INTERNATIONAL STANDARD 国际标准 ISO 14155

Third edition 第三版 2020-07

 

Clinical investigation of medical devices for human subjects — Good clinical practice

 

人类受试者的医疗器械临床研究——良好的临床实践

 

Investigation clinique des dispositifs médicaux pour sujets humains — Bonne pratique clinique

 

Contents目录

Foreword前言

 

Clinical investigation of medical devices for human subjects — Good clinical practice人类受试者的医疗器械临床研究-良好的临床实践

 

1. Scope范围

 

2. Normative references引用标准

 

3. Terms and definitions术语和定义

 

4. Summary of good clinical practice (GCP) principles良好临床实践(GCP)原则概述

 

5. Ethical considerations伦理考虑

 

5.1. General概述

 

5.2. Improper influence or inducement不当影响或诱导

 

5.3. Compensation and additional health care补偿和额外的医疗保健

 

5.4. Registration in publicly accessible database在公共可访问数据库中注册

 

5.5. Responsibilities责任

 

5.6. Communication with the ethics committee (EC)与伦理委员会的沟通

 

5.7. Vulnerable populations弱势人群

 

5.8. Informed consent知情同意

 

6. Clinical investigation planning临床研究计划

 

6.1. General概述

 

6.2. Risk management风险管理

 

6.3. Justification for the design of the clinical investigation临床研究设计的合理性

 

6.4. Clinical investigation plan (CIP)临床研究计划

 

6.5. Investigator's brochure (IB)研究者手册

 

6.6. Case report forms (CRFs)病例报告表

 

6.7. Monitoring plan监查计划

 

6.8. Investigation site selection研究中心选择

 

6.9. Agreement(s)协议

 

6.10. Labelling标签

 

6.11. Data monitoring committee (DMC)数据监查委员会

 

7. Clinical investigation conduct临床研究实施

 

7.1. General概述

 

7.2. Investigation site initiation研究中心启动

 

7.3. Investigation site monitoring

 

7.4. Adverse events and device deficiencies不良事件和器械缺陷

 

7.5. Clinical investigation documents and documentation临床研究文件和文档

 

7.6. Additional members of the investigation site team研究中心小组的额外成员

 

7.7. Subject privacy and confidentiality of data受试者隐私和数据保密

 

7.8. Document and data control文件和数据控制

 

7.9. Investigational device accountability研究器械管理

 

7.10. Accounting for subjects受试者审查

 

7.11. Auditing稽查

 

8. Suspension, termination, and close-out of the clinical investigation暂停、终止和结束临床研究

 

8.1. Completion of the clinical investigation完成临床试验

 

8.2. Suspension or premature termination of the clinical investigation暂停或提前终止临床研究

 

8.3. Routine close-out常规关中心

 

8.4. Clinical investigation report临床研究报告

 

8.5. Risk assessment and conclusions风险评估和结论

 

8.6. Document retention文件保存

 

9. Responsibilities of the sponsor申办者的职责

 

9.1. Clinical quality management临床质量管

 

9.2. Clinical investigation planning and conduct临床研究的计划和实施

 

9.3. Outsourcing of duties and functions职责和职能的外包

 

9.4. Communication with regulatory authorities与监管机构沟通

 

10. Responsibilities of the principal investigator主要研究者的职责

 

10.1. General概述

 

10.2. Qualification of the principal investigator主要研究者的资格

 

10.3. Qualification of investigation site研究中心的资格

 

10.4. Communication with the EC与伦理委员会沟通

 

10.5. Informed consent process知情同意过程

 

10.6. Compliance with the CIP研究方案的依从性

 

10.7. Medical care of subjects受试者的医疗保健

 

10.8. Safety reporting安全性报告

 

Annex A Clinical investigation plan (CIP) 附件A临床研究计划

 

A.1. General概述

 

A.1.1. Introduction介绍

 

A.1.2. Identification of the clinical investigation plan临床研究计划的识别信息

 

A.1.3. Sponsor申办者

 

A.1.4. Principal investigator, coordinating investigator and investigation site(s)主要研究者，协调研究员和研究中心

 

A.1.5. Overall synopsis of the clinical investigation临床研究的总体摘要

 

A.2. Identification and description of the investigational device研究器械的识别和描述

 

A.3. Justification for the design of the clinical investigation临床研究设计的合理性

 

A.4. Benefits and risks of the investigational device, clinical procedure, and clinical investigation试验器械、临床流程和临床研究的受益和风险

 

A.5. Objectives and hypotheses of the clinical investigation临床研究的目的和假设

 

A.6. Design of the clinical investigation临床研究设计

 

A.6.1. General概述

 

A.6.2. Investigational device(s) and comparator(s)研究器械和对照产品

 

A.6.3. Subjects受试者

 

A.6.4. Procedures流程

 

A.6.5. Monitoring plan监查计划

 

A.7. Statistical design and analysis统计设计和计划

 

A.8. Data management数据管理

 

A.9. Amendments to the CIP临床研究计划的修订

 

A.10. Deviations from clinical investigation plan临床研究计划的偏离

 

A.11. Device accountability器械管理

 

A.12. Statements of compliance合规性声明

 

A.13. Informed consent process知情同意过程

 

A.14. Adverse events, adverse device effects, and device deficiencies不良事件、器械不良反应和器械缺陷

 

A.15. Vulnerable population (if applicable)弱势人群（如适用）

 

A.16. Suspension or premature termination of the clinical investigation暂停或提前中止临床研究

 

A.17. Publication policy出版政策

 

A.18. Bibliography参考文献

 

Annex B Investigator's brochure 附件B (IB)研究者手册

 

B.1. General概述

 

B.1.1. Introduction介绍

 

B.1.2. Identification of the IB研究者手册的识别信息

 

B.1.3. Sponsor/manufacturer申办者/制造商

 

B.2. Investigational device information研究器械信息

 

B.3. Preclinical testing临床前测试

 

B.4. Existing clinical data现有的临床数据

 

B.5. Risk management of the investigational device研究器械的风险管理

 

B.6. Regulatory and other references法规和其他参考

 

Annex C Case report forms (CRFs) 附件C 病例报告表

 

C.1 General概述105

 

C.2 Content and format内容与格式

 

C.2.1 Overall considerations总体考虑

 

C.2.2 Cover page/login screen封面/登录界面

 

C.2.3 Header or footer/e-CRF identifier页眉或页脚/电子病例报告表的标识符

 

C.2.4 Types of CRF病例报告表形式

 

C.3 Procedural issues发布流程

 

Annex D Clinical investigation report 附件D 临床研究报告

 

D.1 General概述

 

D.2 Cover page封面

 

D.3 Table of contents目录内容

 

D.4 Summary概要

 

D.5 Introduction介绍

 

D.6 Investigational device and methods研究器械和方法

 

D.6.1 Investigational device description研究器械描述

 

D.6.2 Clinical investigation plan (CIP)临床研究计划

 

D.7 Results结果

 

D.8 Discussion and overall conclusions讨论与结论

 

D.9 Abbreviated terms and definitions缩写的术语和定义

 

D.10 Ethics伦理

 

D.11 Investigators and administrative structure of clinical investigation临床研究的研究者和管理结构

 

D.12 Signature page签单页

 

D.13 Annexes to the report报告附件

 

Annex E Essential clinical investigation documents 附件E 临床研究基本文件

 

Annex F Adverse event categorization 附件F 不良事件分类

 

Annex G EC responsibilities 附件G伦理委员会职责

 

G.1 General概述

 

G.2 Responsibilities职责

 

G.3 Composition, functions, and operations组成、功能和实施

 

G.4 Information needed所需信息

 

G.5 Procedures流程

 

G.6 EC approval/favourable opinion letters伦理委员会批准/赞同意见函

 

G.7 Records记录

 

Annex H Application of ISO 14971 to clinical investigations  附件H ISO14971在临床研究中的应用

 

Annex I Clinical development stages 附件I 临床研发阶段

 

I.1 Background背景

 

I.2 Regulatory status监管状态

 

I.2.1 General概述

 

I.2.2 Pre-market clinical investigation上市前临床研究

 

I.2.3 Post-market clinical investigation上市后临床研究

 

I.3 Clinical development stages临床研究阶段

 

I.3.1 General概述

 

I.3.2 Pilot stage预试验阶段

 

I.3.3 Pivotal stage关键性阶段

 

I.3.4 Post-market stage上市后阶段

 

I.4 Type of clinical investigation design临床研究设计类型

 

I.4.1 General概述148

 

I.4.2 Exploratory clinical investigation探索性临床研究

 

I.4.3 Confirmatory clinical investigation验证性临床研究

 

I.4.4 Observational clinical investigation观察性研究

 

I.5 Descriptors of clinical investigations临床研究名词解释

 

I.5.1 General概述

 

I.5.2 First in human clinical investigation人类首次临床研究

 

I.5.3 Early feasibility clinical investigation早期可行性临床研究

 

I.5.4 Traditional feasibility clinical investigation传统的可行性临床研究

 

I.5.5 Pivotal clinical investigation关键性临床研究

 

I.5.6 Registry注册研究

 

I.6 Burden to subjects受试者负担

 

I.6.1 General概述

 

I.6.2 Interventional clinical investigation干预性临床研究

 

I.6.3 Non-interventional clinical investigation非干预性临床研究

 

I.7 Applicability of this document’s principles本文件原则的适用性

 

Annex J Clinical investigation audits 附件J 临床研究稽查

 

J.1 General概述

 

J.2 Sponsor申办者

 

J.3 Investigation site研究中心

 

Bibliography.

 

7.Clinical investigation conduct临床研究实施

 

7.1.General概述

 

The clinical investigation shall be conducted in accordance with the CIP.

 

临床研究应按照临床研究计划的要求进行。

 

The clinical investigation shall not commence until written approval/favourable opinion from the EC and, if required, the relevant regulatory authority of the countries where the clinical investigation is taking place has been received.

 

临床研究必须收到伦理委员会的书面批准/赞同意见才能开始，如果需要，在临床研究前由国家的监管机构进行审查。

 

The sponsor shall ensure ongoing risk management throughout the clinical investigation taking into consideration all aspects related to the investigational device, clinical procedures required by the CIP, and the investigation process (see 6.2 and 7.4.4).

 

申办者应确保在整个临床研究过程中持续进行风险管理，并考虑到与研究器械、临床研究计划要求的临床流程和研究过程相关的所有方面（见6.2和7.4.4）。

 

7.2.Investigation site initiation研究中心启动

 

An initiation visit for each participating investigation site or, alternatively, an investigator meeting shall be conducted and documented by the sponsor or monitor at the beginning of the clinical investigation (see 9.2.4.4). A log shall be initiated identifying names, initials, signatures, functions, and designated authorisations for the principal investigator and members of the investigation site team.

 

在临床研究开始时，申办者或监查员执行并记录每家研究中心的首次访视或研究者会议（见9.2.4.4）。应创建一个日志用于识别主要研究员和研究中心小组成员的姓名、首字母、签名、职责和授权。

 

NOTE：Depending on the type and complexity of the clinical investigation, and its associated risks, site initiation can be performed by a telephone call or other communication, as specified in the risk-based monitoring plan.

 

注：根据临床研究的类型、复杂性及其相关风险，根据基于风险的监查计划的规定，可以通过电话或其他通信方式进行现场启动。

 

7.3.Investigation site monitoring研究中心监查

 

The conduct of the clinical investigation shall be monitored according to the monitoring plan (see 6.7 and 9.2.4).

 

临床研究的实施应按照监查计划（见6.7和9.2.4）。

 

The results of all monitoring activities (on-site [see 9.2.4.7] and centralized) shall be documented.

 

应记录所有监查活动（现场监查见9.2.4.7）的结果。

 

7.4.Adverse events and device deficiencies不良事件和器械缺陷

 

7.4.1. Signals requiring immediate action需要立即采取行动的信号

 

Signals from adverse events or device deficiencies that might indicate a serious health threat can be detected by either the sponsor or principal investigator but are evaluated by the sponsor.

 

申办者或主要研究者可能会发现需要由申办者进行评估的严重威胁健康的不良事件或器械缺陷信号。

 

Any occurrence of a serious health threat can require a specific reporting process according to regulatory requirements as specified in 9.2.5.

 

根据9.2.5中规定的监管要求，任何严重威胁健康的事件都需要特定的报告流程。

 

7.4.2. Adverse events不良事件

 

All adverse events and any new information concerning these events shall be documented in a timely manner throughout the clinical investigation and shall be reported as specified in 9.2.5 and 10.8 (for adverse event categorization, see Annex F).

 

在整个临床研究过程中，所有不良事件和有关这些事件的任何新信息都应及时记录下来，并应按照9.2.5和10.8的规定进行报告(不良事件分类见附件F)。

 

NOTE 1 This includes adverse events identified in the CIP as critical to the evaluation of the results of the clinical investigation.

 

注1：这包括临床研究计划中确定的对临床研究结果评估至关重要的不良事件。

 

NOTE 2 Adverse events associated with users or other persons can be documented separate from adverse events associated with the subject, taking into account the data privacy regulations (see 7.7).

 

注2：考虑到数据隐私法规，与用户或其他人的不良事件可以同与受试者相关的不良事件分开记录(参见 7.7).

 

NOTE 3 Certain national regulations can apply to reporting of adverse events during post-market clinical investigations.

 

注3：某些国家特定法规可适用于上市后临床研究中的不良事件报告。

 

All adverse events shall be reported in an interim or final report of the clinical investigation.

 

所有不良事件均应在临床研究的中期或最终报告中进行报告。

 

7.4.3. Device deficiencies器械缺陷

 

All device deficiencies of an investigational device shall be documented throughout the clinical investigation and managed by the sponsor in accordance with written procedures for the control of a non-conforming product. The sponsor shall take, where applicable, appropriate corrective and preventive actions to protect the safety of subjects, users, and other persons. Device deficiencies of the comparator, if applicable, shall be documented.

 

研究器械的所有器械缺陷都应记录，并由申办者按照控制不合格产品的标准操作流程进行管理。申办者应在合适的情况下采取适当的纠正和预防措施，以保护受试者、使用者和其他人的安全。如果适用，对照器械的器械缺陷也应记录。

 

The sponsor shall arrange for the safe return of the investigational device that is related to the device deficiency (see 7.9).

 

申办者应安排与器械缺陷相关的研究器械的召回（见7.9）。

 

Device deficiencies that did not lead to an adverse event but could have led to a serious adverse device effect

 

未导致不良事件但可能导致器械相关严重不良反应的器械缺陷

 

a) if either suitable action had not been taken,

 

如果没有采取适当的行动，

 

b) if intervention had not been made, or

 

如果没有进行干预，或者

 

c) if circumstances had been less fortunate,

 

如果情况不那么幸运，

 

shall be reported as specified in 9.2.5 and 10.8. Where applicable, the analysis of used or explanted investigational devices shall be included as supportive information.

 

应按照9.2.5和10.8中的规定进行报告。在适当的情况下，对已使用或植入的研究器械的分析应作为支持性信息纳入其中。

 

7.4.4. Risk assessment process for potentially unacceptable risks对潜在不可接受风险的风险评估过程

 

Risks arising during the course of a clinical investigation shall be managed as follows (see Figure H.1).

 

临床研究过程中产生的风险应按以下方式进行管理（见图H.1）。

 

a) Any person identifying an event or information that could have an impact on subjects’, users’ or other persons’ safety, has an obligation to inform the principal investigator and the sponsor of their concerns.

 

当任何个人发现可能影响受试者、用户或其他人安全的事件或信息时，都有义务告知所涉及的主要研究者和申办者。

 

b) Risks are monitored against established risk acceptability thresholds.

 

根据已建立的风险可接受性阈值来监测风险。

 

c) When circumstances of concern have been recognized, a preliminary risk analysis shall be performed by the sponsor in consultation with the principal investigator and, if appropriate, other advisors. The preliminary risk analysis can lead to the following outcomes.

 

当发现有问题的情况时，申办者应与主要研究者并在适当情况下与其他顾问协商，进行初步风险分析。初步风险分析可能导致以下结果。

 

1) The new information is adequately reflected in the existing risk assessment and the individual and overall residual risks to subjects, users, or other persons remain acceptable. The sponsor shall ensure that a rationale for this is recorded in the clinical investigation documentation.

 

现有风险评估充分反映了新情况，受试者、使用者或其他人的个人和群体剩余风险仍然可以接受。申办者应确保记录在临床研究文件中的合理性。

 

2) Where possible, unacceptable risk or serious health threat has been identified, the sponsor shall suspend the clinical investigation immediately and the preliminary risk analysis shall be documented and notified to the interested parties as required in 8.2.1, while further investigation is conducted.

 

在可能的情况下，发现不可接受的风险或严重威胁健康时，申办者应立即暂停临床研究，初步风险分析应记录在案，并按照8.2.1的要求通知相关方，同时进行进一步调查。

 

d) Where a preliminary risk analysis has resulted in the recognition of the possibility of an unacceptable risk, the sponsor shall make appropriate arrangements for a comprehensive risk assessment in compliance with ISO 14971. Where appropriate, a DMC or expert advisors should provide input into or conduct the risk assessment (see 8.2.1).

 

如果初步风险分析确认可能存在不可接受的风险，申办者应根据ISO 14971进行全面风险评估。在适当的情况下，数据监查委员会或专家顾问应对风险评估进行分析或评估(见 8.2.1).

 

e) The comprehensive risk assessment can lead to the following outcomes.

 

全面的风险评估可导致以下结果。

 

1) The new information is adequately reflected in the existing risk assessment and individual and overall residual risks to subjects, users or other persons remain acceptable. The sponsor shall ensure that a rationale for this is recorded in the clinical investigation documentation and necessary activities are performed before resuming the clinical investigation (see 8.2.2).

 

新的信息充分反映在现有的风险评估中，对受试者、使用者或其他人的个人和群体剩余风险仍可接受。申办者应确保记录在临床研究文件中的合理性，并在恢复临床研究前进行必要的动作(见 8.2.2).

 

2) Corrective actions can be applied, including the following options:

 

可以采取纠正措施，包括以下措施：

 

f) if the corrective actions do not affect the validity of the clinical investigation, the sponsor shall revise the benefit-risk analysis to justify continuation of the clinical investigation; perform necessary activities before resuming the clinical investigation (see 8.2.2); see Figure H.1 for impact on clinical investigation documents;

 

如果纠正措施不影响临床研究的有效性，申办者重新审视受益-风险分析，以证明继续进行临床研究的合理性；在恢复临床研究前进行必要的活动（见 8.2.2)；对临床研究文件的影响见图H.1。

 

g) if the corrective actions affect the validity of the clinical investigation, the clinical investigation shall be terminated.

 

如果纠正措施影响临床研究的有效性，临床研究应终止。

 

1) If corrective actions cannot be applied, the clinical investigation shall be terminated.

 

如果不能采取纠正措施，临床研究应终止。

 

7.5.Clinical investigation documents and documentation临床研究文件和文档

 

7.5.1. Amendments修订

 

The IB, CIP, CRFs, informed consent form and other subject information, or other clinical investigation documents such as instructions for use shall be amended as needed throughout the clinical investigation in accordance with written procedures for the control of documents and document changes.

 

研究者手册、临床研究计划、病例报告表、知情同意书和其他受试者信息，或其他临床研究文件，如使用说明书，应根据文件和文件变更版本控制要求，在整个临床研究过程中根据需要进行修订。

 

Documentation of changes shall include a description of the changes, justification of the changes and their potential impact on the performance, effectiveness, safety or other endpoints, and identification of the affected documents.

 

变更文件应包括变更的描述、变更的理由及其对性能、有效性、安全性或其他终点的潜在影响，以及受影响文件的识别。

 

Proposed amendments to the CIP shall be reviewed and approved by the same parties as specified in 6.4, unless specifically designated otherwise. The amendments to the CIP and the subject's informed consent form shall be notified to, or approved by, the EC and regulatory authorities, if required (see 5.6.4). The version number and date of amendments shall be documented.

 

除非另有特别规定，提出对临床研究计划修订应根据6.4中规定的交由相关各方进行审查和批准。如有需要，临床研究计划和受试者知情同意书的修订应通知伦理委员会或监管机构，或由其批准（见5.6.4）。应记录版本号和修改日期。

 

If the amendment impacts the integrity of the clinical investigation, the data collected before and after the amendment shall be analysed statistically to assess the effect of the amendment on performance, effectiveness or safety analysis. This analysis shall be included in the clinical investigation report.

 

如果修订内容影响了临床研究的完整性，则应对修订前后收集的数据进行统计分析，以评估修订对性能、有效性或安全性分析的影响。该分析应纳入临床研究报告。

 

7.5.2. Subject identification log受试者识别代码

 

Each investigation site shall maintain a log of all the subjects enrolled in the clinical investigation, assigning an identification code linked to their names, alternative subject identification or contact information.

 

每个研究中心应保存参与临床研究的所有受试者的记录，并指定与其姓名、替代受试者身份或联系信息相关的识别代码。

 

NOTE Depending on the clinical investigation design, a log can be maintained at the investigation site that identifies everyone who has been pre-screened for potential enrolment in the clinical investigation.

 

注：根据临床研究的设计，可以在研究中心保存一个鉴认代码表，以确定所有已被预先筛查并可能参加临床研究的人。

 

7.5.3. Source documents源文件

 

Source documents shall be created and maintained by the investigation site team throughout the clinical investigation. The type and location of these source documents shall be documented.

 

源文件应由整个临床研究过程中的研究中心团队创建和维护。应记录这些源文件的类型和位置。

 

7.6.Additional members of the investigation site team研究中心小组的额外成员

 

New members of the investigation site team may be added from time to time at new or existing sites. New personnel should only start their assignment after receiving adequate training in the clinical investigation requirements and this training shall be documented. The names, initials, signatures, functions, and designated authorisations of new personnel shall be documented.

 

研究中心小组的新成员可能会不时在新中心或现有中心增加。新成员应在充分接受临床研究所要求的培训后才开始任务，该培训应以予记录。应记录新成员的姓名、首字母缩写、签名、职能和职责授权。

 

NOTE  EC approval of new members of the investigation site team can be required before commencement of their responsibilities, in addition to internal site documentation of these responsibilities and new member training.

 

注：除了这些职责的内部现场文件和新成员培训外，研究中心团队的新成员在开始履行职责之前可能需要获得伦理委员会的批准。

 

7.7.Subject privacy and confidentiality of data受试者隐私和数据保密

 

Confidentiality of data shall be observed by all parties involved at all times throughout the clinical investigation. All data shall be secured against unauthorized access.

 

在整个临床研究过程中，各方应遵守数据的保密性。所有数据应防止未经授权的访问。

 

The privacy of each subject and confidentiality of his/her information shall be preserved in reports and when publishing any data.

 

在报告和发布任何数据时，应确保每个受试者的隐私和其信息的保密性。

 

The principal investigator or investigation site shall provide direct access to source data during and after the clinical investigation for monitoring, audits, EC review and regulatory authority inspections. As required, the principal investigator or investigation site shall obtain permission for direct access to source documents from the subject, hospital administration and regulatory authorities before starting the clinical investigation.

 

主要研究者或研究中心应在临床研究期间和之后确保可以直接访问源数据，以便用于监查、稽查、伦理审查和监管机构检查。根据需要，主要研究者或研究中心应在开始临床前获得从受试者、医院管理部门和监管机构那里获得直接访问源文件的许可。

 

7.8.Document and data control文件和数据控制

 

7.8.1. Traceability of documents and data文件和数据的可追溯性

 

All documents and data shall be produced and maintained in a way that ensures reliability, integrity, control and traceability. All documents, and subsequent versions, related to a clinical investigation shall be identifiable, traceable and appropriately stored to provide a complete history of the clinical investigation. Where relevant, the accuracy of translations shall be guaranteed and documented.

 

所有文件和数据的生产和维护应确保可靠性、完整性、可控性和可追溯性。与临床研究相关的所有文件和后续版本应是可识别的、可追溯的，并适当存储以提供完整的临床研究历程。在某些情况下，应保证并记录翻译的准确性。

 

The investigator shall ensure the accuracy, attribution, completeness, legibility and timeliness of the data reported to the sponsor on the CRFs and in all required reports. All copies of the retained original source documents shall be certified, as indicated by a dated signature by a member of the investigation site team unless generated through a validated process. Special requirements should be applied to the capture, review and retention of electronic source data, to ensure reliability, quality, integrity and traceability (see Reference [12]).

 

研究者应确保在病例报告表和所有需要报告给申办者的数据的准确性、属性、完整性、可读性和及时性。所有保留的原始源文件的副本都应经过认证，并由研究中心小组成员的签名注明日期，除非是通过经验证的流程生成。对电子源数据的获取、审查和存档应有特殊要求，以确保可靠性、质量、完整性和可追溯性(见参考文献 [12])。

 

If assignment to a treatment group is blinded/masked in any way, it shall be safeguarded throughout the clinical investigation, including data entry and processing. Written procedures for decoding blinded/ masked clinical investigations shall be followed.

 

如果治疗组的分配采用某种盲法或掩盖，则应在整个临床研究过程中予以维护，包括数据输入和处理。应遵循揭盲/设盲临床研究的操作流程。

 

7.8.2. Recording of data数据记录

 

The data reported on the CRFs shall be derived from source documents and be consistent with these source documents, and any discrepancies shall be explained in writing. The CIP shall specify which data can be recorded directly in the CRFs.

 

病例报告表上报告的数据应来自于源文件，并与这些源文件相一致，任何差异应以书面形式解释。临床研究计划应规定哪些数据可以直接记录在病例报告表中。

 

NOTE 1 The acceptance of direct entry of source data in the CRF can be subject to a hospital’s specific documentation requirements.

 

注1：在病例报告表中直接输入源数据可受制于医院的具体文件要求。

 

NOTE 2 Data that can be directly recorded in the CRFs can also be documented in the monitoring plan.

 

注2：可直接记录在病例报告表中的数据也可以注明在监查计划中。

 

The CRFs shall be signed and dated by the principal investigator or his/her authorized designee(s). Any change or correction to data reported on a CRF shall be dated, initialled and explained if necessary, and shall not obscure the original entry (i.e. an audit trail shall be maintained); this applies to both written and electronic changes or corrections.

 

病例报告表应由主要研究者或经授权的指定人员签署并注明日期。对病例报告表上报告中的任何数据进行变更或更正时应注明日期、姓名缩写，必要时应予以解释，且不得掩盖原始记录（即应保持稽查轨迹）；这适用于纸质和电子修改或更正。

 

The sponsor shall:

申办者应：

 

a) provide guidance to the principal investigators or his/her authorized designee on making such corrections; the sponsor shall have written procedures to ensure that changes or corrections in CRFs are documented, are necessary, are legible and traceable, and are endorsed by the principal investigator or his/her authorized designee; records of the changes and corrections shall be maintained,

 

指导主要研究者或其授权指定人员作出正确的变更；申办者应制定标准操作流程以确保病例报告表中的变更或更正是有文件记录的，是必要的，是清晰和可追溯的，并由主要研究者或其授权指定人员认可；应保存变更和更正的记录，

 

b) ensure that it is possible to compare the original data and observations with the processed data, if data are transformed during processing;

 

如果数据在采集过程中进行转换，确保原始数据和处理后的观测数据可以进行比较。

 

c) use an unambiguous subject identification code that allows identification of all the data reported for each subject. The link between the code and each subject shall be retained by the principal investigator in a secure location.

 

使用一个明确的受试者识别代码以识别每个受试者所报告的所有数据。识别代码和每个受试者之间的关联应由主要研究者保留在一个安全的地方。

 

7.8.3. Electronic clinical data systems临床电子数据系统

 

Validation of electronic clinical data systems is necessary in order to evaluate the authenticity, accuracy, reliability, and consistent intended performance of the data system from design until decommissioning of the system or transition to a new system.

 

临床电子数据系统的验证是必要的，以评估数据系统的真实性、准确性、可靠性，以及从设计到系统退役或转移到另一个新系统的预期一致性。

 

These requirements are applicable to any electronic records as defined in 3.21, including electronic CRFs, electronic systems used for entering and processing data from paper CRFs received from sites and other electronic systems required in the clinical investigation.

 

这些要求适用于3.21中定义的任何电子记录，包括电子病例报告表、用于输入和处理从中心接收的纸质病例报告表数据的电子系统以及临床所需的其他电子系统。

 

When electronic clinical databases or electronic clinical data systems are used, written procedures shall be implemented to

 

当使用电子临床数据库或临床电子数据系统时，应按约定的流程执行

 

a) describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning,

 

描述系统验证和功能测试、数据收集和处理、系统维护、系统安全措施、变更控制、数据备份、恢复、应急计划，和退役，

 

b) establish and document requirements for the electronic clinical data system to receive and process data,

 

建立和记录临床电子数据系统接收和处理数据的要求，

 

c) verify and validate that the requirements for the electronic clinical data system can be consistently met,

 

确认并验证临床电子数据系统的要求可以符合一致性要求，

 

d) ensure attributability, completeness, reliability, consistency, and logic of the data entered,

 

保数据的属性、完整性、可靠性、一致性和数据录入的逻辑性，

 

e) ensure accuracy of reports,

 

确认报告的准确性，

 

f) ensure that data changes are documented and that there is no deletion of entered data, i.e. maintain an audit trail, data trail and edit trail,

 

确保数据变更被记录下来，并且没有删除输入的数据，如维护稽查轨迹、数据轨迹和编辑轨迹，

 

NOTE：National regulations on data protection can require deletion.

 

注：国家数据保护法规可能需要删除。

 

g) maintain a security system that prevents unauthorized access to the data, both internally and externally,

 

维护一个安全系统，防止在内部和外部未经授权地访问数据，

 

h) maintain a list of individuals who have access to the electronic data system as well as the dates of access, privileges granted to each user and removal of access,

 

维护一份可以访问电子数据系统的个人名单，以及访问日期、授予每个用户的权限和取消访问权限，

 

i) ensure the accuracy and completeness of the data reported to the sponsor in the CRFs by implementing a signature by the principal investigator or authorized designee,

 

通过主要研究者或授权指定人员的签名，确保报告给申办者的数据的准确性和完整性，

 

j) maintain adequate backup, retention and retrievability of the data,

 

维护数据足够的备份、存档和可检索性，

 

k) train users on the use of the system, and

 

培训用户了解如何使用该系统，以及

 

l) safeguard the blinding, if any (e.g. maintain blinding during data entry, and processing).

 

如果设盲应以予保持（例如在数据输入和处理过程中保持盲态）。

 

7.9.Investigational device accountability研究器械管理

 

Access to investigational devices shall be controlled and the investigational devices shall be used only in the clinical investigation and according to the CIP.

 

研究器械的使用应受到控制，研究器械应仅在临床研究并根据临床研究计划使用。

 

The sponsor shall keep records to document the physical location of all investigational devices from shipment of investigational devices to the investigation sites until return or disposal. The sponsor shall have instructions in place and make packaging materials available, if applicable, for the safe return or disposal of investigational devices, including potentially hazardous devices. The principal investigator or an authorized designee shall keep records documenting the following:

 

申办者应保存记录，以记录所有研究器械的从研究器械运输到研究中心到回收或处置的存放位置。申办者应有适当的说明，并提供包装材料，用于安全回收或处置研究器械，包括潜在危险的器械。主要研究者或授权人员应当记录以下内容：

 

a) name(s) of person(s) who received, used, returned, or disposed of the device;

 

接收、使用、归还或处置这些器械的人员姓名；

 

b) the date of receipt, identification, and quantity of each investigational device (batch number/serial number or unique code);

 

每个试验器械的接收日期、编码和数量（批号/序列号或唯一编码）；

 

c) the expiry date, if applicable;

 

失效日期，如有；

 

d) the date or dates of use;

 

使用日期；

 

e) subject identification;

 

受试者编码；

 

f) date on which the investigational device was returned/explanted from subject, if applicable;

 

受试者归还/移交研究器械的日期，如有；

 

g) the date of return of unused, expired, or malfunctioning investigational devices, if applicable;

 

归还未使用、过期或出现故障的研究器械的日期，如有；

 

h) the date and documentation of disposal of the investigational devices as per instructions of the sponsor, if applicable.

 

根据申办者的说明处置研究器械的日期和文件，如有；

 

Written procedures shall be established for the entire process of device accountability.

 

整个器械管理过程应建立标准操作流程。

 

7.10.Accounting for subjects受试者审查

 

All subjects enrolled in the clinical investigation (including those withdrawn from the clinical investigation or lost to follow-up) shall be accounted for and documented.

 

所有参与临床研究的受试者（包括退出临床研究或失访的受试者）应进行审查和记录。

 

If a subject discontinues participation in the clinical investigation, the reason(s) shall be recorded. The investigator can use existing data and ask for the subject's permission to collect follow-up data about his/her status/condition including information about device clinical performance, effectiveness or safety. If permission is obtained, the relevant data shall be included in the clinical investigation report.

 

如果受试者退出临床研究，应记录其原因。研究者可以使用现有的数据，并请求受试者许可收集其有关他/她的症状/健康的随访数据，包括相关器械的临床性能、有效性或安全性的信息。如获得许可，应将相关资料纳入临床研究报告。

 

NOTE：The collection of follow-up data from discontinued subjects can be subject to national regulations.

 

注：从退出的受试者中收集的随访数据受制于国家法规。

 

7.11.Auditing稽查

 

Audits of the clinical investigation may be conducted to evaluate compliance with the CIP, written procedures, this document and the applicable regulatory requirements (see Annex J). These audits may cover all involved parties, systems, processes, and facilities, and are independent of, and separate from quality control functions or routine monitoring.

 

可以对临床研究进行稽查，以评估对临床研究计划、操作流程、本文件和适用的法规要求的符合性(见附件J)。这些稽查可能涵盖所有相关方、系统、流程和设施，并独立于质量控制或常规监查。

 

An audit can be used

 

稽查可以用于以下情况：

 

a) as a routine part of the sponsor's quality assurance,

 

作为申办者质量保证的一个常规部分，

 

b) to assess the effectiveness of the monitoring activity,

 

评估监查活动的有效性，

 

c) whenever there are serious or repeated CIP deviations or suspicion of fraud,

 

每当有严重或反复的临床研究计划偏离或怀疑欺诈时，

 

d) to bring an investigation site into “inspection readiness” (i.e. to prepare the investigation site for a potential regulatory inspection),

 

使研究中心进入“检查准备状态”(即，研究中心为潜在的监管机构检查做准备查），

 

e) when requested or suggested by a regulatory authority.

 

当被监管机构要求或建议时。

 

The auditors shall be qualified by training and experience to conduct audits and shall be independent of the clinical investigation.

 

稽查员应进行相应的培训并具有稽查经验，且应独立于临床研究。

 

The auditing of clinical investigation systems and processes shall be conducted in accordance with written procedures or specific plan on what to audit, how to audit, the frequency of audits, and the form and content of audit reports and audit certificates.

 

临床研究体系和流程的稽查应按照操作流程或特定计划确认稽查内容、稽查方式、稽查频率、稽查报告的形式和内容，以及稽查证明书。

 

The audit plan or procedures for a clinical investigation audit shall be guided by the importance of the clinical investigation, the number of subjects in the clinical investigation, the type and complexity of the clinical investigation, the level of risk to the subjects and any identified problem(s).

 

临床研究稽查的稽查计划或流程应以临床研究的重要性、临床研究对象的数量、临床研究的类型和复杂性、对受试者的风险水平以及任何已确定的风险为指导。

 

The audit results shall be documented and communicated to relevant parties. If applicable, an audit certificate shall be kept in the sponsor files.

 

稽查结果应被记录下来，并传达给相关各方。如适用，应在申办者文件中保存稽查证明书。

 

8.Suspension, termination, and close-out of the clinical investigation暂停、终止和结束临床研究

 

8.1.Completion of the clinical investigation完成临床试验

 

The completion of a clinical investigation shall be deemed to coincide with the last visit of the last subject and when follow-up is complete for the clinical investigation, whether the clinical investigation concluded according to the pre-specified clinical investigation plan or was terminated prematurely, unless another point in time for such end is set out in the clinical investigation plan.

 

临床研究的完成应视为末例受试者的末次随访与临床研究随访完成同时发生，无论临床研究是否按照预先制定的临床研究计划结束或提前终止，除非临床研究计划为试验完成规定了另一个时间点。

 

NOTE Completion of a clinical investigation can also be referred to as the end of a clinical investigation.

 

注：临床研究的完成也可以称为临床研究的结束。

 

8.2.Suspension or premature termination of the clinical investigation暂停或提前终止临床研究

 

8.2.1. Procedure for suspension or premature termination暂停或提前终止的程序

 

The sponsor may suspend or prematurely terminate either a clinical investigation at an individual investigation site or the entire clinical investigation for significant and documented reasons, such as when recommended by the DMC.

 

申办者可因重大的和有记录的原因，如在数据监查委员会推荐的情况下，暂停或提前终止在个别研究中心或整个临床研究。

 

A principal investigator, EC, or regulatory authority may suspend or prematurely terminate participation in a clinical investigation at the investigation sites for which they are responsible.

 

主要研究者、伦理委员会或监管机构可暂停或提前终止他们所负责的研究中心的临床研究。

 

If suspicion of an unacceptable risk, including serious health threat to subjects, arises during the clinical investigation, or when so instructed by the EC or regulatory authorities, the sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor shall terminate the clinical investigation if an unacceptable risk which cannot be controlled is confirmed (see 7.4.4 and Figure H.1).

 

如果在临床研究过程中怀疑存在不可接受的风险，包括在临床研究中出现对受试者有严重健康威胁，或在伦理委员会或监管机构的指示下，申办者应暂停临床研究以评估风险。如果确认存在无法控制的不可接受的风险，申办者应终止临床研究（见图7.4.4和图H.1）。

 

The sponsor shall consider terminating or suspending the participation of a particular investigation site or investigator in the clinical investigation if monitoring or auditing identifies serious or repeated deviations on the part of an investigator.

 

如果监查或稽查中发现部分研究者出现严重或反复的偏离时，申办者应考虑终止或暂停某家研究中心或研究者参与临床研究。

 

If suspension or premature termination occurs, the terminating party shall justify its decision in writing and promptly inform the other parties with whom they are in direct communication.

 

如发生暂停或提前终止，终止方应以书面形式证明其决定的合理性，并立即通知与其直接沟通的其他相关方。

 

NOTE 1 The usual lines of communication are sponsor <-> principal investigator or sponsor <-> EC and sponsor <-> regulatory authority.

 

注1：通常的沟通线路是申办者<->主要研究者或申办者<->伦理委员会和申办者<->监管机构

 

The principal investigator and sponsor shall keep each other informed of any communication received from either the EC or the regulatory authority.

 

主要研究者和申办者应随时告知从伦理委员会或监管机构收到的任何信息。

 

If, for any reason, the sponsor suspends or prematurely terminates the investigation at an individual investigation site, the sponsor shall inform the responsible regulatory authority as appropriate and ensure that the EC is notified, either by the principal investigator or by the sponsor. If the suspension or premature termination was in the interest of safety (see 7.4.4 and Figure H.1) the sponsor shall inform all other principal investigators.

 

如果申办者出于任何原因暂停或提前终止在个别研究中心的研究，申办者应适当地通知负责的监管机构，并确保由主要研究者或申办者通知伦理委员会。如果暂停或提前终止为了安全（见7.4.4和图H.1），申办者应通知所有其他主要研究者。

 

If suspension or premature termination occurs,

 

如果暂停或提前终止发生，

 

a) the sponsor shall remain responsible for providing resources to fulfil the obligations for following up the subjects enrolled in the clinical investigation, and

 

申办者应继续负责提供资源，以履行对参与临床研究的受试者的随访义务，以及

 

b) the principal investigator or authorized designee shall promptly inform the enrolled subjects at his/her investigation site, if appropriate.

 

主要研究者或授权指定人员应立即通知在其研究中心招募的受试者，如果合适。

 

NOTE 2 The method and the timing of this communication depends on the circumstances, the perceived risks, and national regulations.

 

注2：这种沟通的方法和时间取决于情况、预知的风险和国家法规。

 

All activities listed in 8.3 shall also be conducted.

 

8.3中列出的所有活动也应进行。

 

8.2.2. Procedure for resuming the clinical investigation after temporary suspension恢复暂停后的临床研究程序

 

When the sponsor concludes an analysis of the reason(s) for the suspension, implements the necessary corrective actions, and decides to lift the temporary suspension, the sponsor shall inform the principal investigators, the ECs, and, where appropriate, the regulatory authority of the rationale and provide them with the relevant data supporting this decision.

 

当申办者对暂停的原因进行分析，实施必要的纠正措施并决定解除暂停时，申办者应通知主要研究者、伦理委员会。在必要的情况下，向监管机构应提供理由并向其提供支持该决定的相关数据。

 

NOTE The usual lines of communication are sponsor <-> principal investigator or sponsor <-> EC and sponsor <-> regulatory authority.

 

注意：通常的沟通线路是申办者<->主要研究者或申办者<->伦理委员会和申办者<->监管机构

 

Concurrence shall be obtained from the ECs and, where appropriate, regulatory authorities before the clinical investigation resumes.

 

在临床研究恢复前，应获得伦理委员会，必要时还应获得监管机构的同意。

 

If subjects have been informed of the suspension, the principal investigator, or authorized designee shall inform them of the reasons for resumption.

 

如果受试者已被告知暂停，主要研究者或授权指定人员应告知他们重新开始的原因。

 

8.3.Routine close-out常规关中心

 

Routine close-out activities shall be conducted to ensure that the principal investigator's records are complete, all documents needed for the sponsor's files are retrieved, remaining clinical investigation materials are disposed of, previously identified issues have been resolved, and all parties are notified.

 

应进行常规的关中心动作，以确保主要研究者的记录完整、所有申办者所需的文件都归档、剩余的临床研究物资得到处理、先前确认的问题得到解决，并通知各相关方。

 

a) Completing the records includes ensuring that

 

完成记录以确保

 

1) all essential documents are complete and up to date,

 

所有必要的文件都是完整且为最新，

 

2) all CRFs are completed,

 

所有的病例报告表都完成，

 

3) all outstanding queries are resolved,

 

所有未解决的质疑都已解决，

 

4) the current status of all ongoing adverse events is documented,

 

所有持续的不良事件的当前状态都已经记录，

 

5) arrangements are made for archiving and record retention, and

 

已经为存档和记录保存做出安排，以及

 

6) documenting disposition of any:

 

记录任何物资处置情况：

 

i) investigational devices;

 

研究器械；

 

ii) remaining samples (e.g. blood or tissue);

 

剩余样本（例如，血液或组织）；

 

iii) other clinical investigation materials.

 

其他临床研究物资。

 

b) Notification includes:

 

通知包括：

 

1) notification to EC;

 

通知伦理委员会；

 

2) notification to regulatory authorities, if required;

 

通知监管机构，如必要；

 

NOTE：Certain national regulations can also require this to be done within specific timelines.

 

注：某些国家法规也可能要求在特定时间内完成。

 

3) notification of clinical investigation completion in publicly accessible database (see 5.4).

 

在公开访问的数据库中通报临床研究完成(见 5.4).

 

8.4.Clinical investigation report临床研究报告

 

After close-out of the clinical investigation, a report of the clinical investigation shall be completed, even if the clinical investigation was terminated prematurely. The clinical investigation report shall include the information specified in Annex D.

 

临床研究结束后，即使临床研究提前终止，也应完成临床研究报告。临床研究报告应包括附件D中规定的内容。

 

NOTE 1：National regulations can apply to the requirements of the clinical investigation report completion and reporting.

 

注1：国家法规可能会对临床研究报告完成和报告内容提出要求。

 

a) The clinical investigation report shall be in written form.

 

临床研究报告应以书面形式完成；

 

b) The clinical investigation report shall include identification of the device(s), a description of the methodology and design of the clinical investigation, any deviations from the CIP, data analysis together with any statistics, and a critical appraisal of the results compared to the objectives of the clinical investigation.

 

临床研究报告应包括器械的识别、临床研究的方法和设计的描述、对方案的任何偏离、采用各类统计方法的数据分析结果，并对结果与临床研究目标进行了批判性评估。

 

c) The results reported in the clinical investigation report shall be derived from data reported on the CRFs and other applicable data capture methods in a repeatable and traceable manner. Records shall be kept demonstrating this.

 

临床研究报告中的结果应以可重复和可追溯的方式来自于病例报告表的数据和其他必要的数据采集方法。应保存证明这一点的记录。

 

d) The clinical investigation report shall take into account the data from each investigation site and for all subjects. No subject shall be identifiable either from the clinical investigation report or the published results.

 

临床研究报告应考虑每个研究中心和所有受试者的数据。无论是从临床研究报告还是公布的结果中，都不能识别任何受试者。

 

e) The clinical investigation report shall be made available to the coordinating investigator where applicable, and all principal investigators for review and comment. The sponsor shall maintain records confirming that the clinical investigation report has been provided for review. If a reviewer does not agree with all or part of the clinical investigation report, his/her comments shall be recorded and communicated to the other principal investigators.

 

临床研究报告应在适用时提供给协调研究者和所有主要研究者进行审查和评论。申办者应进行记录，确认已提供临床研究报告以供审查。如果审稿人不同意全部或部分临床研究报告，应记录其意见并传达给其他主要研究者。

 

f) The sponsor and coordinating investigator shall be asked to provide their signatures, indicating their agreement with the content of the clinical investigation report. If no coordinating investigator is appointed, the signature of the principal investigator(s) shall be obtained.

 

应要求申办者和协调研究者提供其签名，表明其对临床研究报告内容的同意。如果没有指定协调研究者，应获得主要研究者的签字。

 

g) The clinical investigation report shall be provided to the EC(s) and regulatory authorities.

 

临床研究报告应提供给伦理委员会和监管机构。

 

h) The results of the clinical investigation shall be entered in a publicly accessible database where the clinical investigation was registered (see 5.4) and published whether positive, inconclusive or negative, to help guide future research, device development and medical treatment.

 

临床研究的结果应录入临床研究所登记的公开数据库(见 5.4)并发表了一些文章，无论是正向的、不确定的、还是反向的，以帮助指导未来的研究、器械开发和医学治疗。

 

NOTE 2：Further guidance on the content of the clinical investigation report is given in Annex D.

 

注2：关于临床研究报告内容的进一步指导见附录D。

 

8.5.Risk assessment and conclusions风险评估和结论

 

A formal review of risk information should be carried out upon completion of the clinical investigation (see D.8) and fed into the risk analysis and clinical evaluation with an update of the benefit-risk conclusions in both documents.

 

在临床研究完成后(见D.8)应对风险信息进行正式审查，并纳入风险分析和临床评价并更新两份文件中的受益-风险结论。

 

8.6.Document retention文件保存

 

The sponsor and principal investigator shall maintain the clinical investigation documents. They shall take measures to prevent accidental or premature destruction of these documents. The principal investigator or sponsor may transfer custody of records to another person/party and document the transfer at the investigation site or at the sponsor's facility.

 

申办者和主要研究者应保存临床研究文件。他们应采取措施，防止这些文件的意外或过早销毁。主要研究者或申办者可将研究中心或申办者机构内的文件保管转移给另一人/机构。

 

NOTE A list of essential clinical investigation documents to be maintained in sponsor and investigation site files is given in Annex E.

 

注：申办者需保存的必要临床研究文件清单和研究中心文件见附件E.

 

Clinical investigation documents, including but not limited to CIP, IB, CRF and clinical investigation report(s) should be incorporated into the device technical documentation under the quality management system of the manufacturer. For sponsor-investigator initiated clinical investigations, this should be applied to the extent possible.

 

临床研究文件，包括但不限于研究方案、研究者手册、病例报告表和临床研究报告，应整合至制造商质量管理体系下的医疗器械技术文件。对于申办者-研究者发起的临床研究，应尽可能地参考上述原则。

 

9.Responsibilities of the sponsor申办者的职责

 

9.1.Clinical quality management临床质量管理

 

Quality management principles shall apply to the processes of the clinical investigation to ensure that the clinical investigation is designed, conducted, and monitored, and that data are generated, documented, recorded, evaluated, and reported in compliance with this document, the CIP, any subsequent amendment(s), and any other applicable standards and in accordance with regulatory requirements. The sponsor shall

 

质量管理原则应运用于临床研究过程，以确保临床研究的设计、实施、监查，以及数据的生成、文件化、记录、评价、报告依从于本文件、研究方案、任何后续修订和任何其他适用标准，同时符合法规要求。申办者应该

 

a) implement and maintain written clinical quality procedures,

 

实施和维护已经制定的临床质量流程，

 

b) maintain records to document the compliance of all parties involved in the clinical investigation,

 

维护记录，以记录参与临床研究的各方的合规性，

 

c) ensure that the auditing requirements of 7.11 are met, if applicable, and

 

确保符合7.11的稽查要求，如果适用，以及，

 

d) justify and document significant exceptions to the requirements of this document (see Annex I for examples of exemptions).

 

证明并记录本文件要求以外的重大情况（豁免示例见附件I）。

 

Clinical quality procedures can be integrated in the applicable sections of the sponsor's overall quality system.

 

临床质量流程可以整合到申办者的整个质量体系的适用部分。

 

NOTE：For further information, see ISO 13485 or equivalent regulatory requirements.

 

注：有关更多信息，请参见ISO 13485或同等的法规要求。

 

9.2.Clinical investigation planning and conduct临床研究的计划和实施

 

9.2.1. Selection and training of clinical personnel临床工作人员的选择和培训

 

Prior to commencement of the clinical investigation, the sponsor shall

 

在临床研究开始前，申办者应负责

 

a) define, establish, and allocate all the roles and responsibilities related to the clinical investigation in one or more written agreements, as defined in 6.9,

 

在一个或多个书面协议中定义、确认和分配与临床研究相关人员的所有角色和责任，如6.9定义，

 

b) select a local representative if the sponsor is not resident in the country (countries) in which the clinical investigation is to be carried out, who acts as the sponsor fulfilling responsibilities of the sponsor in that country (those countries),

 

如果申办者不是拟进行临床研究所在国的居民，则需要选择一名当地代理人以履行申办者在该国（这些国家）的全部责任。

 

NOTE：National or regional regulations can apply to the requirements of local representative selection.

 

注：国家或地区法规可能有涉及代理人选择的要求。

 

c) select appropriately qualified principal investigators, as outlined in 6.8 and 10.2,

 

选择适当的合格的主要研究者，如中6.8和10.2所述，

 

d) select a coordinating investigator, if appropriate, as in the case of a multicentre investigation,

 

如有必要，进行多中心研究时选择一个协调研究者，

 

e) receive disclosures of conflict of interest from principal investigators and investigators,

 

对主要研究者和研究者的利益冲突进行披露，

 

f) ensure the members of the investigation site team and their designated authorization(s) are identified in a log with details, as defined in 7.2,

 

确保研究中心团队成员及其指定授权人员在正式记录中得到确认，如中7.2所述，

 

g) designate or appoint one or more monitors, who are independent from the investigation site(s), or otherwise assume the responsibilities of the monitor(s),

 

指定或任命一名或多个独立于研究中心的监查员，或以其他方式承担监查员的职责，

 

h) ensure documentation and verification of training, experience, and scientific or clinical knowledge for all the relevant parties involved in order to adequately conduct the clinical investigation, including training, on

 

确保所有相关方的培训、经验、科学或临床知识得以记录和验证，以便足以实施临床研究，包括在以下方面的培训：

 

1) the use of the investigational device(s) and where relevant the comparator,

 

研究器械以及相关对照产品的使用，

 

2) device accountability procedures (see 7.9),

 

研究器械管理，

 

3) IB,

 

研究者手册，

 

4) CIP,

 

临床研究计划，

 

5) CRFs,

 

病例报告表，

 

6) the written informed consent form and process as well as other written information provided to subjects, and

 

提供给受试者的书面知情同意书、流程以及其他书面信息，以及

 

7) sponsor's written procedures, this document and applicable regulatory requirements;

 

申办者的标准操作流程、本文件和适用的监管法规所需的东西；

 

i) ensure that, in multicentre investigations, all investigators and all other parties involved are given instructions on uniformly assessing and documenting clinical and laboratory findings,

 

确保在多中心研究中，所有研究者和所有其他相关方都得到了关于统一对临床和实验室发现的评价和记录的指导，

 

j) ensure that any clinical investigation-related activities involving potential contact with subjects and sponsor representative(s) at the investigation site(s) are described in the CIP and the informed consent form, and that these activities occur in such a way that they do not bias the data integrity,

 

确保在研究方案和知情同意书中描述了任何涉及受试者和申办者代表潜在接触的临床研究相关活动，并且这些活动的发生方式不会使数据完整性产生偏离，

 

NOTE：Individuals such as monitors, field engineers, or product specialists, who provide technical expertise in the implementation of the clinical investigation, are examples of sponsor representatives.

 

注：在实施临床研究时提供技术专长的监查员、现场工程师或产品专家等都是申办者的代表。

 

k) consider the need for a DMC and, if appropriate, establish the committee.

 

如必要，考虑组建数据监查委员会。

 

9.2.2. Preparation of documents and materials文件和物资准备

 

Prior to commencement of the clinical investigation, the sponsor shall

 

在临床研究开始之前，申办者应该

 

a) prepare the documents, as described in Clauses 5, 6, and 7, and ensure they are approved by the relevant persons by dated signature; if required, copies shall be provided to all parties involved, and dated signatures obtained as appropriate,

 

按照第5条、第6条和第7条的规定准备文件，并确保相关人员签字批准；如果需要，应向所有相关方提供副本，必要时获得注明日期的签名，

 

b) ensure the accuracy of the translation, where relevant,

 

确保翻译的准确性，当相关时，

 

c) ensure that a supply of investigational devices, as characterized in 7.9, is available in a timely manner for the clinical investigation; investigational devices shall not be made available to the principal investigator until all requirements to start the clinical investigation are met,

 

确保及时为临床研究提供7.9所述的研究器械；在达到开展临床研究的所有要求之前，不得向主要研究者提供研究器械，

 

d) establish a procedure assuring device accountability, which enables the immediate identification and where necessary, the recall of devices used in the clinical investigation,

 

建立一个程序确保器械管理，以使得能够立即识别，并在必要时召回临床研究使用的器械，

 

e) provide insurance covering the cost of treatment of subjects in the event of clinical investigation- related injuries, if applicable,

 

在发生临床研究相关伤害的情况下，提供涵盖受试者治疗费用的保险，如必要，

 

NOTE：Certain national or local regulations can apply.

 

注：参考特定国家或地区的法规。

 

f) document any financial arrangements between the principal investigator or the investigation site and the sponsor,

 

记录主要研究者或研究中心与申办者之间的任何财务安排，

 

g) submit any required application(s) to begin the clinical investigation in a given country to the appropriate regulatory authority (authorities) for review, acceptance or permission,

 

向相关监管机构提交在特定国家开始临床研究所需的任何申请，以供审查、批准或许可，

 

h) ensure that EC's approval/favourable opinion is obtained and documented, and that appropriate provisions are made to meet any conditions imposed by the EC,

 

确保获得伦理委员会的批准/赞成意见并形成文件，并作出适当的条款以满足伦理委员会所规定的任何条件，

 

i) ensure that any modification(s) required by the EC or regulatory authority are made and documented by the principal investigator and have gained the approval/favourable opinion of the EC or regulatory authority,

 

确保伦理委员会或监管机构要求的任何修改均由主要研究者完成并记录，并获得伦理委员会或监管机构的批准/赞成意见，

 

j) register the information of the clinical investigation in a publicly accessible database prior to recruitment of the first subject (see 5.4).

 

在招募第一个受试者之前，在一个公共数据库中登记临床研究的信息(见5.4)。

 

9.2.3. Conduct of clinical investigation临床研究实施

 

The sponsor shall be responsible for

 

申办者应负责：

 

a) accountability of investigational devices throughout the clinical investigation,

 

在整个临床研究中对研究器械进行管理，

 

b) documenting correspondence with all parties involved in the clinical investigation, including ECs and regulatory authorities,

 

记录与临床研究相关各方的沟通内容，包括伦理委员会和监管机构，

 

c) ensuring that the clinical investigation is appropriately monitored by determining the extent and nature of monitoring, including the strategy for source data verification, based on considerations such as the objective, design, complexity, size, critical data points and endpoints of the clinical investigation,

 

通过确定监查的范围和性质确保临床研究得到适当的监查，包括基于临床研究目的、设计、复杂性、规模、关键数据点和终点等因素的源数据核查策略，

 

d) ensuring that risk management activities are performed and documented (see 6.2 and 7.1),

 

确保执行风险管理活动并以予记录（参见6.2和7.1),

 

e) reviewing the monitoring report(s) and following up any action(s) required in the monitoring report(s) (see 9.2.4.7),

 

审查监查报告，并跟进监查报告中所需的任何行动（见9.2.4.7），

 

f) taking prompt action to secure compliance with all clinical investigation requirements,

 

迅速采取行动，确保符合所有临床研究的要求，

 

g) performing and documenting root cause analysis and implementation of appropriate corrective and preventive action if noncompliance significantly affects or has the potential to significantly affect subject protection or reliability of clinical investigation results,

 

如果不合规严重影响或可能严重影响受试者保护或临床研究结果的可靠性，需要进行根本原因分析并记录以实施适当的纠正和预防措施，

 

h) submitting progress reports after the data integrity is confirmed, including safety summary and deviations, when requested, to all reviewing ECs and the regulatory authorities.

 

在确认数据完整性后，当有要求时，应向所有伦理委员会和监管机构提交进度报告，包括安全总结和偏离。

 

9.2.4. Monitoring监查

 

9.2.4.1. General概述

 

Monitoring shall be conducted according to the monitoring plan (see 6.7).

 

应按照监查计划进行监查（见6.7）。

 

The purpose of clinical investigation monitoring is to verify that

 

临床研究监查的目的是为了确认

 

a) the rights, safety, and well-being of the human subjects are protected,

 

对人类受试者的权利、安全和福祉的保护，

 

b) the reported data are accurate, complete, and verifiable from source documents, and

 

报告的数据准确、完整，并可从源文件中得到确认，以及

 

c) the conduct of the clinical investigation complies with the approved CIP, subsequent amendment(s), this document, and the applicable regulatory requirement(s) and applicable requirements of the EC.

 

临床研究的进行符合批准的研究方案、后续修订、本文件、适用的监管要求、适用的伦理委员会要求。

 

9.2.4.2. Qualifications of the monitor监查员的资质

 

Monitors shall be

 

监查员应

 

a) qualified in the field of this document through training and experience as well as scientific or clinical knowledge,

 

通过培训，以及有科学和临床相关知识的经验以获得本文件所涉及的资格，

 

b) knowledgeable on the use of the investigational device(s) and relevant requirements, CIP, and informed consent process (see 5.8),

 

了解研究器械的使用和相关要求、研究方案、知情同意过程（见5.8），

 

c) trained on the sponsor's clinical quality management procedures relevant to monitoring activities as well as any special procedures for monitoring a specific clinical investigation.

 

培训内容包括与监查活动相关的申办者临床质量管理流程，以及监查特定临床研究中的任何特殊流程。

 

Training shall be documented in the sponsor's files.

 

培训应记录在申办者的文件中。

 

9.2.4.3. Assessment of the investigation site对研究中心评估

 

The monitor shall assess each investigation site to verify that the principal investigator has

 

监查员应评估每个研究中心，以核实主要研究者是否有

 

a) adequate qualifications,

 

足够的资质，

 

b) adequate resources, including facilities, laboratories, equipment, and a qualified investigation site team,

 

充足的资源，包括设施、实验室、设备和一个合格的研究团队，

 

c) access to an adequate number of subjects.

 

评估是否有足够的受试者数量。

 

9.2.4.4. Initiation of the investigation site研究中心启动

 

The monitor shall initiate each investigation site in accordance with the monitoring plan to ensure that the principal investigator and investigation site team

 

监查人员应根据监查计划启动每个研究中心，以确保主要研究员和研究中心团队

 

a) have received and understood the requirements and contents of

 

已经接收并了解以下要求和内容

 

1) the CIP,

 

临床研究计划

 

2) the IB,

 

研究者手册

 

3) the informed consent form,

 

知情同意书

 

4) the CRFs,

 

病例报告表

 

5) the instructions for use,

 

使用说明

 

6) any written clinical investigation agreements, as appropriate,

 

任何书面的临床研究协议，如必要，

 

b) have access to an adequate number of investigational devices,

 

能够获得足够数量的研究器械，

 

c) have been trained in the use of the investigational device,

 

接受过研究器械使用方面的培训，

 

d) are familiar with the responsibilities of the principal investigator, as described in Clause 10.

 

熟悉主要研究者的职责，如第10章节所述。

 

9.2.4.5. Routine monitoring visits常规监查访视

 

The monitor shall perform routine monitoring activities to verify that

 

监查员应执行常规监查活动以核实以下情况：

 

a) compliance with the CIP, any subsequent amendment(s), this document and regulatory requirements is maintained; deviations shall be discussed with the principal investigator(s) or authorized designee, documented and reported to the sponsor,

 

遵守研究方案、任何后续修订、本文件和监管要求；偏离应与主要研究者或授权指定人员讨论，并形成文件并报告给申办者，

 

b) only authorized members of the investigation site team, as described in 9.2.1 f), are participating in the clinical investigation,

 

只有9.2.1 f)所述的授权成员参与临床研究，

 

c) the investigational device and, where applicable, the comparator are used according to the CIP, IB or instructions for use and that, where modifications are required to the device, its method of use, or the CIP, these are reported to the sponsor,

 

研究器械，必要时也包括对照器械，根据研究方案、研究者手册或使用说明的要求使用，当需要对器械、其使用方法或研究方案进行修改时，这些将通报给申办者，

 

d) investigation site resources, including laboratories, equipment and the investigation site team, remain adequate throughout the duration of the clinical investigation,

 

研究中心资源，包括实验室、设备和研究团队，在整个临床研究过程中保证充足，

 

e) the principal investigator continues to have access to an adequate number of subjects and investigational devices,

 

主要研究者能够持续获得足够数量的受试者和研究器械，

 

f) signed and dated informed consent forms have been obtained from each subject or their legally designated representative before any clinical investigation-related procedures are undertaken,

 

在进行任何临床研究相关流程之前，已从每个受试者或其法定代表人处获得签署名字和注明日期的知情同意书，

 

g) source documents including the documentation of type and location, and other clinical investigation records are accurate, complete, up to date, stored, and maintained appropriately,

 

源文件，包括文件类型和位置，以及其他临床研究记录应准确、完整、及时、妥善地存储和维护，

 

h) CRFs and queries are complete, recorded in a timely manner, and consistent with source documents, and are consistent with the requirements in the CIP,

 

病例报告表和质疑表应及时记录并完成，与源文件一致，符合研究方案的要求，

 

i) appropriate corrections, additions or deletions are made to the CRFs, dated, explained if necessary and initialled by the principal investigator or by his/her authorized designee; the monitor shall not make corrections, additions, or deletions to the CRFs,

 

对病例报告表进行适当的更正、添加或删除应注明日期，必要时应解释原因，并由主要研究者或其授权指定人签字；监查员不得对病例报告表进行更正、添加或删除，

 

j) visits that the subjects fail to make, tests not conducted, or examinations not performed, as well as subjects withdrawn (including reason if available) are appropriately reported on the CRFs,

 

受试者未进行的随访、未进行测试或未进行检查，以及受试者退出（如果可能注明原因）适当地报告在病例报告表中，

 

k) all adverse events and device deficiencies are reported to the sponsor, and all serious adverse events and device deficiencies that could have led to a serious adverse device effect are reported to the sponsor without unjustified delay,

 

所有不良事件和器械缺陷都已经报告给申办者，所有可能导致器械相关严重不良反应的严重不良事件和器械缺陷都已经报告给申办者，且没有不合理的延迟，

 

l) serious adverse events and device deficiencies that could have led to a serious adverse device effect are reported to the EC and the regulatory authority, as required,

 

如需要，有可能导致器械相关严重不良反应的严重不良事件和器械缺陷都已经报告给伦理委员会和监管机构，

 

m) deviations (see 5.6.4 b)) are reported to the EC and can also be reported to the regulatory authority,

 

偏离（见5.6.4b)已经报告给伦理委员会，也同时报告给了监管机构，

 

NOTE：National regulations can also apply.

 

注：依据不同国家法规执行。

 

n) the storage and investigational device accountability are correct, and the traceability process is being followed and documented in the investigator’s files,

 

研究器械的储存和管理是正确的，可追溯过程并记录在研究者的文件中，

 

o) all required reports, notifications, applications, submissions and correspondence are maintained in the investigator's files and are accurate, complete, timely, legible, dated and identify the clinical investigation,

 

所有所需的报告、通知、申请、递交和通信都保存在研究者文件夹中，并且准确、完整、及时、清晰、注明日期以区别于不同的临床研究，

 

p) maintenance and calibration of the equipment relevant to the assessment of the clinical investigation is appropriately performed and documented, where applicable,

 

如必要，与临床研究评估相关设备的维护和校准被适当地执行并记录，

 

q) current laboratory normal values, laboratory certifications, accreditations, or other validations are present in the investigator's file, if required,

 

如需要，研究者文件夹中包含了当前的实验室正常值，实验室证书、认证或其他验证，

 

r) subject withdrawal has been documented; the monitor shall discuss this with the principal investigator or his/her authorized designee,

 

受试者退出已记录在案；监查员应与主要研究者或其授权指定人员讨论此情况，

 

s) subject non-compliance with the requirements stated in the informed consent has been documented; the monitor shall discuss this with the principal investigator or his/her authorized designee,

 

受试者不符合知情同意书中注明的要求已被记录下来；监查员应与主要研究者或其授权指定人员讨论此情况，

 

t) the principal investigator and investigation site team are informed and knowledgeable of all relevant document updates concerning the clinical investigation,

 

主要研究者和研究团队已经被告知并了解与临床研究相关的所有最新文件，

 

u) any corrective and preventive actions, as needed, have been implemented and are effective.

 

如需要，任何纠正和预防措施都已得到有效的实施。

 

9.2.4.6. Close-out activities关中心活动

 

The monitor shall perform close-out activities as described in Clause 8.

 

监查员应执行第8章节中所述的关中心活动。

 

9.2.4.7. Monitoring reports监查报告

 

Results of monitoring activities should be documented in sufficient detail to allow verification of compliance with the monitoring plan (see 6.7).

 

监查活动的结果应充分详细记录，以验证对监查计划的依从性（见6.7）。

 

All monitoring activities shall be documented and reported to the sponsor [see also 9.2.3 c)] and shall include

 

所有监查活动应记录并报告给申办者[参见9.2.3 c)]并应包括

 

a) the date, investigation site identification, name of the monitor and name of the principal investigator or other individuals contacted,

 

日期、研究中心编号、监查员姓名以及主要研究者或其他联系人员的姓名，

 

b) a summary of what the monitor reviewed and his/her observation(s) regarding the completion of previous action items, significant findings, facts, deviations, conclusions, and recommended actions to be taken to secure compliance.

 

监查员审查内容的摘要，以及他/她对之前工作内容的完成情况、重大发现、事实、偏离、结论，以及为确保合规而建议采取的行动。

 

A copy of the monitoring report or a summary of key findings shall be shared with the principal investigator in writing.

 

监查报告或重要发现的摘要的副本应以书面形式与主要研究者共享。

 

NOTE：The above requirements can also apply to clinical investigation-related communication(s) depending on sponsor procedures or national regulations.

 

注：上述要求也可适用于临床研究相关的交流，这具体取决于申办者流程或国家法规，

 

9.2.5. Safety evaluation and reporting安全评估和报告

 

The sponsor is responsible for the classification of adverse events and ongoing safety evaluation of the clinical investigation and shall

 

申办者负责不良事件的分类和对临床研究进行安全性评估，并应

 

a) review the investigator's assessment of all adverse events and determine and document in writing their seriousness and relationship to the investigational device and procedures required by the CIP; in case of disagreement between the sponsor and the principal investigator(s), the sponsor shall communicate both opinions to concerned parties, as defined in c), d), and e) given below,

 

审查研究者对所有不良事件的评估和决策，并以书面形式确定并记录其严重性，以及与研究器械和研究方案流程的相关性；如果申办者和主要研究者之间存在如下述c）、d）和e）所述的分歧时，申办者应向有关各方传达两种意见，

 

NOTE 1 Classification of adverse events and safety evaluation can be performed by an independent Clinical Events Committee (CEC) to mitigate the potential for bias and financial conflict.

 

注1：不良事件的分类和安全性评估可由一个独立的临床事件委员会(CEC)进行，以减轻潜在的偏倚和利益冲突。

 

b) review all device deficiencies and determine and document in writing whether they could have led to a serious adverse device effect; in case of disagreement between the sponsor and the principal investigator(s), the sponsor shall communicate both opinions to concerned parties, as defined in c), d), and e) given below,

 

审查所有器械缺陷和决策，确定并书面记录它们是否可能导致严重的器械不良反应；如果申办者和主要研究者之间存在如下述c）、d）和e）所述的分歧时，申办者应向有关各方传达两种意见，

 

c) report or ensure the reporting, to the EC by the principal investigator(s), of all serious adverse events and device deficiencies that could have led to a serious adverse device effect, if required by the CIP or by the EC,

 

如果研究方案或伦理委员会要求，主要研究者应向伦理委员会报告或正在报告所有可能导致器械相关严重不良反应的严重不良事件和器械缺陷，

 

NOTE 2 Certain national regulations can also apply.

 

注2：某些国家法规也可以适用。

 

d) report to regulatory authorities, within the required time period, all serious adverse events and device deficiencies that could have led to a serious adverse device effect, including serious health threat, if required by the CIP,

 

如果研究方案有要求，应在规定的时间段内，向监管机构报告所有可能导致器械相关严重不良反应的严重不良事件和器械缺陷，包括严重的健康威胁的情况，

 

NOTE 3 Certain national regulations can also apply.

 

注3：某些国家法规也可以适用。

 

e) report all relevant safety information to the DMC, if established, according to written procedures, 

 

如果已经建立标准操作流程，应向数据监查委员会报告所有相关的安全信息，

 

f) in the case of a multicentre clinical investigation, inform all principal investigators in writing of all the serious adverse events at all investigation sites that have been reported to the sponsor, and ensure that they are reported to their EC, if required by the CIP or by the EC, whichever is more stringent; this information shall be sent to all the principal investigators within a time frame established based on the perceived risk as defined in the risk assessment (analysis and evaluation),

 

在进行多中心临床研究时，以书面形式将所有研究中心已报告给申办者的所有严重不良事件通知给所有主要研究者，并确保这些事件已经报告给所在的伦理委员会（如果研究方案或伦理委员会有要求，以更严格的为准）；该信息应根据在风险评估（分析和评估）中定义的预知风险，在规定的时间内发送给所有主要研究者，

 

NOTE 4：Certain national regulations can also apply.

 

注4：某些国家法规也可以适用。

 

g) ensure that the EC and the regulatory authorities are informed of significant new information about the clinical investigation,

 

确认伦理委员会和监管机构被告知与临床研究相关的重要新信息，

 

h) in case of serious adverse device effects and device deficiencies that could have led to serious adverse device effects, determine whether the risk analysis needs to be updated and assess whether corrective or preventive action is required.

 

如果严重不良事件和器械缺陷可能导致严重的器械不良反应，确认是否需要更新风险分析并评估是否采取纠正或预防措施

 

9.2.6. Clinical investigation close-out临床研究关闭

 

The sponsor shall

 

申办者应

 

a) ensure all clinical investigation close-out activities are properly conducted as described in Clause 8,

 

确保所有临床研究收尾活动按照第8章节的规定正确进行，

 

b) perform a statistical analysis of the data,

 

并对其进行数据统计分析，

 

c) produce a clinical investigation report and submit it for review, as described in 8.4,

 

制作临床研究报告并提交审查，如8.4所述，

 

d) ensure that the clinical investigation report, whether for a completed or prematurely terminated clinical investigation, is provided to the EC, participating investigators and regulatory authorities,

 

确保临床研究报告，无论是一个已完成或提前终止的临床研究，已经提供给伦理委员会、参考的研究者以及监管机构，

 

NOTE：National regulations can also apply.

 

注：国家法规也可以适用。

 

e) update publicly accessible database with clinical investigation results, if applicable (see 5.4).

 

如果适用，将临床研究结果更新至公开访问的数据库（参见5.4）。

 

9.3.Outsourcing of duties and functions职责和职能的外包

 

The sponsor may transfer any or all of the duties and functions related to the clinical investigation, including monitoring, to an external organization (such as a CRO or individual contractor), but the ultimate responsibility for the quality and integrity of the clinical investigation conduct shall reside with the sponsor. The sponsor shall ensure oversight of any clinical investigation-related duties and functions.

 

申办者可将部分或所有与临床研究相关的职责和职能，包括监查，移交给外部组织(如，CRO或个人承包商)，但对临床研究的质量和完整性申办者应承担最终责任。申办者应确保对任何与临床研究相关的职责和职能进行监督。

 

The outsourcing of duties or functions to external organizations, including subcontractors of the sponsor’s CRO(s), shall be addressed by the sponsor in accordance with written procedures for the control of suppliers. The sponsor shall specify in writing any clinical investigation-related duty or function assumed by the external organization, retaining any clinical investigation-related duties and functions not specifically transferred to, and assumed by, the external organization. Records of transfer of duties and functions shall be maintained.

 

将职责或职能外包给外部组织时，包括申办者自己管理CRO业务的分包商，应由申办者按照供应商质控标准操作流程进行处理。申办者应以书面形式确定由外部组织承担的任何与临床研究相关的职责或职能，并保留没有特别转移给外部组织，也没有由外部组织承担的任何与临床研究相关的职责和职能。应保存职责和职能转移的记录。

 

The sponsor shall be responsible for verifying the existence of and adherence to written procedures at the external organization.

 

申办者应负责验证外部组织是否存在并遵守标准操作流程。

 

All requirements in this document applying to a sponsor shall also apply to the external organization in as much as this organization assumes the clinical investigation-related duties and functions of the sponsor.

 

本文件中适用于申办者的所有要求，也应适用于外部组织，该组织承担与申办者一样的临床研究相关职责和职能。

 

9.4.Communication with regulatory authorities与监管机构沟通

 

The sponsor shall, if required,

 

如需要，申办者应，

 

a) notify or obtain approval/non-objection from regulatory authorities in the country where the clinical investigation is conducted,

 

被通知或获得临床研究所在国监管机构的批准/赞同，

 

b) notify or obtain approval/non-objection from regulatory authorities in the country where the clinical investigation is conducted on any amendments of documents already reviewed by these authorities before these amendments are applied,

 

在执行相关相关修订之前，监管机构已经对修改文件进行过审阅，并被通知或获得临床研究所在国监管机构的批准/赞同，

 

c) report on the progress and status of the clinical investigation,

 

报告临床研究的进展和现状，

 

d) perform safety reporting as specified in 9.2.5,

 

按照9.2.5中的规定执行安全报告，

 

e) report any occurrence of withdrawing the investigational devices from the investigation site for reasons related to safety of the subject or investigational device clinical performance.

 

报告因受试者安全性或研究器械性能从研究中心撤回研究器械的事件。

 

10.Responsibilities of the principal investigator主要研究者的职责

 

10.1.General概述

 

The role of the principal investigator is to implement, oversee the management of the day-to-day conduct of the clinical investigation as well as ensure data integrity and the rights, safety, and well- being of the subjects involved in the clinical investigation.

 

主要研究者的职责是实施并对临床研究进行日常监督管理，以确保数据的完整性和参与临床研究的受试者的权利、安全和福祉。

 

The principal investigator is responsible for ensuring adequate training and qualification of the investigation site team and for maintaining oversight of their activities. The principal investigator may delegate tasks to qualified members of the investigation site team but retains responsibility for the clinical investigation (see also 7.6). This also applies when activities are outsourced to an external organization by the principal investigator in which case he/she shall implement procedures to ensure the integrity of all tasks performed and any data generated by this external organization.

 

主要研究者负责确认研究中心团队的资格并使其得到充分培训，同时持续对其活动进行监督。主要研究者可以将任务委托给研究中心团队中有资质的成员，但保留对临床研究的责任（另见7.6）。这也适用于当主要研究者将研究外包给外部组织时，在这种情况下，他/她应执行相关流程以确保外部组织对所有任务执行和数据生成的完整性。

 

10.2.Qualification of the principal investigator主要研究者的资格

 

The principal investigator shall

 

主要研究者应

 

a) be qualified by education, training, and experience to assume responsibility for the proper conduct of the clinical investigation in accordance with this document; evidence of such qualifications of the principal investigator shall be provided to the sponsor through up-to-date CVs or other relevant documentation,

 

有相应的教育、培训和经验，根据本文件可以承担临床研究实施的责任；主要研究员的资格证明应通过最新的简历或其他相关文件向申办者提供，

 

NOTE：National regulations can also apply.

 

注：国家法规也可以适用。

 

b) be experienced in the field of application and trained in the use of the investigational device under consideration,

 

在相关应用领域有经验，是否接受过研究器械使用培训应考虑在内，

 

c) disclose potential conflicts of interest, including financial, that can interfere with the conduct of the clinical investigation or interpretation of results, and

 

披露可能，包括财务冲突，会干扰临床研究或结果解释的利益冲突，以及

 

d) be knowledgeable with the method of obtaining informed consent.

 

了解获取知情同意的方法。

 

10.3.Qualification of investigation site研究中心的资格

 

The principal investigator shall be able to demonstrate that the proposed investigation site

 

主要研究者应能够证明拟参研的研究中心

 

a) has the required number of eligible subjects needed within the agreed recruitment period,

 

在约定的招募期内，有所需数量的合格受试者，

 

b) has an investigation site team that is: qualified by education, training, and experience to assume responsibility for the prope conduct of the clinical investigation in accordance with this document; evidence of such qualifications for members of the investigation site team shall be documented through up-to-date CVs or other relevant documentation,

 

有相应教育、培训和经验的研究团队可以根据本文件承担临床研究实施的责任；研究团队的资格证明应通过最新的简历或其他相关文件向申办者提供，

 

NOTE：National regulations can also apply.

 

注：国家法规也可以适用。

 

c) has adequate facilities.

 

有足够的设施。

 

10.4.Communication with the EC与伦理委员会沟通

 

The principal investigator shall

 

主要研究者应

 

a) provide the sponsor with copies of any clinical investigation-related communications between the principal investigator and the EC, comply with the requirements described in 5.6,

 

向申办者提供主要研究者和伦理委员会之间任何临床研究相关沟通内容的副本，并遵守5.6中所述的要求，

 

b) obtain the written and dated approval/favourable opinion of the EC for the clinical investigation, and ensure that regulatory authority approval is provided by the sponsor and communicated to the EC where required, before recruiting subjects and implementing all subsequent amendments, if required,

 

如需要，在招募受试者并实施所有后续修订之前，获得伦理委员会对临床研究的书面批准/赞同意见，并确保申办者已经得到监管机构的批准，并在必要时通知伦理委员会，

 

c) perform safety reporting as specified in 10.8 (for adverse event categorization, see Annex F),

 

按照10.8中规定进行安全报告(不良事件分类见附件F)，

 

d) promptly report any deviations from the CIP that affect the rights, safety or well-being of the subject or the scientific integrity of the clinical investigation, including those which occur under emergency circumstances, if required by the EC or the CIP,

 

及时报告任何影响受试者权利、安全、福祉，或临床研究科学完整性的研究方案偏离，包括在紧急情况下发生的研究方案偏离，

 

NOTE：National regulations can also apply.

 

注：国家法规也可以适用。

 

e) notify suspension, premature termination, or routine close-out of the clinical investigation as described in Clause 8.

 

依据第8章节通知临床研究的暂停、提前结束或常规关中心。

 

In particular circumstances, the communication with the EC can be performed by the sponsor, partly or in full, in which case the sponsor shall keep the principal investigator informed.

 

在特殊情况下，申办者可以部分或全部与伦理委员会进行的沟通，在这种情况下，申办者应随时通知主要研究者。

 

10.5.Informed consent process知情同意过程

 

The principal investigator shall

 

主要研究者应

 

a) comply with the requirements specified in 5.8,

 

遵从5.8节所述的要求，

 

b) ensure compliance with ethical principles for the process of obtaining informed consent, and

 

确保在获得知情同意的过程中遵守伦理原则，以及

 

c) ensure and document appropriate training if an authorized designee is appointed to conduct the informed consent process.

 

如果指定授权指定人员执行知情同意过程，确保进行适当的培训并记录。

 

NOTE：Regulatory requirements can apply.

 

注：国家法规也可以适用。

 

10.6.Compliance with the CIP临床研究计划的依从性

 

The principal investigator shall

 

主要研究者应

 

a) indicate his/her acceptance of the CIP in writing,

 

以书面形式确认其认可临床研究计划，

 

b) conduct the clinical investigation in compliance with the CIP,

 

依据临床研究计划执行临床研究，

 

c) create and maintain source documents throughout the clinical investigation and make them available as requested during monitoring visits or audits as well as maintain documentation of the type and location of these source documents,

 

在整个临床研究过程中创建和维护源文件，并在监查访视或稽查期间根据要求提供这些文件，并维护该文件的类型和这些源文件的位置，

 

d) ensure that the investigational device is used solely by authorized users as specified in 7.2, and in accordance with the CIP and instructions for use,

 

确保研究器械仅由7.2节定义的经授权的用户，并依从临床研究计划和说明使用的要求使用，

 

e) propose to the sponsor any appropriate modification(s) of the CIP or investigational device or of the use of the investigational device,

 

向申办者建议对临床研究计划，或研究器械，或研究器械的使用进行任何适当的修改，

 

f) refrain from implementing any modifications to the CIP without agreement from the sponsor, EC and regulatory authorities, if required,

 

如必要，在未经申办者、伦理委员会和监管机构同意的情况下，不得对临床研究计划进行任何修改，

 

g) document and explain any deviation from the approved CIP that occurred during the course of the clinical investigation,

 

记录并解释在临床研究过程中发生的任何与已批准的临床研究计划有关的偏离，

 

h) ensure that an adequate investigation site team and facilities exist and are maintained and documented during the clinical investigation,

 

确保有足够的研究团队和设施，并在临床研究期间得到维护和记录，

 

i) ensure that maintenance and calibration of the equipment relevant for the assessment of the clinical investigation is appropriately performed and documented, where applicable,

 

确保与临床研究评估相关设备的维护和校准得到适当的执行和记录，如适用，

 

j) ensure the accuracy, completeness, legibility and timeliness of the data reported to the sponsor in the CRFs and in all required reports,

 

确保在病例报告表和所有要求报告给申办者的数据是准确性、完整性、可读性和及时性，

 

k) maintain the device accountability records,

 

维护器械的管理记录

 

l) comply with the procedure for the safe return of investigational devices including potentially hazardous devices, and in case of reported device deficiencies, collaborate with the sponsor to provide the necessary information allowing an accurate analysis where appropriate,

 

遵守安全返还研究器械的流程，包括有潜在危险的器械。如果报告器械缺陷，与申办者一道提供必要的信息，以便在适当情况下进行准确分析，

 

m) allow and support the sponsor to perform monitoring and auditing activities,

 

允许并支持申办者执行监查和稽查活动，

 

n) be accessible to the monitor and respond to questions during monitoring visits,

 

在监查访视期间，能够与监查员接触并回答问题，

 

o) determine the cause and implement appropriate corrective and preventive actions to address significant noncompliance,

 

确定原因并实施适当的纠正和预防措施，以解决重要的不合规问题，

 

p) allow and support regulatory authorities and the EC when performing auditing activities,

 

允许并支持监管机构和伦理委员会执行稽查活动，

 

q) ensure that all clinical investigation-related records are retained as specified in 8.3,

 

确保所有临床研究相关记录保存按照8.3的规定执行，

 

r) sign the clinical investigation report, as specified in 8.4.

 

按照8.4中的规定签署临床研究报告。

 

10.7.Medical care of subjects受试者的医疗保健

 

The principal investigator shall

 

主要研究者应

 

a) provide adequate medical care to a subject during and after a subject's participation in a clinical investigation in the case of adverse events, as described in the informed consent,

 

如知情同意书所述，当受试者出现不良事件时，应在受试者参与临床研究期间和之后，向受试者提供充分的医疗保健，

 

b) inform the subject of the nature and possible cause of any adverse events experienced,

 

告知受试者的任何可能引起的不良事件的性质和原因，

 

c) provide the subject with the necessary instructions on proper use, handling, storage and return of the investigational device, when it is used or operated by the subject,

 

当由受试者使用或操作研究器械时，应向受试者提供关于正确使用、处理、储存和归还研究器械的必要说明，

 

d) inform the subject of any new significant findings occurring during the clinical investigation, including the need for additional medical care that can be required,

 

告知受试者在临床研究过程中发现的任何新的重要发现，包括是否需要额外的医疗保健，

 

e) provide the subject with well-defined procedures for possible emergency situations related to the clinical investigation, and make the necessary arrangements for emergency treatment, including decoding procedures for blinded/masked clinical investigations, as needed,

 

为受试者提供与临床研究相关的可能的紧急情况时的明确操作流程，并为紧急治疗做出必要的安排，包括盲态临床研究的揭盲流程，

 

f) ensure that clinical records are clearly marked to indicate that the subject is enrolled in a particular clinical investigation,

 

确保临床记录清晰以表明受试者参加了某一特定的临床研究，

 

g) if appropriate, provide subjects enrolled in the clinical investigation with some means of showing their participation, together with identification and compliance information for concomitant treatment measures (contact address and telephone numbers shall be provided),

 

如果适用，提供临床研究招募受试者的方法，以及伴随治疗措施的确认和依从性（应提供联系地址和电话号码），

 

h) inform, with the subject's approval the subject's personal physician about the subject's participation in the clinical investigation,

 

在受试者同意的情况下，告知受试者的私人医生受试者参与临床研究的情况，

 

NOTE：National regulations can apply.

 

注：国家法规也可以适用。

 

i) make all reasonable efforts to ascertain the reason(s) for a subject's premature withdrawal from the clinical investigation while fully respecting the subject's rights.

 

在充分尊重受试者的意见的同时，尽一切合理的努力来确定受试者提前退出临床研究的原因。

 

10.8.Safety reporting安全性报告

 

The principal investigator shall

 

主要研究者应

 

a) record every adverse event and observed device deficiency, together with an assessment (adverse event categorization, see Annex F),

 

记录每一个不良事件和观察到的器械缺陷，并进行评估（不良事件分类，见附件F），

 

b) report to the sponsor, without unjustified delay, all serious adverse events and device deficiencies that could have led to a serious adverse device effect; this information shall be promptly followed by detailed written reports, as specified in the CIP,

 

在没有合理延期的情况下，应向申办者报告所有可能导致严重的器械不良反应的严重不良事件和器械缺陷；应及时提供这些信息的详细书面报告，如临床研究计划中的规定，

 

c) report to the EC serious adverse events and device deficiencies that could have led to a serious adverse device effect, if required by the CIP or by the EC,

 

如果临床研究计划或伦理委员会有要求，应向伦理委员会报告可能导致器械相关严重不良反应的严重不良事件和器械缺陷，

 

NOTE 1：National regulations can also apply.

 

注：国家法规也可以适用。

 

d) report to regulatory authorities serious adverse events and device deficiencies that could have led to a serious adverse device effect,

 

向监管机构报告可能导致器械相关严重不良反应的严重不良事件和器械缺陷，

 

NOTE 2：National regulations can apply.

 

注：国家法规也可以适用。

 

e) supply the sponsor, upon sponsor's request, with any additional information related to the safety reporting of a particular event.

 

根据申办者的要求，向其提供与特定安全性事件报告相关的任何额外信息。