中文字幕一级黄色A级片|免费特级毛片。性欧美日本|偷拍亚洲欧美1级片|成人黄色中文小说网|A级片视频在线观看|老司机网址在线观看|免费一级无码激情黄所|欧美三级片区精品网站999|日韩av超碰日本青青草成人|一区二区亚洲AV婷婷

INTERNATIONAL STANDARD 國際標(biāo)準(zhǔn) ISO 14155

Third edition 第三版 2020-07

 

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

 

人類受試者的醫(yī)療器械臨床研究——良好的臨床實(shí)踐

 

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

 

Contents目錄

Foreword前言

 

Clinical investigation of medical devices for human subjects — Good clinical practice人類受試者的醫(yī)療器械臨床研究-良好的臨床實(shí)踐

 

1. Scope范圍

 

2. Normative references引用標(biāo)準(zhǔn)

 

3. Terms and definitions術(shù)語和定義

 

4. Summary of good clinical practice (GCP) principles良好臨床實(shí)踐(GCP)原則概述

 

5. Ethical considerations倫理考慮

 

5.1. General概述

 

5.2. Improper influence or inducement不當(dāng)影響或誘導(dǎo)

 

5.3. Compensation and additional health care補(bǔ)償和額外的醫(yī)療保健

 

5.4. Registration in publicly accessible database在公共可訪問數(shù)據(jù)庫中注冊

 

5.5. Responsibilities責(zé)任

 

5.6. Communication with the ethics committee (EC)與倫理委員會(huì)的溝通

 

5.7. Vulnerable populations弱勢人群

 

5.8. Informed consent知情同意

 

6. Clinical investigation planning臨床研究計(jì)劃

 

6.1. General概述

 

6.2. Risk management風(fēng)險(xiǎn)管理

 

6.3. Justification for the design of the clinical investigation臨床研究設(shè)計(jì)的合理性

 

6.4. Clinical investigation plan (CIP)臨床研究計(jì)劃

 

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

 

6.6. Case report forms (CRFs)病例報(bào)告表

 

6.7. Monitoring plan監(jiān)查計(jì)劃

 

6.8. Investigation site selection研究中心選擇

 

6.9. Agreement(s)協(xié)議

 

6.10. Labelling標(biāo)簽

 

6.11. Data monitoring committee (DMC)數(shù)據(jù)監(jiān)查委員會(huì)

 

7. Clinical investigation conduct臨床研究實(shí)施

 

7.1. General概述

 

7.2. Investigation site initiation研究中心啟動(dòng)

 

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臨床研究文件和文檔

 

7.6. Additional members of the investigation site team研究中心小組的額外成員

 

7.7. Subject privacy and confidentiality of data受試者隱私和數(shù)據(jù)保密

 

7.8. Document and data control文件和數(shù)據(jù)控制

 

7.9. Investigational device accountability研究器械管理

 

7.10. Accounting for subjects受試者審查

 

7.11. Auditing稽查

 

8. Suspension, termination, and close-out of the clinical investigation暫停、終止和結(jié)束臨床研究

 

8.1. Completion of the clinical investigation完成臨床試驗(yàn)

 

8.2. Suspension or premature termination of the clinical investigation暫停或提前終止臨床研究

 

8.3. Routine close-out常規(guī)關(guān)中心

 

8.4. Clinical investigation report臨床研究報(bào)告

 

8.5. Risk assessment and conclusions風(fēng)險(xiǎn)評(píng)估和結(jié)論

 

8.6. Document retention文件保存

 

9. Responsibilities of the sponsor申辦者的職責(zé)

 

9.1. Clinical quality management臨床質(zhì)量管

 

9.2. Clinical investigation planning and conduct臨床研究的計(jì)劃和實(shí)施

 

9.3. Outsourcing of duties and functions職責(zé)和職能的外包

 

9.4. Communication with regulatory authorities與監(jiān)管機(jī)構(gòu)溝通

 

10. Responsibilities of the principal investigator主要研究者的職責(zé)

 

10.1. General概述

 

10.2. Qualification of the principal investigator主要研究者的資格

 

10.3. Qualification of investigation site研究中心的資格

 

10.4. Communication with the EC與倫理委員會(huì)溝通

 

10.5. Informed consent process知情同意過程

 

10.6. Compliance with the CIP研究方案的依從性

 

10.7. Medical care of subjects受試者的醫(yī)療保健

 

10.8. Safety reporting安全性報(bào)告

 

Annex A Clinical investigation plan (CIP) 附件A臨床研究計(jì)劃

 

A.1. General概述

 

A.1.1. Introduction介紹

 

A.1.2. Identification of the clinical investigation plan臨床研究計(jì)劃的識(shí)別信息

 

A.1.3. Sponsor申辦者

 

A.1.4. Principal investigator, coordinating investigator and investigation site(s)主要研究者，協(xié)調(diào)研究員和研究中心

 

A.1.5. Overall synopsis of the clinical investigation臨床研究的總體摘要

 

A.2. Identification and description of the investigational device研究器械的識(shí)別和描述

 

A.3. Justification for the design of the clinical investigation臨床研究設(shè)計(jì)的合理性

 

A.4. Benefits and risks of the investigational device, clinical procedure, and clinical investigation試驗(yàn)器械、臨床流程和臨床研究的受益和風(fēng)險(xiǎn)

 

A.5. Objectives and hypotheses of the clinical investigation臨床研究的目的和假設(shè)

 

A.6. Design of the clinical investigation臨床研究設(shè)計(jì)

 

A.6.1. General概述

 

A.6.2. Investigational device(s) and comparator(s)研究器械和對(duì)照產(chǎn)品

 

A.6.3. Subjects受試者

 

A.6.4. Procedures流程

 

A.6.5. Monitoring plan監(jiān)查計(jì)劃

 

A.7. Statistical design and analysis統(tǒng)計(jì)設(shè)計(jì)和計(jì)劃

 

A.8. Data management數(shù)據(jù)管理

 

A.9. Amendments to the CIP臨床研究計(jì)劃的修訂

 

A.10. Deviations from clinical investigation plan臨床研究計(jì)劃的偏離

 

A.11. Device accountability器械管理

 

A.12. Statements of compliance合規(guī)性聲明

 

A.13. Informed consent process知情同意過程

 

A.14. Adverse events, adverse device effects, and device deficiencies不良事件、器械不良反應(yīng)和器械缺陷

 

A.15. Vulnerable population (if applicable)弱勢人群（如適用）

 

A.16. Suspension or premature termination of the clinical investigation暫停或提前中止臨床研究

 

A.17. Publication policy出版政策

 

A.18. Bibliography參考文獻(xiàn)

 

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

 

B.1. General概述

 

B.1.1. Introduction介紹

 

B.1.2. Identification of the IB研究者手冊的識(shí)別信息

 

B.1.3. Sponsor/manufacturer申辦者/制造商

 

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

 

B.3. Preclinical testing臨床前測試

 

B.4. Existing clinical data現(xiàn)有的臨床數(shù)據(jù)

 

B.5. Risk management of the investigational device研究器械的風(fēng)險(xiǎn)管理

 

B.6. Regulatory and other references法規(guī)和其他參考

 

Annex C Case report forms (CRFs) 附件C 病例報(bào)告表

 

C.1 General概述105

 

C.2 Content and format內(nèi)容與格式

 

C.2.1 Overall considerations總體考慮

 

C.2.2 Cover page/login screen封面/登錄界面

 

C.2.3 Header or footer/e-CRF identifier頁眉或頁腳/電子病例報(bào)告表的標(biāo)識(shí)符

 

C.2.4 Types of CRF病例報(bào)告表形式

 

C.3 Procedural issues發(fā)布流程

 

Annex D Clinical investigation report 附件D 臨床研究報(bào)告

 

D.1 General概述

 

D.2 Cover page封面

 

D.3 Table of contents目錄內(nèi)容

 

D.4 Summary概要

 

D.5 Introduction介紹

 

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)臨床研究計(jì)劃

 

D.7 Results結(jié)果

 

D.8 Discussion and overall conclusions討論與結(jié)論

 

D.9 Abbreviated terms and definitions縮寫的術(shù)語和定義

 

D.10 Ethics倫理

 

D.11 Investigators and administrative structure of clinical investigation臨床研究的研究者和管理結(jié)構(gòu)

 

D.12 Signature page簽單頁

 

D.13 Annexes to the report報(bào)告附件

 

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

 

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

 

Annex G EC responsibilities 附件G倫理委員會(huì)職責(zé)

 

G.1 General概述

 

G.2 Responsibilities職責(zé)

 

G.3 Composition, functions, and operations組成、功能和實(shí)施

 

G.4 Information needed所需信息

 

G.5 Procedures流程

 

G.6 EC approval/favourable opinion letters倫理委員會(huì)批準(zhǔn)/贊同意見函

 

G.7 Records記錄

 

Annex H Application of ISO 14971 to clinical investigations  附件H ISO14971在臨床研究中的應(yīng)用

 

Annex I Clinical development stages 附件I 臨床研發(fā)階段

 

I.1 Background背景

 

I.2 Regulatory status監(jiān)管狀態(tài)

 

I.2.1 General概述

 

I.2.2 Pre-market clinical investigation上市前臨床研究

 

I.2.3 Post-market clinical investigation上市后臨床研究

 

I.3 Clinical development stages臨床研究階段

 

I.3.1 General概述

 

I.3.2 Pilot stage預(yù)試驗(yàn)階段

 

I.3.3 Pivotal stage關(guān)鍵性階段

 

I.3.4 Post-market stage上市后階段

 

I.4 Type of clinical investigation design臨床研究設(shè)計(jì)類型

 

I.4.1 General概述148

 

I.4.2 Exploratory clinical investigation探索性臨床研究

 

I.4.3 Confirmatory clinical investigation驗(yàn)證性臨床研究

 

I.4.4 Observational clinical investigation觀察性研究

 

I.5 Descriptors of clinical investigations臨床研究名詞解釋

 

I.5.1 General概述

 

I.5.2 First in human clinical investigation人類首次臨床研究

 

I.5.3 Early feasibility clinical investigation早期可行性臨床研究

 

I.5.4 Traditional feasibility clinical investigation傳統(tǒng)的可行性臨床研究

 

I.5.5 Pivotal clinical investigation關(guān)鍵性臨床研究

 

I.5.6 Registry注冊研究

 

I.6 Burden to subjects受試者負(fù)擔(dān)

 

I.6.1 General概述

 

I.6.2 Interventional clinical investigation干預(yù)性臨床研究

 

I.6.3 Non-interventional clinical investigation非干預(yù)性臨床研究

 

I.7 Applicability of this document’s principles本文件原則的適用性

 

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

 

J.1 General概述

 

J.2 Sponsor申辦者

 

J.3 Investigation site研究中心

 

Bibliography.

 

7.Clinical investigation conduct臨床研究實(shí)施

 

7.1.General概述

 

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

 

臨床研究應(yīng)按照臨床研究計(jì)劃的要求進(jìn)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.

 

臨床研究必須收到倫理委員會(huì)的書面批準(zhǔn)/贊同意見才能開始，如果需要，在臨床研究前由國家的監(jiān)管機(jī)構(gòu)進(jìn)行審查。

 

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).

 

申辦者應(yīng)確保在整個(gè)臨床研究過程中持續(xù)進(jìn)行風(fēng)險(xiǎn)管理，并考慮到與研究器械、臨床研究計(jì)劃要求的臨床流程和研究過程相關(guān)的所有方面（見6.2和7.4.4）。

 

7.2.Investigation site initiation研究中心啟動(dòng)

 

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.

 

在臨床研究開始時(shí)，申辦者或監(jiān)查員執(zhí)行并記錄每家研究中心的首次訪視或研究者會(huì)議（見9.2.4.4）。應(yīng)創(chuàng)建一個(gè)日志用于識(shí)別主要研究員和研究中心小組成員的姓名、首字母、簽名、職責(zé)和授權(quán)。

 

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：根據(jù)臨床研究的類型、復(fù)雜性及其相關(guān)風(fēng)險(xiǎn)，根據(jù)基于風(fēng)險(xiǎn)的監(jiān)查計(jì)劃的規(guī)定，可以通過電話或其他通信方式進(jìn)行現(xiàn)場啟動(dòng)。

 

7.3.Investigation site monitoring研究中心監(jiān)查

 

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

 

臨床研究的實(shí)施應(yīng)按照監(jiān)查計(jì)劃（見6.7和9.2.4）。

 

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

 

應(yīng)記錄所有監(jiān)查活動(dòng)（現(xiàn)場監(jiān)查見9.2.4.7）的結(jié)果。

 

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

 

7.4.1. Signals requiring immediate action需要立即采取行動(dòng)的信號(hào)

 

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.

 

申辦者或主要研究者可能會(huì)發(fā)現(xiàn)需要由申辦者進(jìn)行評(píng)估的嚴(yán)重威脅健康的不良事件或器械缺陷信號(hào)。

 

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

 

根據(jù)9.2.5中規(guī)定的監(jiān)管要求，任何嚴(yán)重威脅健康的事件都需要特定的報(bào)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).

 

在整個(gè)臨床研究過程中，所有不良事件和有關(guān)這些事件的任何新信息都應(yīng)及時(shí)記錄下來，并應(yīng)按照9.2.5和10.8的規(guī)定進(jìn)行報(bào)告(不良事件分類見附件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：這包括臨床研究計(jì)劃中確定的對(duì)臨床研究結(jié)果評(píng)估至關(guān)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：考慮到數(shù)據(jù)隱私法規(guī)，與用戶或其他人的不良事件可以同與受試者相關(guān)的不良事件分開記錄(參見 7.7).

 

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

 

注3：某些國家特定法規(guī)可適用于上市后臨床研究中的不良事件報(bào)告。

 

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

 

所有不良事件均應(yīng)在臨床研究的中期或最終報(bào)告中進(jìn)行報(bào)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應(yīng)記錄，并由申辦者按照控制不合格產(chǎn)品的標(biāo)準(zhǔn)操作流程進(jìn)行管理。申辦者應(yīng)在合適的情況下采取適當(dāng)?shù)募m正和預(yù)防措施，以保護(hù)受試者、使用者和其他人的安全。如果適用，對(duì)照器械的器械缺陷也應(yīng)記錄。

 

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

 

申辦者應(yīng)安排與器械缺陷相關(guān)的研究器械的召回（見7.9）。

 

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

 

未導(dǎo)致不良事件但可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的器械缺陷

 

a) if either suitable action had not been taken,

 

如果沒有采取適當(dāng)?shù)男袆?dòng)，

 

b) if intervention had not been made, or

 

如果沒有進(jìn)行干預(yù)，或者

 

c) if circumstances had been less fortunate,

 

如果情況不那么幸運(yùn)，

 

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.

 

應(yīng)按照9.2.5和10.8中的規(guī)定進(jìn)行報(bào)告。在適當(dāng)?shù)那闆r下，對(duì)已使用或植入的研究器械的分析應(yīng)作為支持性信息納入其中。

 

7.4.4. Risk assessment process for potentially unacceptable risks對(duì)潛在不可接受風(fēng)險(xiǎn)的風(fēng)險(xiǎn)評(píng)估過程

 

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

 

臨床研究過程中產(chǎn)生的風(fēng)險(xiǎn)應(yīng)按以下方式進(jìn)行管理（見圖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.

 

當(dāng)任何個(gè)人發(fā)現(xiàn)可能影響受試者、用戶或其他人安全的事件或信息時(shí)，都有義務(wù)告知所涉及的主要研究者和申辦者。

 

b) Risks are monitored against established risk acceptability thresholds.

 

根據(jù)已建立的風(fēng)險(xiǎn)可接受性閾值來監(jiān)測風(fēng)險(xiǎn)。

 

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.

 

當(dāng)發(fā)現(xiàn)有問題的情況時(shí)，申辦者應(yīng)與主要研究者并在適當(dāng)情況下與其他顧問協(xié)商，進(jìn)行初步風(fēng)險(xiǎn)分析。初步風(fēng)險(xiǎn)分析可能導(dǎo)致以下結(jié)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.

 

現(xiàn)有風(fēng)險(xiǎn)評(píng)估充分反映了新情況，受試者、使用者或其他人的個(gè)人和群體剩余風(fēng)險(xiǎn)仍然可以接受。申辦者應(yīng)確保記錄在臨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.

 

在可能的情況下，發(fā)現(xiàn)不可接受的風(fēng)險(xiǎn)或嚴(yán)重威脅健康時(shí)，申辦者應(yīng)立即暫停臨床研究，初步風(fēng)險(xiǎn)分析應(yīng)記錄在案，并按照8.2.1的要求通知相關(guān)方，同時(shí)進(jìn)行進(jìn)一步調(diào)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).

 

如果初步風(fēng)險(xiǎn)分析確認(rèn)可能存在不可接受的風(fēng)險(xiǎn)，申辦者應(yīng)根據(jù)ISO 14971進(jìn)行全面風(fēng)險(xiǎn)評(píng)估。在適當(dāng)?shù)那闆r下，數(shù)據(jù)監(jiān)查委員會(huì)或?qū)＜翌檰枒?yīng)對(duì)風(fēng)險(xiǎn)評(píng)估進(jìn)行分析或評(píng)估(見 8.2.1).

 

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

 

全面的風(fēng)險(xiǎn)評(píng)估可導(dǎo)致以下結(jié)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現(xiàn)有的風(fēng)險(xiǎn)評(píng)估中，對(duì)受試者、使用者或其他人的個(gè)人和群體剩余風(fēng)險(xiǎn)仍可接受。申辦者應(yīng)確保記錄在臨床研究文件中的合理性，并在恢復(fù)臨床研究前進(jìn)行必要的動(dòng)作(見 8.2.2).

 

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

 

可以采取糾正措施，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;

 

如果糾正措施不影響臨床研究的有效性，申辦者重新審視受益-風(fēng)險(xiǎn)分析，以證明繼續(xù)進(jìn)行臨床研究的合理性；在恢復(fù)臨床研究前進(jìn)行必要的活動(dòng)（見 8.2.2)；對(duì)臨床研究文件的影響見圖H.1。

 

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

 

如果糾正措施影響臨床研究的有效性，臨床研究應(yīng)終止。

 

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

 

如果不能采取糾正措施，臨床研究應(yīng)終止。

 

7.5.Clinical investigation documents and documentation臨床研究文件和文檔

 

7.5.1. Amendments修訂

 

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.

 

研究者手冊、臨床研究計(jì)劃、病例報(bào)告表、知情同意書和其他受試者信息，或其他臨床研究文件，如使用說明書，應(yīng)根據(jù)文件和文件變更版本控制要求，在整個(gè)臨床研究過程中根據(jù)需要進(jìn)行修訂。

 

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.

 

變更文件應(yīng)包括變更的描述、變更的理由及其對(duì)性能、有效性、安全性或其他終點(diǎn)的潛在影響，以及受影響文件的識(shí)別。

 

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.

 

除非另有特別規(guī)定，提出對(duì)臨床研究計(jì)劃修訂應(yīng)根據(jù)6.4中規(guī)定的交由相關(guān)各方進(jìn)行審查和批準(zhǔn)。如有需要，臨床研究計(jì)劃和受試者知情同意書的修訂應(yīng)通知倫理委員會(huì)或監(jiān)管機(jī)構(gòu)，或由其批準(zhǔn)（見5.6.4）。應(yīng)記錄版本號(hào)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.

 

如果修訂內(nèi)容影響了臨床研究的完整性，則應(yīng)對(duì)修訂前后收集的數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析，以評(píng)估修訂對(duì)性能、有效性或安全性分析的影響。該分析應(yīng)納入臨床研究報(bào)告。

 

7.5.2. Subject identification log受試者識(shí)別代碼

 

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.

 

每個(gè)研究中心應(yīng)保存參與臨床研究的所有受試者的記錄，并指定與其姓名、替代受試者身份或聯(lián)系信息相關(guān)的識(shí)別代碼。

 

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：根據(jù)臨床研究的設(shè)計(jì)，可以在研究中心保存一個(gè)鑒認(rèn)代碼表，以確定所有已被預(yù)先篩查并可能參加臨床研究的人。

 

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.

 

源文件應(yīng)由整個(gè)臨床研究過程中的研究中心團(tuán)隊(duì)創(chuàng)建和維護(hù)。應(yīng)記錄這些源文件的類型和位置。

 

7.6.Additional members of the investigation site team研究中心小組的額外成員

 

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.

 

研究中心小組的新成員可能會(huì)不時(shí)在新中心或現(xiàn)有中心增加。新成員應(yīng)在充分接受臨床研究所要求的培訓(xùn)后才開始任務(wù)，該培訓(xùn)應(yīng)以予記錄。應(yīng)記錄新成員的姓名、首字母縮寫、簽名、職能和職責(zé)授權(quán)。

 

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：除了這些職責(zé)的內(nèi)部現(xiàn)場文件和新成員培訓(xùn)外，研究中心團(tuán)隊(duì)的新成員在開始履行職責(zé)之前可能需要獲得倫理委員會(huì)的批準(zhǔn)。

 

7.7.Subject privacy and confidentiality of data受試者隱私和數(shù)據(jù)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.

 

在整個(gè)臨床研究過程中，各方應(yīng)遵守?cái)?shù)據(jù)的保密性。所有數(shù)據(jù)應(yīng)防止未經(jīng)授權(quán)的訪問。

 

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

 

在報(bào)告和發(fā)布任何數(shù)據(jù)時(shí)，應(yīng)確保每個(gè)受試者的隱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應(yīng)在臨床研究期間和之后確?？梢灾苯釉L問源數(shù)據(jù)，以便用于監(jiān)查、稽查、倫理審查和監(jiān)管機(jī)構(gòu)檢查。根據(jù)需要，主要研究者或研究中心應(yīng)在開始臨床前獲得從受試者、醫(yī)院管理部門和監(jiān)管機(jī)構(gòu)那里獲得直接訪問源文件的許可。

 

7.8.Document and data control文件和數(shù)據(jù)控制

 

7.8.1. Traceability of documents and data文件和數(shù)據(jù)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.

 

所有文件和數(shù)據(jù)的生產(chǎn)和維護(hù)應(yīng)確?？煽啃浴⑼暾?、可控性和可追溯性。與臨床研究相關(guān)的所有文件和后續(xù)版本應(yīng)是可識(shí)別的、可追溯的，并適當(dāng)存儲(chǔ)以提供完整的臨床研究歷程。在某些情況下，應(yīng)保證并記錄翻譯的準(zhǔn)確性。

 

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]).

 

研究者應(yīng)確保在病例報(bào)告表和所有需要報(bào)告給申辦者的數(shù)據(jù)的準(zhǔn)確性、屬性、完整性、可讀性和及時(shí)性。所有保留的原始源文件的副本都應(yīng)經(jīng)過認(rèn)證，并由研究中心小組成員的簽名注明日期，除非是通過經(jīng)驗(yàn)證的流程生成。對(duì)電子源數(shù)據(jù)的獲取、審查和存檔應(yīng)有特殊要求，以確?？煽啃浴①|(zhì)量、完整性和可追溯性(見參考文獻(xiàn) [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.

 

如果治療組的分配采用某種盲法或掩蓋，則應(yīng)在整個(gè)臨床研究過程中予以維護(hù)，包括數(shù)據(jù)輸入和處理。應(yīng)遵循揭盲/設(shè)盲臨床研究的操作流程。

 

7.8.2. Recording of data數(shù)據(jù)記錄

 

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.

 

病例報(bào)告表上報(bào)告的數(shù)據(jù)應(yīng)來自于源文件，并與這些源文件相一致，任何差異應(yīng)以書面形式解釋。臨床研究計(jì)劃應(yīng)規(guī)定哪些數(shù)據(jù)可以直接記錄在病例報(bào)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：在病例報(bào)告表中直接輸入源數(shù)據(jù)可受制于醫(yī)院的具體文件要求。

 

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

 

注2：可直接記錄在病例報(bào)告表中的數(shù)據(jù)也可以注明在監(jiān)查計(jì)劃中。

 

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.

 

病例報(bào)告表應(yīng)由主要研究者或經(jīng)授權(quán)的指定人員簽署并注明日期。對(duì)病例報(bào)告表上報(bào)告中的任何數(shù)據(jù)進(jìn)行變更或更正時(shí)應(yīng)注明日期、姓名縮寫，必要時(shí)應(yīng)予以解釋，且不得掩蓋原始記錄（即應(yīng)保持稽查軌跡）；這適用于紙質(zhì)和電子修改或更正。

 

The sponsor shall:

申辦者應(yīng)：

 

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,

 

指導(dǎo)主要研究者或其授權(quán)指定人員作出正確的變更；申辦者應(yīng)制定標(biāo)準(zhǔn)操作流程以確保病例報(bào)告表中的變更或更正是有文件記錄的，是必要的，是清晰和可追溯的，并由主要研究者或其授權(quán)指定人員認(rèn)可；應(yīng)保存變更和更正的記錄，

 

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

 

如果數(shù)據(jù)在采集過程中進(jìn)行轉(zhuǎn)換，確保原始數(shù)據(jù)和處理后的觀測數(shù)據(jù)可以進(jìn)行比較。

 

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.

 

使用一個(gè)明確的受試者識(shí)別代碼以識(shí)別每個(gè)受試者所報(bào)告的所有數(shù)據(jù)。識(shí)別代碼和每個(gè)受試者之間的關(guān)聯(lián)應(yīng)由主要研究者保留在一個(gè)安全的地方。

 

7.8.3. Electronic clinical data systems臨床電子數(shù)據(jù)系統(tǒng)

 

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.

 

臨床電子數(shù)據(jù)系統(tǒng)的驗(yàn)證是必要的，以評(píng)估數(shù)據(jù)系統(tǒng)的真實(shí)性、準(zhǔn)確性、可靠性，以及從設(shè)計(jì)到系統(tǒng)退役或轉(zhuǎn)移到另一個(gè)新系統(tǒng)的預(yù)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.

 

這些要求適用于3.21中定義的任何電子記錄，包括電子病例報(bào)告表、用于輸入和處理從中心接收的紙質(zhì)病例報(bào)告表數(shù)據(jù)的電子系統(tǒng)以及臨床所需的其他電子系統(tǒng)。

 

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

 

當(dāng)使用電子臨床數(shù)據(jù)庫或臨床電子數(shù)據(jù)系統(tǒng)時(shí)，應(yīng)按約定的流程執(zhí)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,

 

描述系統(tǒng)驗(yàn)證和功能測試、數(shù)據(jù)收集和處理、系統(tǒng)維護(hù)、系統(tǒng)安全措施、變更控制、數(shù)據(jù)備份、恢復(fù)、應(yīng)急計(jì)劃，和退役，

 

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

 

建立和記錄臨床電子數(shù)據(jù)系統(tǒng)接收和處理數(shù)據(jù)的要求，

 

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

 

確認(rèn)并驗(yàn)證臨床電子數(shù)據(jù)系統(tǒng)的要求可以符合一致性要求，

 

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

 

保數(shù)據(jù)的屬性、完整性、可靠性、一致性和數(shù)據(jù)錄入的邏輯性，

 

e) ensure accuracy of reports,

 

確認(rèn)報(bào)告的準(zhǔn)確性，

 

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,

 

確保數(shù)據(jù)變更被記錄下來，并且沒有刪除輸入的數(shù)據(jù)，如維護(hù)稽查軌跡、數(shù)據(jù)軌跡和編輯軌跡，

 

NOTE：National regulations on data protection can require deletion.

 

注：國家數(shù)據(jù)保護(hù)法規(guī)可能需要?jiǎng)h除。

 

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

 

維護(hù)一個(gè)安全系統(tǒng)，防止在內(nèi)部和外部未經(jīng)授權(quán)地訪問數(shù)據(jù)，

 

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,

 

維護(hù)一份可以訪問電子數(shù)據(jù)系統(tǒng)的個(gè)人名單，以及訪問日期、授予每個(gè)用戶的權(quán)限和取消訪問權(quán)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,

 

通過主要研究者或授權(quán)指定人員的簽名，確保報(bào)告給申辦者的數(shù)據(jù)的準(zhǔn)確性和完整性，

 

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

 

維護(hù)數(shù)據(jù)足夠的備份、存檔和可檢索性，

 

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

 

培訓(xùn)用戶了解如何使用該系統(tǒng)，以及

 

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

 

如果設(shè)盲應(yīng)以予保持（例如在數(shù)據(jù)輸入和處理過程中保持盲態(tài)）。

 

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.

 

研究器械的使用應(yīng)受到控制，研究器械應(yīng)僅在臨床研究并根據(jù)臨床研究計(jì)劃使用。

 

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:

 

申辦者應(yīng)保存記錄，以記錄所有研究器械的從研究器械運(yùn)輸?shù)窖芯恐行牡交厥栈蛱幹玫拇娣盼恢?。申辦者應(yīng)有適當(dāng)?shù)恼f明，并提供包裝材料，用于安全回收或處置研究器械，包括潛在危險(xiǎn)的器械。主要研究者或授權(quán)人員應(yīng)當(dāng)記錄以下內(nèi)容：

 

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

 

接收、使用、歸還或處置這些器械的人員姓名；

 

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

 

每個(gè)試驗(yàn)器械的接收日期、編碼和數(shù)量（批號(hào)/序列號(hào)或唯一編碼）；

 

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;

 

受試者編碼；

 

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

 

受試者歸還/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;

 

歸還未使用、過期或出現(xiàn)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.

 

根據(jù)申辦者的說明處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.

 

整個(gè)器械管理過程應(yīng)建立標(biāo)準(zhǔn)操作流程。

 

7.10.Accounting for subjects受試者審查

 

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.

 

所有參與臨床研究的受試者（包括退出臨床研究或失訪的受試者）應(yīng)進(jìn)行審查和記錄。

 

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.

 

如果受試者退出臨床研究，應(yīng)記錄其原因。研究者可以使用現(xiàn)有的數(shù)據(jù)，并請求受試者許可收集其有關(guān)他/她的癥狀/健康的隨訪數(shù)據(jù)，包括相關(guān)器械的臨床性能、有效性或安全性的信息。如獲得許可，應(yīng)將相關(guān)資料納入臨床研究報(bào)告。

 

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

 

注：從退出的受試者中收集的隨訪數(shù)據(jù)受制于國家法規(guī)。

 

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.

 

可以對(duì)臨床研究進(jìn)行稽查，以評(píng)估對(duì)臨床研究計(jì)劃、操作流程、本文件和適用的法規(guī)要求的符合性(見附件J)。這些稽查可能涵蓋所有相關(guān)方、系統(tǒng)、流程和設(shè)施，并獨(dú)立于質(zhì)量控制或常規(guī)監(jiān)查。

 

An audit can be used

 

稽查可以用于以下情況：

 

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

 

作為申辦者質(zhì)量保證的一個(gè)常規(guī)部分，

 

b) to assess the effectiveness of the monitoring activity,

 

評(píng)估監(jiān)查活動(dòng)的有效性，

 

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

 

每當(dāng)有嚴(yán)重或反復(fù)的臨床研究計(jì)劃偏離或懷疑欺詐時(shí)，

 

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

 

使研究中心進(jìn)入“檢查準(zhǔn)備狀態(tài)”(即，研究中心為潛在的監(jiān)管機(jī)構(gòu)檢查做準(zhǔn)備查），

 

e) when requested or suggested by a regulatory authority.

 

當(dāng)被監(jiān)管機(jī)構(gòu)要求或建議時(shí)。

 

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

 

稽查員應(yīng)進(jìn)行相應(yīng)的培訓(xùn)并具有稽查經(jīng)驗(yàn)，且應(yīng)獨(dú)立于臨床研究。

 

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.

 

臨床研究體系和流程的稽查應(yīng)按照操作流程或特定計(jì)劃確認(rèn)稽查內(nèi)容、稽查方式、稽查頻率、稽查報(bào)告的形式和內(nèi)容，以及稽查證明書。

 

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).

 

臨床研究稽查的稽查計(jì)劃或流程應(yīng)以臨床研究的重要性、臨床研究對(duì)象的數(shù)量、臨床研究的類型和復(fù)雜性、對(duì)受試者的風(fēng)險(xiǎn)水平以及任何已確定的風(fēng)險(xiǎn)為指導(dǎo)。

 

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

 

稽查結(jié)果應(yīng)被記錄下來，并傳達(dá)給相關(guān)各方。如適用，應(yīng)在申辦者文件中保存稽查證明書。

 

8.Suspension, termination, and close-out of the clinical investigation暫停、終止和結(jié)束臨床研究

 

8.1.Completion of the clinical investigation完成臨床試驗(yàn)

 

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.

 

臨床研究的完成應(yīng)視為末例受試者的末次隨訪與臨床研究隨訪完成同時(shí)發(fā)生，無論臨床研究是否按照預(yù)先制定的臨床研究計(jì)劃結(jié)束或提前終止，除非臨床研究計(jì)劃為試驗(yàn)完成規(guī)定了另一個(gè)時(shí)間點(diǎn)。

 

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

 

注：臨床研究的完成也可以稱為臨床研究的結(jié)束。

 

8.2.Suspension or premature termination of the clinical investigation暫停或提前終止臨床研究

 

8.2.1. Procedure for suspension or premature termination暫?；蛱崆敖K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.

 

申辦者可因重大的和有記錄的原因，如在數(shù)據(jù)監(jiān)查委員會(huì)推薦的情況下，暫停或提前終止在個(gè)別研究中心或整個(gè)臨床研究。

 

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、倫理委員會(huì)或監(jiān)管機(jī)構(gòu)可暫?；蛱崆敖K止他們所負(fù)責(zé)的研究中心的臨床研究。

 

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).

 

如果在臨床研究過程中懷疑存在不可接受的風(fēng)險(xiǎn)，包括在臨床研究中出現(xiàn)對(duì)受試者有嚴(yán)重健康威脅，或在倫理委員會(huì)或監(jiān)管機(jī)構(gòu)的指示下，申辦者應(yīng)暫停臨床研究以評(píng)估風(fēng)險(xiǎn)。如果確認(rèn)存在無法控制的不可接受的風(fēng)險(xiǎn)，申辦者應(yīng)終止臨床研究（見圖7.4.4和圖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.

 

如果監(jiān)查或稽查中發(fā)現(xiàn)部分研究者出現(xiàn)嚴(yán)重或反復(fù)的偏離時(shí)，申辦者應(yīng)考慮終止或暫停某家研究中心或研究者參與臨床研究。

 

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.

 

如發(fā)生暫?；蛱崆敖K止，終止方應(yīng)以書面形式證明其決定的合理性，并立即通知與其直接溝通的其他相關(guān)方。

 

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

 

注1：通常的溝通線路是申辦者<->主要研究者或申辦者<->倫理委員會(huì)和申辦者<->監(jiān)管機(jī)構(gòu)

 

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

 

主要研究者和申辦者應(yīng)隨時(shí)告知從倫理委員會(huì)或監(jiān)管機(jī)構(gòu)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.

 

如果申辦者出于任何原因暫停或提前終止在個(gè)別研究中心的研究，申辦者應(yīng)適當(dāng)?shù)赝ㄖ?fù)責(zé)的監(jiān)管機(jī)構(gòu)，并確保由主要研究者或申辦者通知倫理委員會(huì)。如果暫停或提前終止為了安全（見7.4.4和圖H.1），申辦者應(yīng)通知所有其他主要研究者。

 

If suspension or premature termination occurs,

 

如果暫?；蛱崆敖K止發(fā)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

 

申辦者應(yīng)繼續(xù)負(fù)責(zé)提供資源，以履行對(duì)參與臨床研究的受試者的隨訪義務(wù)，以及

 

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

 

主要研究者或授權(quán)指定人員應(yīng)立即通知在其研究中心招募的受試者，如果合適。

 

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

 

注2：這種溝通的方法和時(shí)間取決于情況、預(yù)知的風(fēng)險(xiǎn)和國家法規(guī)。

 

All activities listed in 8.3 shall also be conducted.

 

8.3中列出的所有活動(dòng)也應(yīng)進(jìn)行。

 

8.2.2. Procedure for resuming the clinical investigation after temporary suspension恢復(fù)暫停后的臨床研究程序

 

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.

 

當(dāng)申辦者對(duì)暫停的原因進(jìn)行分析，實(shí)施必要的糾正措施并決定解除暫停時(shí)，申辦者應(yīng)通知主要研究者、倫理委員會(huì)。在必要的情況下，向監(jiān)管機(jī)構(gòu)應(yīng)提供理由并向其提供支持該決定的相關(guān)數(shù)據(jù)。

 

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

 

注意：通常的溝通線路是申辦者<->主要研究者或申辦者<->倫理委員會(huì)和申辦者<->監(jiān)管機(jī)構(gòu)

 

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

 

在臨床研究恢復(fù)前，應(yīng)獲得倫理委員會(huì)，必要時(shí)還應(yīng)獲得監(jiān)管機(jī)構(gòu)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.

 

如果受試者已被告知暫停，主要研究者或授權(quán)指定人員應(yīng)告知他們重新開始的原因。

 

8.3.Routine close-out常規(guī)關(guān)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.

 

應(yīng)進(jìn)行常規(guī)的關(guān)中心動(dòng)作，以確保主要研究者的記錄完整、所有申辦者所需的文件都?xì)w檔、剩余的臨床研究物資得到處理、先前確認(rèn)的問題得到解決，并通知各相關(guān)方。

 

a) Completing the records includes ensuring that

 

完成記錄以確保

 

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

 

所有必要的文件都是完整且為最新，

 

2) all CRFs are completed,

 

所有的病例報(bào)告表都完成，

 

3) all outstanding queries are resolved,

 

所有未解決的質(zhì)疑都已解決，

 

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

 

所有持續(xù)的不良事件的當(dāng)前狀態(tài)都已經(jīng)記錄，

 

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

 

已經(jīng)為存檔和記錄保存做出安排，以及

 

6) documenting disposition of any:

 

記錄任何物資處置情況：

 

i) investigational devices;

 

研究器械；

 

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

 

剩余樣本（例如，血液或組織）；

 

iii) other clinical investigation materials.

 

其他臨床研究物資。

 

b) Notification includes:

 

通知包括：

 

1) notification to EC;

 

通知倫理委員會(huì)；

 

2) notification to regulatory authorities, if required;

 

通知監(jiān)管機(jī)構(gòu)，如必要；

 

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

 

注：某些國家法規(guī)也可能要求在特定時(shí)間內(nèi)完成。

 

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

 

在公開訪問的數(shù)據(jù)庫中通報(bào)臨床研究完成(見 5.4).

 

8.4.Clinical investigation report臨床研究報(bào)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.

 

臨床研究結(jié)束后，即使臨床研究提前終止，也應(yīng)完成臨床研究報(bào)告。臨床研究報(bào)告應(yīng)包括附件D中規(guī)定的內(nèi)容。

 

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

 

注1：國家法規(guī)可能會(huì)對(duì)臨床研究報(bào)告完成和報(bào)告內(nèi)容提出要求。

 

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

 

臨床研究報(bào)告應(yīng)以書面形式完成；

 

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.

 

臨床研究報(bào)告應(yīng)包括器械的識(shí)別、臨床研究的方法和設(shè)計(jì)的描述、對(duì)方案的任何偏離、采用各類統(tǒng)計(jì)方法的數(shù)據(jù)分析結(jié)果，并對(duì)結(jié)果與臨床研究目標(biāo)進(jìn)行了批判性評(píng)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.

 

臨床研究報(bào)告中的結(jié)果應(yīng)以可重復(fù)和可追溯的方式來自于病例報(bào)告表的數(shù)據(jù)和其他必要的數(shù)據(jù)采集方法。應(yīng)保存證明這一點(diǎn)的記錄。

 

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.

 

臨床研究報(bào)告應(yīng)考慮每個(gè)研究中心和所有受試者的數(shù)據(jù)。無論是從臨床研究報(bào)告還是公布的結(jié)果中，都不能識(shí)別任何受試者。

 

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.

 

臨床研究報(bào)告應(yīng)在適用時(shí)提供給協(xié)調(diào)研究者和所有主要研究者進(jìn)行審查和評(píng)論。申辦者應(yīng)進(jìn)行記錄，確認(rèn)已提供臨床研究報(bào)告以供審查。如果審稿人不同意全部或部分臨床研究報(bào)告，應(yīng)記錄其意見并傳達(dá)給其他主要研究者。

 

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.

 

應(yīng)要求申辦者和協(xié)調(diào)研究者提供其簽名，表明其對(duì)臨床研究報(bào)告內(nèi)容的同意。如果沒有指定協(xié)調(diào)研究者，應(yīng)獲得主要研究者的簽字。

 

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

 

臨床研究報(bào)告應(yīng)提供給倫理委員會(huì)和監(jiān)管機(jī)構(gòu)。

 

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.

 

臨床研究的結(jié)果應(yīng)錄入臨床研究所登記的公開數(shù)據(jù)庫(見 5.4)并發(fā)表了一些文章，無論是正向的、不確定的、還是反向的，以幫助指導(dǎo)未來的研究、器械開發(fā)和醫(yī)學(xué)治療。

 

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

 

注2：關(guān)于臨床研究報(bào)告內(nèi)容的進(jìn)一步指導(dǎo)見附錄D。

 

8.5.Risk assessment and conclusions風(fēng)險(xiǎn)評(píng)估和結(jié)論

 

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.

 

在臨床研究完成后(見D.8)應(yīng)對(duì)風(fēng)險(xiǎn)信息進(jìn)行正式審查，并納入風(fēng)險(xiǎn)分析和臨床評(píng)價(jià)并更新兩份文件中的受益-風(fēng)險(xiǎn)結(jié)論。

 

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.

 

申辦者和主要研究者應(yīng)保存臨床研究文件。他們應(yīng)采取措施，防止這些文件的意外或過早銷毀。主要研究者或申辦者可將研究中心或申辦者機(jī)構(gòu)內(nèi)的文件保管轉(zhuǎn)移給另一人/機(jī)構(gòu)。

 

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

 

注：申辦者需保存的必要臨床研究文件清單和研究中心文件見附件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.

 

臨床研究文件，包括但不限于研究方案、研究者手冊、病例報(bào)告表和臨床研究報(bào)告，應(yīng)整合至制造商質(zhì)量管理體系下的醫(yī)療器械技術(shù)文件。對(duì)于申辦者-研究者發(fā)起的臨床研究，應(yīng)盡可能地參考上述原則。

 

9.Responsibilities of the sponsor申辦者的職責(zé)

 

9.1.Clinical quality management臨床質(zhì)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

 

質(zhì)量管理原則應(yīng)運(yùn)用于臨床研究過程，以確保臨床研究的設(shè)計(jì)、實(shí)施、監(jiān)查，以及數(shù)據(jù)的生成、文件化、記錄、評(píng)價(jià)、報(bào)告依從于本文件、研究方案、任何后續(xù)修訂和任何其他適用標(biāo)準(zhǔn)，同時(shí)符合法規(guī)要求。申辦者應(yīng)該

 

a) implement and maintain written clinical quality procedures,

 

實(shí)施和維護(hù)已經(jīng)制定的臨床質(zhì)量流程，

 

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

 

維護(hù)記錄，以記錄參與臨床研究的各方的合規(guī)性，

 

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

 

確保符合7.11的稽查要求，如果適用，以及，

 

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

 

證明并記錄本文件要求以外的重大情況（豁免示例見附件I）。

 

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

 

臨床質(zhì)量流程可以整合到申辦者的整個(gè)質(zhì)量體系的適用部分。

 

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

 

注：有關(guān)更多信息，請參見ISO 13485或同等的法規(guī)要求。

 

9.2.Clinical investigation planning and conduct臨床研究的計(jì)劃和實(shí)施

 

9.2.1. Selection and training of clinical personnel臨床工作人員的選擇和培訓(xùn)

 

Prior to commencement of the clinical investigation, the sponsor shall

 

在臨床研究開始前，申辦者應(yīng)負(fù)責(zé)

 

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,

 

在一個(gè)或多個(gè)書面協(xié)議中定義、確認(rèn)和分配與臨床研究相關(guān)人員的所有角色和責(zé)任，如6.9定義，

 

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),

 

如果申辦者不是擬進(jìn)行臨床研究所在國的居民，則需要選擇一名當(dāng)?shù)卮砣艘月男猩贽k者在該國（這些國家）的全部責(zé)任。

 

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

 

注：國家或地區(qū)法規(guī)可能有涉及代理人選擇的要求。

 

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

 

選擇適當(dāng)?shù)暮细竦闹饕芯空撸缰?.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，進(jìn)行多中心研究時(shí)選擇一個(gè)協(xié)調(diào)研究者，

 

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

 

對(duì)主要研究者和研究者的利益沖突進(jìn)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,

 

確保研究中心團(tuán)隊(duì)成員及其指定授權(quán)人員在正式記錄中得到確認(rèn)，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個(gè)獨(dú)立于研究中心的監(jiān)查員，或以其他方式承擔(dān)監(jiān)查員的職責(zé)，

 

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

 

確保所有相關(guān)方的培訓(xùn)、經(jīng)驗(yàn)、科學(xué)或臨床知識(shí)得以記錄和驗(yàn)證，以便足以實(shí)施臨床研究，包括在以下方面的培訓(xùn)：

 

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

 

研究器械以及相關(guān)對(duì)照產(chǎn)品的使用，

 

2) device accountability procedures (see 7.9),

 

研究器械管理，

 

3) IB,

 

研究者手冊，

 

4) CIP,

 

臨床研究計(jì)劃，

 

5) CRFs,

 

病例報(bào)告表，

 

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

 

提供給受試者的書面知情同意書、流程以及其他書面信息，以及

 

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

 

申辦者的標(biāo)準(zhǔn)操作流程、本文件和適用的監(jiān)管法規(guī)所需的東西；

 

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,

 

確保在多中心研究中，所有研究者和所有其他相關(guān)方都得到了關(guān)于統(tǒng)一對(duì)臨床和實(shí)驗(yàn)室發(fā)現(xiàn)的評(píng)價(jià)和記錄的指導(dǎo)，

 

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,

 

確保在研究方案和知情同意書中描述了任何涉及受試者和申辦者代表潛在接觸的臨床研究相關(guān)活動(dòng)，并且這些活動(dòng)的發(fā)生方式不會(huì)使數(shù)據(jù)完整性產(chǎn)生偏離，

 

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：在實(shí)施臨床研究時(shí)提供技術(shù)專長的監(jiān)查員、現(xiàn)場工程師或產(chǎn)品專家等都是申辦者的代表。

 

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

 

如必要，考慮組建數(shù)據(jù)監(jiān)查委員會(huì)。

 

9.2.2. Preparation of documents and materials文件和物資準(zhǔn)備

 

Prior to commencement of the clinical investigation, the sponsor shall

 

在臨床研究開始之前，申辦者應(yīng)該

 

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條、第6條和第7條的規(guī)定準(zhǔn)備文件，并確保相關(guān)人員簽字批準(zhǔn)；如果需要，應(yīng)向所有相關(guān)方提供副本，必要時(shí)獲得注明日期的簽名，

 

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

 

確保翻譯的準(zhǔn)確性，當(dāng)相關(guān)時(shí)，

 

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,

 

確保及時(shí)為臨床研究提供7.9所述的研究器械；在達(dá)到開展臨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,

 

建立一個(gè)程序確保器械管理，以使得能夠立即識(shí)別，并在必要時(shí)召回臨床研究使用的器械，

 

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

 

在發(fā)生臨床研究相關(guān)傷害的情況下，提供涵蓋受試者治療費(fèi)用的保險(xiǎn)，如必要，

 

NOTE：Certain national or local regulations can apply.

 

注：參考特定國家或地區(qū)的法規(guī)。

 

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

 

記錄主要研究者或研究中心與申辦者之間的任何財(cái)務(wù)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,

 

向相關(guān)監(jiān)管機(jī)構(gòu)提交在特定國家開始臨床研究所需的任何申請，以供審查、批準(zhǔn)或許可，

 

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,

 

確保獲得倫理委員會(huì)的批準(zhǔn)/贊成意見并形成文件，并作出適當(dāng)?shù)臈l款以滿足倫理委員會(huì)所規(guī)定的任何條件，

 

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,

 

確保倫理委員會(huì)或監(jiān)管機(jī)構(gòu)要求的任何修改均由主要研究者完成并記錄，并獲得倫理委員會(huì)或監(jiān)管機(jī)構(gòu)的批準(zhǔn)/贊成意見，

 

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

 

在招募第一個(gè)受試者之前，在一個(gè)公共數(shù)據(jù)庫中登記臨床研究的信息(見5.4)。

 

9.2.3. Conduct of clinical investigation臨床研究實(shí)施

 

The sponsor shall be responsible for

 

申辦者應(yīng)負(fù)責(zé)：

 

a) accountability of investigational devices throughout the clinical investigation,

 

在整個(gè)臨床研究中對(duì)研究器械進(jìn)行管理，

 

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

 

記錄與臨床研究相關(guān)各方的溝通內(nèi)容，包括倫理委員會(huì)和監(jiān)管機(jī)構(gòu)，

 

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,

 

通過確定監(jiān)查的范圍和性質(zhì)確保臨床研究得到適當(dāng)?shù)谋O(jiān)查，包括基于臨床研究目的、設(shè)計(jì)、復(fù)雜性、規(guī)模、關(guān)鍵數(shù)據(jù)點(diǎn)和終點(diǎn)等因素的源數(shù)據(jù)核查策略，

 

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

 

確保執(zhí)行風(fēng)險(xiǎn)管理活動(dòng)并以予記錄（參見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),

 

審查監(jiān)查報(bào)告，并跟進(jìn)監(jiān)查報(bào)告中所需的任何行動(dòng)（見9.2.4.7），

 

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

 

迅速采取行動(dòng)，確保符合所有臨床研究的要求，

 

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,

 

如果不合規(guī)嚴(yán)重影響或可能嚴(yán)重影響受試者保護(hù)或臨床研究結(jié)果的可靠性，需要進(jìn)行根本原因分析并記錄以實(shí)施適當(dāng)?shù)募m正和預(yù)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.

 

在確認(rèn)數(shù)據(jù)完整性后，當(dāng)有要求時(shí)，應(yīng)向所有倫理委員會(huì)和監(jiān)管機(jī)構(gòu)提交進(jìn)度報(bào)告，包括安全總結(jié)和偏離。

 

9.2.4. Monitoring監(jiān)查

 

9.2.4.1. General概述

 

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

 

應(yīng)按照監(jiān)查計(jì)劃進(jìn)行監(jiān)查（見6.7）。

 

The purpose of clinical investigation monitoring is to verify that

 

臨床研究監(jiān)查的目的是為了確認(rèn)

 

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

 

對(duì)人類受試者的權(quán)利、安全和福祉的保護(hù)，

 

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

 

報(bào)告的數(shù)據(jù)準(zhǔn)確、完整，并可從源文件中得到確認(rèn)，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.

 

臨床研究的進(jìn)行符合批準(zhǔn)的研究方案、后續(xù)修訂、本文件、適用的監(jiān)管要求、適用的倫理委員會(huì)要求。

 

9.2.4.2. Qualifications of the monitor監(jiān)查員的資質(zhì)

 

Monitors shall be

 

監(jiān)查員應(yīng)

 

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

 

通過培訓(xùn)，以及有科學(xué)和臨床相關(guān)知識(shí)的經(jīng)驗(yàn)以獲得本文件所涉及的資格，

 

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關(guān)要求、研究方案、知情同意過程（見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.

 

培訓(xùn)內(nèi)容包括與監(jiān)查活動(dòng)相關(guān)的申辦者臨床質(zhì)量管理流程，以及監(jiān)查特定臨床研究中的任何特殊流程。

 

Training shall be documented in the sponsor's files.

 

培訓(xùn)應(yīng)記錄在申辦者的文件中。

 

9.2.4.3. Assessment of the investigation site對(duì)研究中心評(píng)估

 

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

 

監(jiān)查員應(yīng)評(píng)估每個(gè)研究中心，以核實(shí)主要研究者是否有

 

a) adequate qualifications,

 

足夠的資質(zhì)，

 

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

 

充足的資源，包括設(shè)施、實(shí)驗(yàn)室、設(shè)備和一個(gè)合格的研究團(tuán)隊(duì)，

 

c) access to an adequate number of subjects.

 

評(píng)估是否有足夠的受試者數(shù)量。

 

9.2.4.4. Initiation of the investigation site研究中心啟動(dòng)

 

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

 

監(jiān)查人員應(yīng)根據(jù)監(jiān)查計(jì)劃啟動(dòng)每個(gè)研究中心，以確保主要研究員和研究中心團(tuán)隊(duì)

 

a) have received and understood the requirements and contents of

 

已經(jīng)接收并了解以下要求和內(nèi)容

 

1) the CIP,

 

臨床研究計(jì)劃

 

2) the IB,

 

研究者手冊

 

3) the informed consent form,

 

知情同意書

 

4) the CRFs,

 

病例報(bào)告表

 

5) the instructions for use,

 

使用說明

 

6) any written clinical investigation agreements, as appropriate,

 

任何書面的臨床研究協(xié)議，如必要，

 

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

 

能夠獲得足夠數(shù)量的研究器械，

 

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

 

接受過研究器械使用方面的培訓(xùn)，

 

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

 

熟悉主要研究者的職責(zé)，如第10章節(jié)所述。

 

9.2.4.5. Routine monitoring visits常規(guī)監(jiān)查訪視

 

The monitor shall perform routine monitoring activities to verify that

 

監(jiān)查員應(yīng)執(zhí)行常規(guī)監(jiān)查活動(dòng)以核實(shí)以下情況：

 

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、任何后續(xù)修訂、本文件和監(jiān)管要求；偏離應(yīng)與主要研究者或授權(quán)指定人員討論，并形成文件并報(bào)告給申辦者，

 

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)所述的授權(quán)成員參與臨床研究，

 

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，必要時(shí)也包括對(duì)照器械，根據(jù)研究方案、研究者手冊或使用說明的要求使用，當(dāng)需要對(duì)器械、其使用方法或研究方案進(jìn)行修改時(shí)，這些將通報(bào)給申辦者，

 

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

 

研究中心資源，包括實(shí)驗(yàn)室、設(shè)備和研究團(tuán)隊(duì)，在整個(gè)臨床研究過程中保證充足，

 

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

 

主要研究者能夠持續(xù)獲得足夠數(shù)量的受試者和研究器械，

 

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,

 

在進(jìn)行任何臨床研究相關(guān)流程之前，已從每個(gè)受試者或其法定代表人處獲得簽署名字和注明日期的知情同意書，

 

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，包括文件類型和位置，以及其他臨床研究記錄應(yīng)準(zhǔn)確、完整、及時(shí)、妥善地存儲(chǔ)和維護(hù)，

 

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,

 

病例報(bào)告表和質(zhì)疑表應(yīng)及時(shí)記錄并完成，與源文件一致，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,

 

對(duì)病例報(bào)告表進(jìn)行適當(dāng)?shù)母⑻砑踊騽h除應(yīng)注明日期，必要時(shí)應(yīng)解釋原因，并由主要研究者或其授權(quán)指定人簽字；監(jiān)查員不得對(duì)病例報(bào)告表進(jìn)行更正、添加或刪除，

 

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,

 

受試者未進(jìn)行的隨訪、未進(jìn)行測試或未進(jìn)行檢查，以及受試者退出（如果可能注明原因）適當(dāng)?shù)貓?bào)告在病例報(bào)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經(jīng)報(bào)告給申辦者，所有可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的嚴(yán)重不良事件和器械缺陷都已經(jīng)報(bào)告給申辦者，且沒有不合理的延遲，

 

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，有可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的嚴(yán)重不良事件和器械缺陷都已經(jīng)報(bào)告給倫理委員會(huì)和監(jiān)管機(jī)構(gòu)，

 

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

 

偏離（見5.6.4b)已經(jīng)報(bào)告給倫理委員會(huì)，也同時(shí)報(bào)告給了監(jiān)管機(jī)構(gòu)，

 

NOTE：National regulations can also apply.

 

注：依據(jù)不同國家法規(guī)執(zhí)行。

 

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

 

研究器械的儲(chǔ)存和管理是正確的，可追溯過程并記錄在研究者的文件中，

 

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,

 

所有所需的報(bào)告、通知、申請、遞交和通信都保存在研究者文件夾中，并且準(zhǔn)確、完整、及時(shí)、清晰、注明日期以區(qū)別于不同的臨床研究，

 

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，與臨床研究評(píng)估相關(guān)設(shè)備的維護(hù)和校準(zhǔn)被適當(dāng)?shù)貓?zhí)行并記錄，

 

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

 

如需要，研究者文件夾中包含了當(dāng)前的實(shí)驗(yàn)室正常值，實(shí)驗(yàn)室證書、認(rèn)證或其他驗(yàn)證，

 

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

 

受試者退出已記錄在案；監(jiān)查員應(yīng)與主要研究者或其授權(quán)指定人員討論此情況，

 

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,

 

受試者不符合知情同意書中注明的要求已被記錄下來；監(jiān)查員應(yīng)與主要研究者或其授權(quán)指定人員討論此情況，

 

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

 

主要研究者和研究團(tuán)隊(duì)已經(jīng)被告知并了解與臨床研究相關(guān)的所有最新文件，

 

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

 

如需要，任何糾正和預(yù)防措施都已得到有效的實(shí)施。

 

9.2.4.6. Close-out activities關(guān)中心活動(dòng)

 

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

 

監(jiān)查員應(yīng)執(zhí)行第8章節(jié)中所述的關(guān)中心活動(dòng)。

 

9.2.4.7. Monitoring reports監(jiān)查報(bào)告

 

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

 

監(jiān)查活動(dòng)的結(jié)果應(yīng)充分詳細(xì)記錄，以驗(yàn)證對(duì)監(jiān)查計(jì)劃的依從性（見6.7）。

 

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

 

所有監(jiān)查活動(dòng)應(yīng)記錄并報(bào)告給申辦者[參見9.2.3 c)]并應(yīng)包括

 

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

 

日期、研究中心編號(hào)、監(jiān)查員姓名以及主要研究者或其他聯(lián)系人員的姓名，

 

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.

 

監(jiān)查員審查內(nèi)容的摘要，以及他/她對(duì)之前工作內(nèi)容的完成情況、重大發(fā)現(xiàn)、事實(shí)、偏離、結(jié)論，以及為確保合規(guī)而建議采取的行動(dòng)。

 

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

 

監(jiān)查報(bào)告或重要發(fā)現(xiàn)的摘要的副本應(yīng)以書面形式與主要研究者共享。

 

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

 

注：上述要求也可適用于臨床研究相關(guān)的交流，這具體取決于申辦者流程或國家法規(guī)，

 

9.2.5. Safety evaluation and reporting安全評(píng)估和報(bào)告

 

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

 

申辦者負(fù)責(zé)不良事件的分類和對(duì)臨床研究進(jìn)行安全性評(píng)估，并應(yīng)

 

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,

 

審查研究者對(duì)所有不良事件的評(píng)估和決策，并以書面形式確定并記錄其嚴(yán)重性，以及與研究器械和研究方案流程的相關(guān)性；如果申辦者和主要研究者之間存在如下述c）、d）和e）所述的分歧時(shí)，申辦者應(yīng)向有關(guān)各方傳達(dá)兩種意見，

 

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：不良事件的分類和安全性評(píng)估可由一個(gè)獨(dú)立的臨床事件委員會(huì)(CEC)進(jìn)行，以減輕潛在的偏倚和利益沖突。

 

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,

 

審查所有器械缺陷和決策，確定并書面記錄它們是否可能導(dǎo)致嚴(yán)重的器械不良反應(yīng)；如果申辦者和主要研究者之間存在如下述c）、d）和e）所述的分歧時(shí)，申辦者應(yīng)向有關(guān)各方傳達(dá)兩種意見，

 

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,

 

如果研究方案或倫理委員會(huì)要求，主要研究者應(yīng)向倫理委員會(huì)報(bào)告或正在報(bào)告所有可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的嚴(yán)重不良事件和器械缺陷，

 

NOTE 2 Certain national regulations can also apply.

 

注2：某些國家法規(guī)也可以適用。

 

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，應(yīng)在規(guī)定的時(shí)間段內(nèi)，向監(jiān)管機(jī)構(gòu)報(bào)告所有可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的嚴(yán)重不良事件和器械缺陷，包括嚴(yán)重的健康威脅的情況，

 

NOTE 3 Certain national regulations can also apply.

 

注3：某些國家法規(guī)也可以適用。

 

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

 

如果已經(jīng)建立標(biāo)準(zhǔn)操作流程，應(yīng)向數(shù)據(jù)監(jiān)查委員會(huì)報(bào)告所有相關(guān)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),

 

在進(jìn)行多中心臨床研究時(shí)，以書面形式將所有研究中心已報(bào)告給申辦者的所有嚴(yán)重不良事件通知給所有主要研究者，并確保這些事件已經(jīng)報(bào)告給所在的倫理委員會(huì)（如果研究方案或倫理委員會(huì)有要求，以更嚴(yán)格的為準(zhǔn)）；該信息應(yīng)根據(jù)在風(fēng)險(xiǎn)評(píng)估（分析和評(píng)估）中定義的預(yù)知風(fēng)險(xiǎn)，在規(guī)定的時(shí)間內(nèi)發(fā)送給所有主要研究者，

 

NOTE 4：Certain national regulations can also apply.

 

注4：某些國家法規(guī)也可以適用。

 

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

 

確認(rèn)倫理委員會(huì)和監(jiān)管機(jī)構(gòu)被告知與臨床研究相關(guān)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.

 

如果嚴(yán)重不良事件和器械缺陷可能導(dǎo)致嚴(yán)重的器械不良反應(yīng)，確認(rèn)是否需要更新風(fēng)險(xiǎn)分析并評(píng)估是否采取糾正或預(yù)防措施

 

9.2.6. Clinical investigation close-out臨床研究關(guān)閉

 

The sponsor shall

 

申辦者應(yīng)

 

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

 

確保所有臨床研究收尾活動(dòng)按照第8章節(jié)的規(guī)定正確進(jìn)行，

 

b) perform a statistical analysis of the data,

 

并對(duì)其進(jìn)行數(shù)據(jù)統(tǒng)計(jì)分析，

 

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

 

制作臨床研究報(bào)告并提交審查，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,

 

確保臨床研究報(bào)告，無論是一個(gè)已完成或提前終止的臨床研究，已經(jīng)提供給倫理委員會(huì)、參考的研究者以及監(jiān)管機(jī)構(gòu)，

 

NOTE：National regulations can also apply.

 

注：國家法規(guī)也可以適用。

 

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

 

如果適用，將臨床研究結(jié)果更新至公開訪問的數(shù)據(jù)庫（參見5.4）。

 

9.3.Outsourcing of duties and functions職責(zé)和職能的外包

 

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.

 

申辦者可將部分或所有與臨床研究相關(guān)的職責(zé)和職能，包括監(jiān)查，移交給外部組織(如，CRO或個(gè)人承包商)，但對(duì)臨床研究的質(zhì)量和完整性申辦者應(yīng)承擔(dān)最終責(zé)任。申辦者應(yīng)確保對(duì)任何與臨床研究相關(guān)的職責(zé)和職能進(jìn)行監(jiān)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.

 

將職責(zé)或職能外包給外部組織時(shí)，包括申辦者自己管理CRO業(yè)務(wù)的分包商，應(yīng)由申辦者按照供應(yīng)商質(zhì)控標(biāo)準(zhǔn)操作流程進(jìn)行處理。申辦者應(yīng)以書面形式確定由外部組織承擔(dān)的任何與臨床研究相關(guān)的職責(zé)或職能，并保留沒有特別轉(zhuǎn)移給外部組織，也沒有由外部組織承擔(dān)的任何與臨床研究相關(guān)的職責(zé)和職能。應(yīng)保存職責(zé)和職能轉(zhuǎn)移的記錄。

 

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

 

申辦者應(yīng)負(fù)責(zé)驗(yàn)證外部組織是否存在并遵守標(biāo)準(zhǔn)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.

 

本文件中適用于申辦者的所有要求，也應(yīng)適用于外部組織，該組織承擔(dān)與申辦者一樣的臨床研究相關(guān)職責(zé)和職能。

 

9.4.Communication with regulatory authorities與監(jiān)管機(jī)構(gòu)溝通

 

The sponsor shall, if required,

 

如需要，申辦者應(yīng)，

 

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

 

被通知或獲得臨床研究所在國監(jiān)管機(jī)構(gòu)的批準(zhǔn)/贊同，

 

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,

 

在執(zhí)行相關(guān)相關(guān)修訂之前，監(jiān)管機(jī)構(gòu)已經(jīng)對(duì)修改文件進(jìn)行過審閱，并被通知或獲得臨床研究所在國監(jiān)管機(jī)構(gòu)的批準(zhǔn)/贊同，

 

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

 

報(bào)告臨床研究的進(jìn)展和現(xiàn)狀，

 

d) perform safety reporting as specified in 9.2.5,

 

按照9.2.5中的規(guī)定執(zhí)行安全報(bào)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.

 

報(bào)告因受試者安全性或研究器械性能從研究中心撤回研究器械的事件。

 

10.Responsibilities of the principal investigator主要研究者的職責(zé)

 

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.

 

主要研究者的職責(zé)是實(shí)施并對(duì)臨床研究進(jìn)行日常監(jiān)督管理，以確保數(shù)據(jù)的完整性和參與臨床研究的受試者的權(quán)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.

 

主要研究者負(fù)責(zé)確認(rèn)研究中心團(tuán)隊(duì)的資格并使其得到充分培訓(xùn)，同時(shí)持續(xù)對(duì)其活動(dòng)進(jìn)行監(jiān)督。主要研究者可以將任務(wù)委托給研究中心團(tuán)隊(duì)中有資質(zhì)的成員，但保留對(duì)臨床研究的責(zé)任（另見7.6）。這也適用于當(dāng)主要研究者將研究外包給外部組織時(shí)，在這種情況下，他/她應(yīng)執(zhí)行相關(guān)流程以確保外部組織對(duì)所有任務(wù)執(zhí)行和數(shù)據(jù)生成的完整性。

 

10.2.Qualification of the principal investigator主要研究者的資格

 

The principal investigator shall

 

主要研究者應(yīng)

 

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,

 

有相應(yīng)的教育、培訓(xùn)和經(jīng)驗(yàn)，根據(jù)本文件可以承擔(dān)臨床研究實(shí)施的責(zé)任；主要研究員的資格證明應(yīng)通過最新的簡歷或其他相關(guān)文件向申辦者提供，

 

NOTE：National regulations can also apply.

 

注：國家法規(guī)也可以適用。

 

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

 

在相關(guān)應(yīng)用領(lǐng)域有經(jīng)驗(yàn)，是否接受過研究器械使用培訓(xùn)應(yīng)考慮在內(nèi)，

 

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，包括財(cái)務(wù)沖突，會(huì)干擾臨床研究或結(jié)果解釋的利益沖突，以及

 

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

 

了解獲取知情同意的方法。

 

10.3.Qualification of investigation site研究中心的資格

 

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

 

主要研究者應(yīng)能夠證明擬參研的研究中心

 

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

 

在約定的招募期內(nèi)，有所需數(shù)量的合格受試者，

 

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,

 

有相應(yīng)教育、培訓(xùn)和經(jīng)驗(yàn)的研究團(tuán)隊(duì)可以根據(jù)本文件承擔(dān)臨床研究實(shí)施的責(zé)任；研究團(tuán)隊(duì)的資格證明應(yīng)通過最新的簡歷或其他相關(guān)文件向申辦者提供，

 

NOTE：National regulations can also apply.

 

注：國家法規(guī)也可以適用。

 

c) has adequate facilities.

 

有足夠的設(shè)施。

 

10.4.Communication with the EC與倫理委員會(huì)溝通

 

The principal investigator shall

 

主要研究者應(yīng)

 

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,

 

向申辦者提供主要研究者和倫理委員會(huì)之間任何臨床研究相關(guān)溝通內(nèi)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，在招募受試者并實(shí)施所有后續(xù)修訂之前，獲得倫理委員會(huì)對(duì)臨床研究的書面批準(zhǔn)/贊同意見，并確保申辦者已經(jīng)得到監(jiān)管機(jī)構(gòu)的批準(zhǔn)，并在必要時(shí)通知倫理委員會(huì)，

 

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

 

按照10.8中規(guī)定進(jìn)行安全報(bào)告(不良事件分類見附件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,

 

及時(shí)報(bào)告任何影響受試者權(quán)利、安全、福祉，或臨床研究科學(xué)完整性的研究方案偏離，包括在緊急情況下發(fā)生的研究方案偏離，

 

NOTE：National regulations can also apply.

 

注：國家法規(guī)也可以適用。

 

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

 

依據(jù)第8章節(jié)通知臨床研究的暫停、提前結(jié)束或常規(guī)關(guān)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.

 

在特殊情況下，申辦者可以部分或全部與倫理委員會(huì)進(jìn)行的溝通，在這種情況下，申辦者應(yīng)隨時(shí)通知主要研究者。

 

10.5.Informed consent process知情同意過程

 

The principal investigator shall

 

主要研究者應(yīng)

 

a) comply with the requirements specified in 5.8,

 

遵從5.8節(jié)所述的要求，

 

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

 

確保在獲得知情同意的過程中遵守倫理原則，以及

 

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

 

如果指定授權(quán)指定人員執(zhí)行知情同意過程，確保進(jìn)行適當(dāng)?shù)呐嘤?xùn)并記錄。

 

NOTE：Regulatory requirements can apply.

 

注：國家法規(guī)也可以適用。

 

10.6.Compliance with the CIP臨床研究計(jì)劃的依從性

 

The principal investigator shall

 

主要研究者應(yīng)

 

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

 

以書面形式確認(rèn)其認(rèn)可臨床研究計(jì)劃，

 

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

 

依據(jù)臨床研究計(jì)劃執(zhí)行臨床研究，

 

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,

 

在整個(gè)臨床研究過程中創(chuàng)建和維護(hù)源文件，并在監(jiān)查訪視或稽查期間根據(jù)要求提供這些文件，并維護(hù)該文件的類型和這些源文件的位置，

 

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,

 

確保研究器械僅由7.2節(jié)定義的經(jīng)授權(quán)的用戶，并依從臨床研究計(jì)劃和說明使用的要求使用，

 

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

 

向申辦者建議對(duì)臨床研究計(jì)劃，或研究器械，或研究器械的使用進(jìn)行任何適當(dāng)?shù)男薷模?/span>

 

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

 

如必要，在未經(jīng)申辦者、倫理委員會(huì)和監(jiān)管機(jī)構(gòu)同意的情況下，不得對(duì)臨床研究計(jì)劃進(jìn)行任何修改，

 

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

 

記錄并解釋在臨床研究過程中發(fā)生的任何與已批準(zhǔn)的臨床研究計(jì)劃有關(guān)的偏離，

 

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

 

確保有足夠的研究團(tuán)隊(duì)和設(shè)施，并在臨床研究期間得到維護(hù)和記錄，

 

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

 

確保與臨床研究評(píng)估相關(guān)設(shè)備的維護(hù)和校準(zhǔn)得到適當(dāng)?shù)膱?zhí)行和記錄，如適用，

 

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

 

確保在病例報(bào)告表和所有要求報(bào)告給申辦者的數(shù)據(jù)是準(zhǔn)確性、完整性、可讀性和及時(shí)性，

 

k) maintain the device accountability records,

 

維護(hù)器械的管理記錄

 

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,

 

遵守安全返還研究器械的流程，包括有潛在危險(xiǎn)的器械。如果報(bào)告器械缺陷，與申辦者一道提供必要的信息，以便在適當(dāng)情況下進(jìn)行準(zhǔn)確分析，

 

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

 

允許并支持申辦者執(zhí)行監(jiān)查和稽查活動(dòng)，

 

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

 

在監(jiān)查訪視期間，能夠與監(jiān)查員接觸并回答問題，

 

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

 

確定原因并實(shí)施適當(dāng)?shù)募m正和預(yù)防措施，以解決重要的不合規(guī)問題，

 

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

 

允許并支持監(jiān)管機(jī)構(gòu)和倫理委員會(huì)執(zhí)行稽查活動(dòng)，

 

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

 

確保所有臨床研究相關(guān)記錄保存按照8.3的規(guī)定執(zhí)行，

 

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

 

按照8.4中的規(guī)定簽署臨床研究報(bào)告。

 

10.7.Medical care of subjects受試者的醫(yī)療保健

 

The principal investigator shall

 

主要研究者應(yīng)

 

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,

 

如知情同意書所述，當(dāng)受試者出現(xiàn)不良事件時(shí)，應(yīng)在受試者參與臨床研究期間和之后，向受試者提供充分的醫(yī)療保健，

 

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

 

告知受試者的任何可能引起的不良事件的性質(zhì)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,

 

當(dāng)由受試者使用或操作研究器械時(shí)，應(yīng)向受試者提供關(guān)于正確使用、處理、儲(chǔ)存和歸還研究器械的必要說明，

 

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,

 

告知受試者在臨床研究過程中發(fā)現(xiàn)的任何新的重要發(fā)現(xiàn)，包括是否需要額外的醫(yī)療保健，

 

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,

 

為受試者提供與臨床研究相關(guān)的可能的緊急情況時(shí)的明確操作流程，并為緊急治療做出必要的安排，包括盲態(tài)臨床研究的揭盲流程，

 

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

 

確保臨床記錄清晰以表明受試者參加了某一特定的臨床研究，

 

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),

 

如果適用，提供臨床研究招募受試者的方法，以及伴隨治療措施的確認(rèn)和依從性（應(yīng)提供聯(lián)系地址和電話號(hào)碼），

 

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

 

在受試者同意的情況下，告知受試者的私人醫(yī)生受試者參與臨床研究的情況，

 

NOTE：National regulations can apply.

 

注：國家法規(guī)也可以適用。

 

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.

 

在充分尊重受試者的意見的同時(shí)，盡一切合理的努力來確定受試者提前退出臨床研究的原因。

 

10.8.Safety reporting安全性報(bào)告

 

The principal investigator shall

 

主要研究者應(yīng)

 

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

 

記錄每一個(gè)不良事件和觀察到的器械缺陷，并進(jìn)行評(píng)估（不良事件分類，見附件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,

 

在沒有合理延期的情況下，應(yīng)向申辦者報(bào)告所有可能導(dǎo)致嚴(yán)重的器械不良反應(yīng)的嚴(yán)重不良事件和器械缺陷；應(yīng)及時(shí)提供這些信息的詳細(xì)書面報(bào)告，如臨床研究計(jì)劃中的規(guī)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,

 

如果臨床研究計(jì)劃或倫理委員會(huì)有要求，應(yīng)向倫理委員會(huì)報(bào)告可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的嚴(yán)重不良事件和器械缺陷，

 

NOTE 1：National regulations can also apply.

 

注：國家法規(guī)也可以適用。

 

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

 

向監(jiān)管機(jī)構(gòu)報(bào)告可能導(dǎo)致器械相關(guān)嚴(yán)重不良反應(yīng)的嚴(yán)重不良事件和器械缺陷，

 

NOTE 2：National regulations can apply.

 

注：國家法規(guī)也可以適用。

 

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

 

根據(jù)申辦者的要求，向其提供與特定安全性事件報(bào)告相關(guān)的任何額外信息。