands, Norway and Sweden. There are problems in finding good inspectors, in deciding on the final standards for inspections and in imposing sanctions for non-compliance. An interesting recent development has been the initiation of inspections in Europe by the central regulatory authority, the European Medicines Evaluation Agency (EMEA).

在过去的几年里，对GCP依从性的视察正在增加，尽管这在作为美国法规要求已经许多年了，视察仅在澳大利亚、丹麦、法国、芬兰、德国、日本、荷兰、挪威、瑞典等国家实行，在寻找好的视察员、指定最后的视察标准和对不符合规范的处罚等方面还有些问题。最近，让人兴奋的变化是，欧洲由统一的管理机构来启动视察（即欧洲药品评价中心）。

    Regulation of compliance with requirements by ethics committees is also developing in some parts of the world (e.g. France and Denmark). To date, the US FDA is the only authority which is actively checking on the activities of IRBs by inspection and licensing.

在世界的许多地方（例如：法国，丹麦），对伦理委员会遵循要求的法规也正在制订中，迄今为止，仅有美国FDA当局在通过视察和认证来积极检查IRB的工作。 

   For non-compliance with regulations, only the USA has imposed serious sanctions to date. The "blacklist' (list of all investigators who have been found to be non-compliant and were barred from clinical research for FDA submissions) is publicly available through freedom of information rules. The USA has vast experience (thousands of inspections) compared to the handful of inspections in other countries. For example, at the time of writing this book, the UK has only conducted a few voluntary inspections.

对于不遵守法规，迄今为止，仅有美国颁布了严肃的处罚规定。黑名单（那些曾经被发现依从法规，并且被禁止进行FDA申报的临床研究的研究者列表。）是公众利用信息自由法可看到的。相对其他国家少量的视察员来说，美国有大量的经验（数以千计的审查），举例来说，在写本书的时候，英国仅仅进行了少量的自主的视察。 

   The consequence of non-compliance with GCP requirements may be serious for the researcher and the sponsor, but in this book we are most interested in the consequences for the study subjects. We have published findings elsewhere to suggest that there could be many improvements in compliance as the events of non-compliance we observe cause us great concern. Therefore, we have included many examples of non-compliance in this book which arise from our own experience as auditors. We hope they are helpful in sensitizing the reader to some serious issues.

对研究者和申办者来说，不依从GCP要求的结果可能是严重的，但是本书我们最大的兴趣是受试者的结果。因为我们观察到的不依从性已经引起了我们极大的关注，并在别处发表了这些发现，提示在依从性方面需提高。因此，我们在本书中收集了一些在我们稽查中发现的不依从的例子，我们希望，这些例子有助于提高读者对这类严重事件的敏感性。