ICH-GCP中英文对照 - 图文

ICH 三方协调指导原则 E6 ICH GCP指导原则

INTRODUCTION 前 言

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible.

临床试验管理规范（GCP）是设计、实施、记录和报告涉及人类对象参加的试验国际性伦理和科学质量标准。遵循这一标准为保护对象的权利、安全性和健康，为与源于赫尔辛基宣言的原则保持一致以及临床试验数据的可信性提供了公众保证。

The objective of this ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

ICH-GCP指导原则的目的是为欧盟、日本和美国提供统一的标准，以促进这些管理当局在其权限内相互接受临床数据。

The guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO).

本指导原则的发展考虑了欧盟、日本、美国，以及澳大利亚、加拿大、北欧国家和世界卫生组织（WHO）的现行GCP。

This guideline should be followed when generating clinical trial data that are intended to be submitted to regulatory authorities.

在产生打算提交给管理当局的临床数据时应当遵循本指导原则。

The principles established in this guideline may also be applied to other clinical investigations that may have an impact on the safety and well-being of human subjects.

本指导原则中确立的原则也可应用于可能影响人类对象安全和健康的其他临床研究。

1. GLOSSARY

1. 术语

1.1 Adverse Drug Reaction (ADR) 药品不良反应（ADR）

In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable

possibility, i.e. the relationship cannot be ruled out.

在一个新的药品或药品的新用途在批准之前的临床实践，尤其是治疗剂量尚未确定前，ADR是指与药物任何剂量有关的所有有害的和非意求的反应都应被考虑为药物不良反应。该术语用于药品是指在药品与不良反应之间的因果关系至少有一个合理的可能性，即不能排除这种关系。

Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).

对已上市药品，ADR指人对用于预防、诊断或治疗疾病或改善生理功能的药物在常用剂量出现的有害和非意求反应（参见ICH临床安全性数据管理指导原则：快速报告的定义和标准）。

1.2 Adverse Event (AE) 不良事件（AE）

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).

在用药病人或临床研究对象中发生的任何不幸医疗事件，他不一定要与治疗有因果关系。因此，一个不良事件（AE）可以是与使用（研究）药物在时间上相关的任何不利的和非意求的征兆（包括异常的实验室发现）、症状或疾病，而不管其是否与药物有关（参见ICH临床安全性数据管理指导原则：快速报告的定义和标准）。

1.3 Amendment (to the protocol) 修改（试验方案）

See Protocol Amendment.

见试验方案修改

1.4 Applicable Regulatory Requirement(s) 适用的管理要求

Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products. 有关实施试验用药品临床试验的任何法律和法规。

1.5 Approval (in relation to Institutional Review Boards) 批准（机构审评委员会）

The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and the applicable regulatory requirements.

IRB表示赞成的决定：指对一项临床试验已经进行审评，并可在IRB、研究机构、GCP和适用管理要

求的约束下由研究机构方实施。

1.6 Audit稽查

A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

对试验相关活动和文件进行系统和独立的监察，以判定试验的实施和数据的记录、分析与报告是否符合试验方案、申办者的标准操作程序（SOP）、临床试验管理规范（GCP）以及适用的管理要求。

1.7 Audit Certificate稽查证书

A declaration of confirmation by the auditor that an audit has taken place.

稽查员确认已进行稽查的声明。

1.8 Audit Report稽查报告

A written evaluation by the sponsor's auditor of the results of the audit. 申办者方稽查关于稽查结果的书面评价

1.9 Audit Trail稽查轨迹

Documentation that allows reconstruction of the course of events. 允许重复出现事件过程的文件。

1.10 Blinding/Masking设盲

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).

一种使试验的一个或几个部分的人员不知道治疗分配的程序。单盲通常指受试者不知道；双盲通常指受试者、研究者、监察员以及在某些情况下数据分析人员也不知道治疗分配。

1.11 Case Report Form (CRF) 病例报告表（CRF）

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

设计用来记录试验方案要求向申办者报告的有关每一例对象的全部信息的印刷的、光学的或电子的文件。

1.12 Clinical Trial/Study 临床试验/研究

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous.

在人类对象进行的任何意在发现或证实一种试验用药品的临床、药理学和/或其他药效学作用；和/或确定一种试验用药品的任何不良反应；和/或研究一种试验用药品的吸收、分布、代谢和排泄，以确定药物的安全性和/或有效性的研究。术语临床试验和临床研究同义。

1.13 Clinical Trial/Study Report 临床试验/研究报告

A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report (see the ICH Guideline for Structure and Content of Clinical Study Reports).

在人类对象进行的任何治疗、预防或诊断剂的试验/研究的书面描述。临床和统计描述、陈述和分析全部列入该单份报告（见ICH临床研究报告的结构和内容指导原则）。

1.14 Comparator (Product) 对照（药物）

An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial. 临床试验中用做对照的试验用药品或市售药物（即阳性对照）或安慰剂。

1.15 Compliance (in relation to trials) 依从性（关于试验的）

Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements.

遵循与试验有关的所有要求、临床试验管理规范（GCP）要求和适用的管理要求。

1.16 Confidentiality 保密性

Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity.

不得向未经授权的个人泄漏申办者所有的资料或对象的身份。

1.17 Contract合同

A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.

在两个或几个有关方之间的一份书面的、有日期和签字的协议，其中陈述了关于工作和责任和分派的安

排，以及关于财务问题的安排。试验方案可以作为合同的基础。

1.18 Coordinating Committee协调委员会

A committee that a sponsor may organize to coordinate the conduct of a multicentre trial. 申办者组织的协调实施多中心试验的委员会。

1.19 Coordinating Investigator协调研究者

An investigator assigned the responsibility for the coordination of investigators at different centres participating in a multicentre trial.

被指定负责协调参加一项多中心试验的各中心研究者工作的一名研究者。

1.20 Contract Research Organization (CRO) 合同研究组织

A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions.

与申办者订立契约完成一个或多个有关申办者方的试验任务和功能的个人或组织（商业性的，学术的或其他）。

1.21 Direct Access 直接访问

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's monitors and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor’s proprietary information. 允许监察、分析、核对和复制任何对于评价临床试验有重要意义的记录和报告。直接访问的任何一方（如国内和国外的管理当局，申办者方的监察员和稽查员）应当受适用管理要求的缺书，采取一切合理的预防措施维护对象身份和申办者资料的保密性。

1.22 Documentation 文件

All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

描述或记录试验的方法、实施和/或结果，影响试验的因素，以及采取的措施等的任何形式的记录（包括但不限于书面、电子、磁性和光学的记录，以及扫描、X射线和心电图）。

1.23 Essential Documents 必需文件

Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced (see 8. Essential Documents for the Conduct of a Clinical Trial).

指各自和合在一起允许评价一个研究的执行情况和所得数据的质量文件（见8.实施临床试验的必需文

件）。

1.24 Good Clinical Practice (GCP) 临床试验管理规范（GCP）

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

是临床试验设计、实施、执行、监察、稽查、记录、分析和报告的标准，它为数据和所报告结果的可信性和准确性提供了保证，并保护试验对象的权利、完整性和机密性。

1.25 Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)

独立的数据监察委员会（IDMC）（数据和安全监察委员会，监察委员会，数据监察委员会）

An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. 由申办者设立一个独立的数据监察委员会，它定期对研究进展、安全性数据和有效性终点进行评估，向申办者建议是否继续、调整或停止试验。

1.26 Impartial Witness 公平的见证人

A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.

独立与临床试验、不受与试验有关人员的不公正影响的个人。如果受试者或受试者的合法接受代表人不能阅读，他/她将参与知情同意过程，并向对象阅读提供给她们的知情同意书和其他书面资料。

1.27 Independent Ethics Committee (IEC) 独立的伦理委员会（IEC）

An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving / providing favourable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects.

一个由医学专业人员和非医学专业人员组成的独立机构（研究机构的、地区的、国家的或超国家的审评机构或委员会），其职责是保证参加试验对象的权益、安全性和健康；并通过对试验方案、研究人员、设

施以及用于获得和记录试验对象知情同意的方法和材料的合理性进行审评和批准/提供起促进作用的意见以对这种保护提供公众保证

The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP as described in this guideline.

在不同的国家，独立的伦理委员会的法律地位、组成、职责、操作和适用的管理要求可能不用，但是应当如本指导原则所述，允许独立的伦理委员会按GCP进行工作。

1.28 Informed Consent 知情同意

A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form.

一个对象在被告知与其作出决定有关的所有试验信息后，资源确认他或她参加一个特定试验的意愿过程。知情同意采用书面的、签字并注明日期的知情同意书。

1.29 Inspection 视察

The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies).

管理当局在试验单位、申办者和/或合同研究组织或管理当局认为何时的其他机构对其认为与临床试验有关的文件、设备、记录和其他资源进行的官方审查的活动。

1.30 Institution (medical) （医学）研究机构

Any public or private entity or agency or medical or dental facility where clinical trials are conducted. 实施临床试验任何或私人的实体、代理机构、医学或齿科设施。

1.31 Institutional Review Board (IRB) 机构审评委员会（IRB）

An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. 由医学、科学和非科学成员组成的一个独立机构，其职责是通过对试验方案及其修订本，获得受试对象

知情同意所用的方法和资料进行审评、批准和继续审评，确保一项试验的受试对象的权利、安全和健康得到保护。

1.32 Interim Clinical Trial/Study Report 临床试验/研究中期报告

A report of intermediate results and their evaluation based on analyses performed during the course of a trial. 根据试验进行过程中所做的分析写出的中期结果和评价的报告

1.33 Investigational Product 试验用药品

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.

一种在临床试验中供试验的或作为对照的活性成分或安慰剂的药物制剂。包括一个已上市药品以不同于所批准的方式适用或组合（制剂或包装），或用于一个未经批准的适应证，或用于收集一个已批准用法的更多资料。

1.34 Investigator 研究者

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. See also Subinvestigator.

负责在一个试验单位实施临床试验的人。如果在一个试验单位是由一组人员实施试验，研究者指这个组的负责人，也称为主要研究者。见次级研究人员。

1.35 Investigator / Institution 研究者/研究机构

An expression meaning \investigator and/or institution, where required by the applicable regulatory requirements\

表示“符合适用管理要求的研究者和/或研究机构”

1.36 Investigator's Brochure 研究者手册

A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects (see 7. Investigator’s Brochure). 与试验药品在人类对象中的研究有关的临床和非临床资料的汇编（见7.研究者手册）

1.37 Legally Acceptable Representative 法律上可接受的代表

An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial.

在适用法律下被授权代表一位未来的受试者同意参加临床试验的个人，或司法人员或其他机关。

1.38 Monitoring 监察

The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

监督一个临床试验的进展，保证临床试验按照试验方案、标准操作程序（SOP）、临床试验管理规范（GCP）和适用的管理要求实施、记录和报告的活动。

1.39 Monitoring Report 监察报告

A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor’s SOPs.

监察员在每一次现场访问和/或其他与试验有关的交流后，根据申办者的SOP写给申办者的书面报告。

1.40 Multicentre Trial 多中心试验

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.

按照一个试验方案，在一个以上试验单位实施，因此由一名以上研究者完成的临床试验。

1.41 Nonclinical Study 非临床试验

Biomedical studies not performed on human subjects. 不是在人类对象进行的生物医学研究。

1.42 Opinion (in relation to Independent Ethics Committee) 意见（与独立的伦理委员会相关）

The judgement and/or the advice provided by an Independent Ethics Committee (IEC).

由独立的伦理委员会（IEC）给出的评价和/或建议

1.43 Original Medical Record 原始医学记录

See Source Documents. 见源文件

1.44 Protocol 试验方案

A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guideline the term protocol refers to protocol and protocol amendments.

一个阐明试验的目的、设计、方法学、统计学考虑和组织的文件。试验方案通常也给出试验的背景和理论基础，但者这可以写在与方案有关的其他参考文件中。在ICH指导原则中，试验方案这一术语指试验方案和方案的修改。

1.45 Protocol Amendment 试验方案的修改

A written description of a change(s) to or formal clarification of a protocol. 对试验方案的改变或澄清的书面描述。

1.46 Quality Assurance (QA) 质量保证（QA）

All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

为保证试验的进行和数据产生、记录以及报告都符合临床试验管理规范（GCP）和适用管理要求所建立的有计划的系统活动。

1.47 Quality Control (QC) 质量控制（QC）

The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled.

在质量保证系统内所采取的操作技术和活动，以查证与试验相关的活动都符合质量要求。

1.48 Randomization 随机化

The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.

为了减少偏倚，采用机遇决定分配的原理将试验对象分配倒治疗组或对照组的过程。

1.49 Regulatory Authorities 管理当局

Bodies having the power to regulate. In the ICH GCP guideline the expression Regulatory Authorities includes the authorities that review submitted clinical data and those that conduct inspections (see 1.29). These bodies are sometimes referred to as competent authorities.

有权进行管理的机构。在ICH GCP指导原则中，管理当局一词包括审评所提交的临床数据和实施视察的机构（见1.29）。这些机构有时指主管当局。

1.50 Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR) 严重不良事件（SAE）或严重药品不良反应

Any untoward medical occurrence that at any dose: 发生在任何剂量的任何不幸医学事件： ? results in death, ? － 导致死亡 ? is life-threatening, ? － 危及生命

? requires inpatient hospitalization or prolongation of existing hospitalization, ? － 需要住院治疗或延长住院时间

results in persistent or significant disability/incapacity, or ? － 导致永久或严重的残疾/能力丧失，或 ? is a congenital anomaly/birth defect ? － 先天性异常/出生缺陷

(see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).

（见ICH临床安全性数据管理指导原则，快速报告的定义和标准）

1.51 Source Data 源数据

All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are

contained in source documents (original records or certified copies).

临床试验中的临床发现、观察或其他活动的原始记录及其可靠副本中的全部资料，他们对于重建和评价试验是必要的。源数据包含在源文件中（原始记录或可靠副本）。

1.52 Source Documents 源文件

Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial).

原始文件、数据和记录（如医院记录，临床和办公室图标，实验室笔记，备忘录，对象日记卡或评价表，药房发药记录，自动仪器的记录数据，在核对后做为准确副本的可靠复印件或抄件，显微胶片，摄影负片，缩微胶卷或磁介质，X线，对象文件，以及保存在药房、实验室和与参与临床试验的医学技术部门中的记录。

1.53 Sponsor 申办者

An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial.

对一个临床试验的发起、管理和/或财务负责的个人、公用、机构或组织。

1.54 Sponsor-Investigator 申办者－研究者

An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator. 单独与其他人一起，发起并实施一个临床试验的个人。在他（们）的直接指示下，给对象服用、发给对象或由对象使用试验药品。该术语并不包括除了个人以外的任何人（如不包括一个公司或一个机构）。一个申办者－研究者的义务包括一个申办者和一个研究者两者的义务。

1.55 Standard Operating Procedures (SOPs) 标准操作程序（SOP）

Detailed, written instructions to achieve uniformity of the performance of a specific function. 为达到均一性完成一个特定职责指定的详细书面说明。

1.56 Subinvestigator 次级研究人员

Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows). See also Investigator.

在一个试验单位，在主要研究者指定和监督下的临床试验组中完成与试验有关的重要程序和/或作出与有关试验的重大决定的成员（如同事，住院医生，特别是研究生）。见研究者。

1.57 Subject/Trial Subject 受试者/试验受试者

An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.

参加一个临床试验作为试验药品的接受者或作为对照的个人。

1.58 Subject Identification Code 对象识别编码

A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in lieu of the subject's name when the investigator reports adverse events and/or other trial related data. 研究者为每一名受试对象指定的独特识别号码，以保护对象的身份并在研究者报告不良事件和/或其他与试验有关数据时代替对象姓名。

1.59 Trial Site 试验单位

The location(s) where trial-related activities are actually conducted. 真正开展与临床试验有关活动的地方。

1.60 Unexpected Adverse Drug Reaction 非预期的药品不良反应

An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).

一种不良反应，其性质或严重程度与现有的产品资料（如一种未批准试验用药品的研究者手册，或包装插入页/一个已经批准药物的产品性能摘要）不符的不良反应（见ICH临床安全性数据管理指导原则：快速报告的定义和标准）。

1.61 Vulnerable Subjects 弱势对象

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

指受到不正当的影响而称为一个临床志愿者的人，他们可能由于期望（无论正当与否）参加试验而伴随的利益，或者拒绝参加会受到等级中资深成员的报复。有等级结构的团体的成员，如医学、药学、齿科或护理专业的学生，附属医院和实验室人员，制药公司的雇员，军人，以及被监禁的人。其他弱势对象包括无可救药的患者，住在福利院利的人，失业者或穷人，处于危急状况的病人，少数民族，无家可归者，流浪者，未成年者，和那些无能力给出知情同意的人

1.62 Well-being (of the trial subjects) 健康（试验对象的）

The physical and mental integrity of the subjects participating in a clinical trial. 参加临床试验对象的体格和精神的完整性。

2. THE PRINCIPLES OF ICH GCP ICH GCP的原则

2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the

Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s). 2.1 临床试验的实施应符合源自赫尔辛基宣言的伦理原则，与ＧＣＰ和适用管理要求一致。

2.2 Before a trial is initiated, for eseeable risks and inconveniences should be weighed against the anticipated

benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks. 2.2 在开始一个试验之前，应当权衡个体试验对象和社会的可预见风险、不方便和预期的受益。只有当预期的受益大于风险时，才开始和继续一个临床试验。

2.3 The rights, safety, and well-being of the trial subjects are the most important considerations and should

prevail over interests of science and society.

2.3 试验对象的权利、安全和健康是最重要的考虑，应当胜过科学和社会的利益。

2.4 The available nonclinical and clinical information on an investigational product should be adequate to

support the proposed clinical trial.

2.4 关于试验用药品可得到的非临床和临床资料应足以支持所提议的临床试验。

2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol. 2.5 临床试验应当有坚实的科学基础，有明确、详细描述的试验方案。

2.6 A trial should be conducted in compliance with the protocol that has received prior institutional review

board (IRB)/independent ethics committee (IEC) approval/favourable opinion.

2.6 临床试验的实施应当遵循事先已经得到研究机构审查委员会（ＩＲＢ）/独立的伦理委员会（ＩＥＣ）批准/赞成的试验方案。

2.7 The medical care given to, and medical decisions made on behalf of, subjects should always be the

responsibility of a qualified physician or, when appropriate, of a qualified dentist. 2.7 一名合格医生或合格牙医的职责永远是给予对象医疗保健，代表对象作出医学决定。

2.8 Each individual involved in conducting a trial should be qualified by education, training, and experience to

perform his or her respective task(s). 2.8 参与实施临床试验个每一个人应当在受教育、培训和经验方面都有资格完成他或她的预期任务。

2.9 Freely given informed consent should be obtained from every subject prior to clinical trial participation. 2.9 应当在参加临床试验前每一个对象获得自由给出的知情同意书。

2.10 All clinical trial information should be recorded, handled, and stored in a way that allows its accurate

reporting, interpretation and verification.

2.10 所有临床试验资料被记录、处理和储存的方式应当允许资料的准确报告、解释和核对。

2.11 The confidentiality of records that could identify subjects should be protected, respecting the privacy and

confidentiality rules in accordance with the applicable regulatory requirement(s). 2.11 可能鉴别对象身份的记录的保密性应当得到保护，依照适用的管理要求尊重隐私和保密规定。

2.12 Investigational products should be manufactured, handled, and stored in accordance with applicable good

manufacturing practice (GMP). They should be used in accordance with the approved protocol.

2.12 试验用药品应当按照适用的药品生产质量管理规范（ＧＭＰ）生产、处理和储存。试验用药品应按照已批准的方案使用。

2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.

2.13 应当建立保证试验各方面质量的程序系统。

研究者应当充分熟悉在试验方案、研究者手册、产品自料以及申办者提供的其他资料中所述的试验用药品的合适用途。

4.1.3 The investigator should be aware of, and should comply with, GCP and the applicable regulatory

requirements.

研究者应当了解并遵循ＧＣＰ和适用的管理要求。

4.1.4 The investigator/institution should permit monitoring and auditing by the sponsor, and inspection by the

appropriate regulatory authority(ies).

研究者/研究机构应当允许申办者的监察和稽查，以及管理部门的视察。

4.1.5 The investigator should maintain a list of appropriately qualified persons to whom the investigator has

delegated significant trial-related duties.

研究者应当有一份合适资格、并已委派给他们与试验相关的和总要任务的人员名单。

4.2 Adequate Resources 足够的资源

4.2.1 The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for

recruiting the required number of suitable subjects within the agreed recruitment period.

研究者应能证明（如根据遗忘的数据）在协议的招募期内接纳所需要数目的合适对象的可能性。 4.2.2 The investigator should have sufficient time to properly conduct and complete the trial within the agreed

trial period.

研究者在协议的试验期内应当有足够的时间实施和完成试验。

4.2.3 The investigator should have available an adequate number of qualified staff and adequate facilities for

the foreseen duration of the trial to conduct the trial properly and safely.

在可预见的试验期内，研究者应当有足够数量的合格职员和充足的设备来争取、安全的实施试验。 4.2.4 The investigator should ensure that all persons assisting with the trial are adequately informed about the

protocol, the investigational product(s), and their trial-related duties and functions.

研究者应当保证所有的试验辅助人员已充等了解试验方案，试验用药品，及他们与试验相关的责任和职能。

4.3 Medical Care of Trial Subjects 试验对象的医疗

4.3.1 A qualified physician (or dentist, when appropriate), who is an investigator or a sub-investigator for the

trial, should be responsible for all trial-related medical (or dental) decisions.

作为一名研究者或次级研究人员的合格医生（或牙医）应当对与试验有关的所有医学（牙科）决定负责。

4.3.2 During and following a subject's participation in a trial, the investigator/institution should ensure that

adequate medical care is provided to a subject for any adverse events, including clinically significant

laboratory values, related to the trial. The investigator/institution should inform a subject when medical care is needed for intercurrent illness(es) of which the investigator becomes aware.

在对象参加一个试验期间或以后，研究者/研究机构应当保证为对象的任何不良反应，包括与试验有关的临床上有意义的实验室测定值提供合宜的医疗保健。研究者知道并发疾病需要医疗保健时，研究者/研究机构应当通知对象。

4.3.3 It is recommended that the investigator inform the subject's primary physician about the subject's

participation in the trial if the subject has a primary physician and if the subject agrees to the primary physician being informed.

如果对象有初级医生并且对象同意让初级医生知道，建议研究者将对象参加试验的事通知对象的初级医生。

4.3.4 Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, the

investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the subject's rights.

尽管一名对象没有义务给出他/她中途退出试验的理由，研究者仍应当在充分尊重对象权利的同时作出合理的努力确认其退出理由。

4.4 Communication with IRB/IEC 与IRB/IEC的交流

4.4.1 Before initiating a trial, the investigator/institution should have written and dated approval/favourable

opinion from the IRB/IEC for the trial protocol, written informed consent form, consent form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided to subjects.

在开始一个试验前，研究者/研究机构应当有IRB/IEC对试验方案、知情同意书、知情同意书的更新、对象招募程序（如广告）、以及提供给对象的任何其他书面资料的书面的、注明日期的批准/赞成意见。

4.4.2 As part of the investigator's/institution’s written application to the IRB/IEC, the investigator/institution

should provide the IRB/IEC with a current copy of the Investigator's Brochure. If the Investigator's Brochure is updated during the trial, the investigator/institution should supply a copy of the updated Investigator’s Brochure to the IRB/IEC.

作为研究者/研究机构向IRB/IEC书面申请的一部分，研究者/研究机构应当向IRB/IEC提供研究者手册的当前文本。如果研究者手册在试验中更新，研究者/研究机构应当向IRB/IEC提供更新的研究者手册。

4.4.3 During the trial the investigator/institution should provide to the IRB/IEC all documents subject to review.

在试验期间，研究者/研究机构应当向IRB/IEC提供全部供审评的文件。

4.5 Compliance with Protocol 对试验方案的依从性

4.5.1 The investigator/institution should conduct the trial in compliance with the protocol agreed to by the

sponsor and, if required, by the regulatory authority(ies) and which was given approval/favourable

opinion by the IRB/IEC. The investigator/institution and the sponsor should sign the protocol, or an alternative contract, to confirm agreement.

研究者/研究机构应当按照申办者和（如有必要）管理当局同意、并得到IRB/IEC批准/赞成的方案实施试验。研究者/研究机构和申办者应当在方案上或另立的合同上签字，确认同意方案。

4.5.2 The investigator should not implement any deviation from, or changes of the protocol without

agreement by the sponsor and prior review and documented approval/favourable opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)).

研究者在没有取得申办者同意和事先得到IRB/IEC对于一个修改的审评与书面批准/赞成时，不应当偏离或改变方案，除非必需消除试验对象的直接危险或这些改变只涉及试验的供应或管理方面（如更换监察员，改变电话号码）。 4.5.3 The investigator, or person designated by the investigator, should document and explain any deviation from the approved protocol.

研究者，或由研究者指定的人，应当记录和解释已批准方案的任何偏离。

4.5.4 The investigator may implement a deviation from, or a change of, the protocol to eliminate an immediate

hazard(s) to trial subjects without prior IRB/IEC approval/favourable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted:

为了消除对试验对象的直接危险，研究者可以没有IRB/IEC的预先批准/赞成意见偏离或改变方案。所实施的偏离或改变、改变的理由、以及所提议的方案修改尽可能地提交给： a) to the IRB/IEC for review and approval/favourable opinion,

IRB/IEC审评并得到批准/赞成

b) to the sponsor for agreement and, if required, 申办者征得同意和，如果需要 c) to the regulatory authority(ies). 管理当局

4.6 Investigational Product(s) 试验药品

4.6.1 Responsibility for investigational product(s) accountability at the trial site(s) rests with the

investigator/institution.

在试验单位，试验用药品计数地责任归于研究者/研究机构。

4.6.2 Where allowed/required, the investigator/institution may/should assign some or all of the

investigator's/institution’s duties for investigational product(s) accountability at the trial site(s) to an appropriate pharmacist or another appropriate individual who is under the supervision of the investigator/institution..

只要允许/需要，研究者/研究机构可以/应当将试验单位研究者地/机构对试验用药品计数的责任部分或全部指派给在研究者/研究机构监督下的合适的药师或其他适当的人员。

4.6.3 The investigator/institution and/or a pharmacist or other appropriate individual, who is designated by

the investigator/institution, should maintain records of the product's delivery to the trial site, the inventory at the site, the use by each subject, and the return to the sponsor or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the investigational product(s) and trial subjects. Investigators should maintain records that document adequately that the subjects were provided the doses specified by the protocol and reconcile all investigational product(s) received from the sponsor.

研究者/研究机构和/或受研究者/研究机构指派的一名药师或其他合适的个人，应当保 存试验用药品交到试验单位的记录，在试验单位的存货清单，每位对象的使用记录，和未使 用的药品交还给申办者或另法处置的记录。这些记录应包含日期、数量、批号/系列号、时效期（如有）、和分配给试验用药品和试验对象的特别编码。研究者应保持记载有按方案说 明给予对象药量的记录，并应与从申办者处收到的试验用药品总数一致。

4.6.4 The investigational product(s) should be stored as specified by the sponsor (see 5.13.2 and 5.14.3) and in

accordance with applicable regulatory requirement(s).

试验用药品应按申办者的说明储存（见5.13.2和5.14.3）并符合适用的管理要求。

4.6.5 The investigator should ensure that the investigational product(s) are used only in accordance with the

approved protocol.

研究者应当保证试验用药品只按已批准的方案使用。

4.6.6 The investigator, or a person designated by the investigator/institution, should explain the correct use of

the investigational product(s) to each subject and should check, at intervals appropriate for the trial, that each subject is following the instructions properly.

研究者或研究者/研究机构指定的人，应当向每一位对象解释试验用药品的娥正确用法，并应在适合于该试验的一定间隔检查每一位对象完全遵照使用说明用药。

4.7 Randomization Procedures and Unblinding 随机程序和揭盲

The investigator should follow the trial's randomization procedures, if any, and should ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product(s).

研究者应当遵循试验的随机化程序（如果有），并应保证依照方案打开随机号码。如果试验采用盲法，研究者应当立即记录并向申办者解释试验用药品的任何提前破盲（如以外破盲，因严重不良事件破盲）。

4.8 Informed Consent of Trial Subjects 试验对象的知情同意

4.8.1 In obtaining and documenting informed consent, the investigator should comply with the applicable

regulatory requirement(s), and should adhere to GCP and to the ethical principles that have their origin in

the Declaration of Helsinki. Prior to the beginning of the trial, the investigator should have the IRB/IEC's written approval/favourable opinion of the written informed consent form and any other written information to be provided to subjects.

在获得和证明知情同意过程中，研究者应当遵循适用的管理规定，应当符合ＧＣＰ和源自赫尔辛基年宣言的伦理原则。在开始试验前，研究者应当有IRB/IEC对于书面的知情同意书和提供给对象的其他文字资料的书面批准/赞成意见。

4.8.2 The written informed consent form and any other written information to be provided to subjects should

be revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised written informed consent form, and written information should receive the IRB/IEC's approval/favourable opinion in advance of use. The subject or the subject’s legally acceptable representative should be informed in a timely manner if new information becomes available that may be relevant to the subject’s willingness to continue participation in the trial. The communication of this information should be documented.

无论何时得到与对象的知情同意可能相关的新的资料后，提供给对象的书面知情同意书和其他文字资料都应当进行修改。修改后的书面知情同意书和其他文字资料在适用前都应当得到IRB/IEC的批准/赞成。如果有与对象继续参加试验的愿望可能相关的新资料，应及时通知对象和对象的合法可接受代表。这种资料的交流应当被记录下来。

4.8.3 Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or

to continue to participate in a trial.

无论试验就人员还是试验职员，都不应强迫或不正当地影响一个对象参加或继续参加一个试验。 4.8.4 None of the oral and written information concerning the trial, including the written informed consent

form, should contain any language that causes the subject or the subject's legally acceptable representative to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence.

关于试验的口述或书面的资料，包括书面的知情同意书，都不应包含会引起对象或对象的合法可接受代表放弃或看来象是放弃任何合法利益的语言；或者免除或看来象是免除研究者、机构、申办者或他们的代理由于疏忽应负责任的语言。

4.8.5 The investigator, or a person designated by the investigator, should fully inform the subject or, if the

subject is unable to provide informed consent, the subject's legally acceptable representative, of all pertinent aspects of the trial including the written information and the approval/ favourable opinion by the IRB/IEC.

研究者或由研究者指定的人，至少应当告诉对象，或如果对象不能提供知情同意时告诉对象的合法可接受的代表，所有与试验相关的方面，包括文字资料和IRB/IEC的批准/赞成意见。

4.8.6 The language used in the oral and written information about the trial, including the written informed

consent form, should be as non-technical as practical and should be understandable to the subject or the subject's legally acceptable representative and the impartial witness, where applicable.

关于试验的口述和书面资料，包括书面知情同意书，所用的语言应当是非技术术语性的实用语言，对于对象或对象的合法可接受代表或公正的见证人应当是易懂的。

d) The trial procedures to be followed, including all invasive procedures. 试验就行的程序，包括所有侵袭性程序

e) The subject's responsibilities. 对象的责任

f) Those aspects of the trial that are experimental. 试验的实验方面性

g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or nursing infant. 带给对象、可能时带给胚胎、胎儿或哺乳婴儿的合理预见的危险或不方便。

h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be made aware of this. 可合理预见的受益。不存在预期的临床受益时，对象应当知道这一点。

i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks. 对象可能得到的可替代治疗程序或过程，以及这些治疗的重要潜在受益和风险。 j) The compensation and/or treatment available to the subject in the event of trial-related injury. 在与试验相关的伤害事件中对象可获得的补偿和/治疗。

k) The anticipated prorated payment, if any, to the subject for participating in the trial. 给参加试验对象的预期按比例分配的支付（如果有）

l) The anticipated expenses, if any, to the subject for participating in the trial. 对象因参加试验的预期花费（如果有）

m) That the subject's participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled. 对象参加试验是自愿的，对象可以拒绝参加试验，或在任何时候退出试验而不会收到出发或损失本来对象有权利得到的利益。

n) That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be granted direct access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject's legally acceptable representative is authorizing such access. 监察员、稽查员、IRB/IEC和管理当局将被准予在不违反对象的保密性、在适用法律与规定准许的程度直接访问对象的原始医学记录以查证临床试验程序和/或数据，对象或对象的合法可接受的代表通过签署书面的知情同意书授权这种访问。

o) That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the subject’s identity will remain confidential.

在适用法律和/或规定允许的范围，能鉴别对象的记录应保密，不得公开这些记录。如果试验结果发表，对象鉴别仍然是保密的。

p) That the subject or the subject's legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the subject's willingness to continue participation in the trial. 如果得到与对象继续参加试验的愿望可能相关的资料，对象或对象的合法可接受代表将得到及时通报。

q) The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to contact in the event of trial-related injury. 需要进一步了解有关试验资料和试验对象的权利时的联系人，以及在发生与试验有关的伤害时的联系人。

r) The foreseeable circumstances and/or reasons under which the subject's participation in the trial may be terminated. 对象参加试验可能被终止的可预见情况和/或理由

s) The expected duration of the subject's participation in the trial. 对象参加试验的预期持续时间

t) The approximate number of subjects involved in the trial. 参加试验对象的大约人数

4.8.11 Prior to participation in the trial, the subject or the subject's legally acceptable representative should

receive a copy of the signed and dated written informed consent form and any other written information provided to the subjects. During a subject's participation in the trial, the subject or the subject’s legally acceptable representative should receive a copy of the signed and dated consent form updates and a copy of any amendments to the written information provided to subjects.

在参加试验前，对象或对象的合法可接受代表应收到一份已签署并注明日期的书面知情同意书的复印件和其他提供给对象的书面资料。对象参加试验期间，对象或对象的合法可接受代表应收到已签署并注明日期的知情同意书的更新的复印件和提供给对象的书面资料的修改文本。

4.8.12 When a clinical trial (therapeutic or non-therapeutic) includes subjects who can only be enrolled in the

trial with the consent of the subject’s legally acceptable representative (e.g., minors, or patients with severe dementia), the subject should be informed about the trial to the extent compatible with the subject’s understanding and, if capable, the subject should sign and personally date the written informed consent.

当一个临床试验（治疗的或非治疗的）包括那些职能由其合法可接受代表表示进入试验的对象时（如未成年人，或严重痴呆病人），应当在对象能理解的程度告知对象关于试验的信息。如果可能，对象应当亲自签署书面的知情同意并注明日期。

4.8.13 Except as described in 4.8.14, a non-therapeutic trial (i.e. a trial in which there is no anticipated direct

clinical benefit to the subject), should be conducted in subjects who personally give consent and who sign and date the written informed consent form.

除非如4.8.14所描述的情况外，一个非治疗试验（如对于对象没有可预期的直接临床好处的试验）应当在那些亲自同意并在书面的知情同意书上签字和注明日期的对象中进行。

4.8.14 Non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative

provided the following conditions are fulfilled:

只要符合下列条件，非治疗试验可以在由合法可接受代表同意的对象中进行：

a) The objectives of the trial can not be met by means of a trial in subjects who can give informed consent personally. 试验的目的不能通过在能亲自给出知情同意的对象中进行的试验达到。 b) The foreseeable risks to the subjects are low. 对象的可预见风险很低

c) The negative impact on the subject’s well-being is minimized and low. 对于对象健康的负面影响被减到最小，并且是最低的 d) The trial is not prohibited by law. 法律不禁止该试验

e) The approval/favourable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the written approval/ favourable opinion covers this aspect.

明确的寻求IRB/IEC对接纳这些对象的批准/赞成意见；书面的批准/赞成意见同意接纳这些对象。 Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended. Subjects in these trials should be particularly closely monitored and should be withdrawn if they appear to be unduly distressed.

除非被证明是一个例外，这类试验应当在具有预期适用试验用药品的疾病或状况的病人中进行。这些试验中对象应当受到特别的密切检查，如果他们显得过分痛苦，应当退出试验。

4.8.15 In emergency situations, when prior consent of the subject is not possible, the consent of the subject's

legally acceptable representative, if present, should be requested. When prior consent of the subject is not possible, and the subject’s legally acceptable representative is not available, enrolment of the subject should require measures described in the protocol and/or elsewhere, with documented approval/favourable opinion by the IRB/IEC, to protect the rights, safety and well-being of the subject and to ensure compliance with applicable regulatory requirements. The subject or the subject's legally acceptable representative should be informed about the trial as soon as possible and consent to continue and other consent as appropriate (see 4.8.10) should be requested.

在紧急情况下，不可能事先得到对象的知情同意时，应该请求对象的合法可接受代表（如果在场）的同意。当对象的接纳需要按方案和/或其他文件中描述的、得到IRB/IEC的书面批 准/赞成意见的方法进行，以保护对象的权利、安全和健康，并保证依从适用的管理要求。应尽可能地通知对象或

对象地合法可接受代表关于试验地事，并应得到他们继续参加试验和 其他事项（见4.8.10）的知情同意。

4.9 Records and Reports 记录和报告

4.9.1 The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported

to the sponsor in the CRFs and in all required reports.

研究者应当保证给申办者的病历报告表（ＣＲＦ）和所有需要的报告中的数据的准确性、完整性、易辩性和及时性。

4.9.2 Data reported on the CRF, that are derived from source documents, should be consistent with the source

documents or the discrepancies should be explained.

ＣＲＦ中来自源文件的数据应当与源文件一致，如由不一致应作出解释。

4.9.3 Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and should not

obscure the original entry (i.e. an audit trail should be maintained); this applies to both written and electronic changes or corrections (see 5.18.4 (n)). Sponsors should provide guidance to investigators and/or the investigators' designated representatives on making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator. The investigator should retain records of the changes and corrections.

ＣＲＦ中数据的任何改变或变更，应当注明日期、姓名首字母和说明（如有必要），并应当使原来的记录依然可见（即应保留核查痕迹）；这同样适用于文字和电子的改变或更正（见5.18.4（ｎ））。申办者应当向研究者和/或研究者指定的代表提供关于进行这种更正的指南。申办者应当有书面的程序以保证在CRF中由申办者指定的代表作出的改变或更正是有记录的、有必要的，并得到研究者的认可。研究者应当保留改变和更正的记录。

4.9.4 The investigator/institution should maintain the trial documents as specified in Essential Documents for

the Conduct of a Clinical Trial (see 8.) and as required by the applicable regulatory requirement(s). The investigator/institution should take measures to prevent accidental or premature destruction of these documents.

研究者/研究机构应当按《实施临床试验的基本文件》（见8.）所述和适用管理要求保存试验文件。研究者/研究机构应当采取措施防止这些文件的以外或过早破坏。

4.9.5 Essential documents should be retained until at least 2 years after the last approval of a marketing

application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained (see 5.5.12).

基本文件应当保留到最后批准在一个ＩＣＨ地区上市后至少2年，和直到最后在一个ＩＣＨ地区没有未决的或仍在考虑的上市应用，或试验用药品的临床研究正式停止后至少已过去2年。但是，如

申办者在得到全部多需要文件（如IRB/IEC和管理当局的批准/赞成意见）之前不得向研究者/研究机构提供试验药物。

5.14.3 The sponsor should ensure that written procedures include instructions that the investigator/institution

should follow for the handling and storage of investigational product(s) for the trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from subjects, and return of unused investigational product(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)).

申办者应当确保书面操作程序包含研究者/研究机构应当遵循的关于试验用药品的处理和储存的说明及其文件。程序应当说明适当和安全的接受、处理、储存、分发、从对象处取回未使用的药物以及将未使用的试验用药品返回给申办者（或经申办者授权并遵照适用管理要求销毁）。 5.14.4 The sponsor should:

申办者应当：

a) Ensure timely delivery of investigational product(s) to the investigator(s). 确保按时将试验用药品送达研究者

b) Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational product(s) (see 8. Essential Documents for the Conduct of a Clinical Trial). 保存证明运输、接收、分发、收回和销毁试验用药品的记录（见8.实施临床试验的基本文件） c) Maintain a system for retrieving investigational products and documenting this retrieval (e.g. for deficient product recall, reclaim after trial completion, expired product reclaim). 有一个取回试验用药品和记录取回的规定（如有缺陷产品的收回，在试验结束后归还，过期药品归还）。 d) Maintain a system for the disposition of unused investigational product(s) and for the documentation of this disposition. 有一个处置未使用研究药品和记录这种处置的规定。

5.14.5 The sponsor should: 申办者应当

a) Take steps to ensure that the investigational product(s) are stable over the period of use.

采取步骤以保证试验药品在整个使用期内的稳定性。

b) Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period. 维持足够数量的用于试验中的试验用药品，以在万一有必要时再确认其规格，并保存批样分析和特性记录。只要产品稳定性许可，样品应当被保留到试验数据分析完成或适用管理要求的需要时间，取两者中较长的期限。

5.15 Record Access 记录访问

5.15.1 The sponsor should ensure that it is specified in the protocol or other written agreement that the

investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits, IRB/IEC review, and regulatory inspection.

申办者应当确保在方按中或其他书面协议中已经说明，研究者/研究机构应允许试验有关的监察员、稽查员、IRB/IEC审评和管理部门视察直接访问原始数据。

5.15.2 The sponsor should verify that each subject has consented, in writing, to direct access to his/her original

medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection.

申办者应当核实，每一例对象已经书面同意，在进行鱼试验相关的检查、稽查、IRB/IEC审评和管理部门视察时直接访问他/她的原始医学记录

5.16 Safety Information 安全性资料

5.16.1 The sponsor is responsible for the ongoing safety evaluation of the investigational product(s).

申办者负责试验用药品正在进行的安全性评价。

5.16.2 The sponsor should promptly notify all concerned investigator(s)/institution(s) and the regulatory

authority(ies) of findings that could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's approval/favourable opinion to continue the trial.

申办者应当立即通知所有有关研究者/研究机构和管理当局关于可能对对象的安全性有不良影响、 影响试验实施的或改变IRB/IEC对继续试验的批准/赞成的发现。

5.17 Adverse Drug Reaction Reporting 药品不良反应报告

5.17.1 The sponsor should expedite the reporting to all concerned investigator(s)/institutions(s), to the

IRB(s)/IEC(s), where required, and to the regulatory authority(ies) of all adverse drug reactions (ADRs) that are both serious and unexpected.

申办者应当迅速向所有有关研究者/研究机构、有关的IRB/IEC、管理当局报告所有严重的和非预期的药品不良反应。

5.17.2 Such expedited reports should comply with the applicable regulatory requirement(s) and with the ICH

Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.

这种快速报告应当符合适用管理要求和《ＩＣＨ临床安全性数据管理指导原则：快速报告的定义和标准》

5.17.3 The sponsor should submit to the regulatory authority(ies) all safety updates and periodic reports, as

required by applicable regulatory requirement(s).

申办者应当根据使用管理要求向管理当局提交全部安全性更新和定期报告。

5.18 Monitoring 监查

5.18.1 Purpose 目的

The purposes of trial monitoring are to verify that:

试验监查的目的是核实

a) The rights and well-being of human subjects are protected. 对象的权利和健康得到保护

b) The reported trial data are accurate, complete, and verifiable from source documents. 所报告的试验数据是准确和完整的，并能从原始文件得到证实。

c) The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s). 试验的实施符合最近批准的方按/方按修改，符合ＧＣＰ和适用管理要求

5.18.2 Selection and Qualifications of Monitors

选择合格的监查员

a) Monitors should be appointed by the sponsor. 监察员应当由申办者指定

b) Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately. A monitor’s qualifications should be documented. 监察员应当受过核实的培训，应当有足够的监察试验的科学/活临床知识。监察员的资格应当有文件证明。

c) Monitors should be thoroughly familiar with the investigational product(s), the protocol, written informed consent form and any other written information to be provided to subjects, the sponsor’s SOPs, GCP, and the applicable regulatory requirement(s). 监察员应当透彻了解试验用药品、研究方按、知情同意书和其他提供给对象的书面资料、申办者的各种ＳＯＰ、ＧＣＰ和适用管理要求。

5.18.3 Extent and Nature of Monitoring 监查的范围和性质

The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate extent and nature of monitoring. The determination of the xtent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial. In general there is a need for on-site monitoring, before, during, and after the trial; however in exceptional circumstances the sponsor may determine that central monitoring in conjunction with procedures such as investigators’ training and meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified.

申办者应当保证试验得到适当的监察。申办者应当决定监察的合适范围和性质。监察的范围和性质应当根据目标、目的、设计、复杂性、盲法、样本大小和试验终点确定。通常需要在试验前、试验期间和试验后进行现场监察，但是在特别的场合，申办者可以决定与某些步骤，如研究人员培训和研究人员会议，合在一起的终点监察。多方面的书面指导原则可以保证恰当地按照ＧＣＰ实施试验。统计学上控制地抽样可能是一个可以接受地选择需要核对的数据的方法。 5.18.4 Monitor's Responsibilities 监查员的责任

The monitor(s) in accordance with the sponsor’s requirements should ensure that the trial is conducted and documented properly by carrying out the following activities when relevant and necessary to the trial and the trial site:

按照申办者的要求，在对试验和试验单位恰当和必要时，监察员应当通过下列活动保证试验被正确的实施和记录：

a) Acting as the main line of communication between the sponsor and the investigator. 在申办者和研究者之间的交流起干线作用。

b) Verifying that the investigator has adequate qualifications and resources (see 4.1, 4.2, 5.6) and remain adequate throughout the trial period, that facilities, including laboratories, equipment, and staff, are adequate to safely and properly conduct the trial and remain adequate throughout the trial period. 验证研究者有足够的资格和自愿（见4.1，4.2，5.6），并且在整个试验期间仍然是足够的；设备，包括实验室、仪器和职员足以安全和正确地实施试验，并在整个试验期间也是足够地。 c) Verifying, for the investigational product(s): 对于试验用药品，核实：

i) That storage times and conditions are acceptable, and that supplies are sufficient throughout the trial. 储存时间和条件是可以接受的，在整个试验中供应充足

ii) That the investigational product(s) are supplied only to subjects who are eligible to receive it and at the protocol specified dose(s). 试验用药品只按试验方案规定地剂量提供给合格地对象

iii) That subjects are provided with necessary instruction on properly using, handling, storing, and returning the investigational product(s). 向对象提供正确使用、处理、储存和归还试验用药品地说明

iv) That the receipt, use, and return of the investigational product(s) at the trial sites are controlled and documented adequately. 在试验单位，试验用药品接收、使用和归还试验用药品地说明

v) That the disposition of unused investigational product(s) at the trial sites complies with applicable regulatory requirement(s) and is in accordance with the sponsor.

试验单位对未使用地试验用药品地处置符合管理要求和申办者地要求。

d) Verifying that the investigator follows the approved protocol and all approved amendment(s), if any. 核实研究者遵循已批准地方案和所有已批准的修改

e) Verifying that written informed consent was obtained before each subject's participation in the trial. 核实在每个研究对象参加试验前已经得到书面的知情同意

f) Ensuring that the investigator receives the current Investigator's Brochure, all documents, and all trial supplies needed to conduct the trial properly and to comply with the applicable regulatory requirement(s). 确保研究者收到最近的研究者手册、所有的文件和按照适用管理要求正确实施试验必需的所有试验用品。

g) Ensuring that the investigator and the investigator's trial staff are adequately informed about the trial. 保证研究者及其试验职员对试验有充分的知识

h) Verifying that the investigator and the investigator's trial staff are performing the specified trial functions, in accordance with the protocol and any other written agreement between the sponsor and the investigator/institution, and have not delegated these functions to unauthorized individuals. 核实研究者及其试验职员正在按照方案和申办者与研究者/研究机构之间的其他书面协议执行特定的试验职责，没有将这些职责委派给未经授权的人。 i) Verifying that the investigator is enrolling only eligible subjects. 核实研究者只招募合格的对象 j) Reporting the subject recruitment rate. 报告对象招募速度

k) Verifying that source documents and other trial records are accurate, complete, kept up-to-date and maintained. 核实源文件和其他试验记录是准确的、完整的、保持更新并都保存着

l) Verifying that the investigator provides all the required reports, notifications, applications, and submissions, and that these documents are accurate, complete, timely, legible, dated, and identify the trial. 确保研究者提供所有需要的报告、通知、申请和递交的文件，并且这些文件都是准确、完整、按时、清晰易读、注明日期和试验鉴别

m) Checking the accuracy and completeness of the CRF entries, source documents and other trial-related records against each other. The monitor specifically should verify that: 彼此对照检查ＣＲＦ记录、源文件和其他试验有感记录的准确系国内和完整性。监察员尤其应当检查：

i) The data required by the protocol are reported accurately on the CRFs and are consistent with the

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