MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

EUROPEAN COMMISSION

DG Internal Market, Industry, Entrepreneurship and SMEs

Consumer, Environmental and Health Technologies

Health technology and Cosmetics

备注：中文翻译中的临床调查=临床研究，评估=评价、设备=器械、数据=资料

Note

The present Guidelines are part of a set of Guidelines relating to questions of application of EC-Directives on medical Devices. They are legally not binding. The Guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts where circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interest parties in the medical devices sector. These guidelines incorporate changes introduced by Directive 2007/47/EC amending Council Directive 90/385/EEC and Council Directive 93/42/EEC.

本指南为一系列与CE—医疗器械指令应用问题相关的指南中的一部分。并不具有法律约束力。该指南在经过与各个利益方（主管当局、服务委员会、行业委员会、其他利益相关团体）进行深入协商之后谨慎拟定而成，期间对中期草案进行了传阅，而且部分意见还为本文件所采纳。因此，本文件反映出了来自医疗器械行业的利益团体代表所持的立场。本指南包含了指令 2007/47/EC对90/385/EEC和 93/42/EEC修正中的变更

（没规定实施时间）

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

MEDICAL DEVICES DIRECTIVES

CLINICAL INVESTIGATION

CLINICAL EVALUATION:

A GUIDE FOR MANUFACTURERS AND NOTIFIED BODIES

UNDER DIRECTIVES 93/42/EEC and 90/385/EEC

Index

1. Introduction (4)

2. Scope (4)

3. References (4)

4. Definitions (5)

5. Abbreviations (8)

6. General principles of clinical evaluation (9)

6.1. What is clinical evaluation? (9)

6.2. When is clinical evaluation undertaken and why is it important? (10)

6.2.1. Clinical evaluation undertaken for the development of a medical device (10)

6.2.2. Clinical evaluation for initial CE-marking (11)

6.2.3. Updating the clinical evaluation (11)

6.3. How is a clinical evaluation performed? (13)

6.4. Who should perform the clinical evaluation? (14)

7. Definition of the scope of the clinical evaluation (Stage 0) (15)

8. Identification of pertinent data (Stage 1) (17)

8.1. Data generated and held by the manufacturer (17)

8.2. Data retrieved from literature (18)

9. Appraisal of pertinent data (Stage 2) (19)

9.1. General considerations (19)

9.2. The appraisal plan (20)

9.3. Conduct of the appraisal (20)

9.3.1. How to evaluate methodological quality and scientific validity (20)

9.3.2. How to determine the relevance of a data set for the clinical evaluation (24)

9.3.3. How to weight the contribution of each data set (26)

10. Analysis of the clinical data (Stage 3) (27)

10.1. General considerations (27)

10.2. Specific considerations (27)

10.3. Where demonstration of conformity based on clinical data is not deemed appropriate (29)

11. The clinical evaluation report (CER, Stage 4) (29)

12. The role of the notified body in the assessment of clinical evaluation reports (31)

Appendices (32)

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

A1. Demonstration of equivalence (32)

A2. When should additional clinical investigations be carried out? (34)

A3. Device description - typical contents (35)

A4. Sources of literature (36)

A5. Literature search and literature review protocol, key elements (37)

A5.1. Background to the literature search and the literature review (38)

A5.2. Objective (38)

A5.3. Methods (39)

A6. Appraisal of clinical data - examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety (39)

A7. Analysis of the clinical data - compliance to specific Essential Requirements (41)

A7.1. Conformity assessment with requirement on safety (MDD ER1 / AIMDD ER1) (41)

A7.2. Conformity assessment with requirement on acceptable benefit/risk profile

(MDD ER1 / AIMDD ER1) (42)

A7.3. Conformity assessment with requirement on performance (MDD ER3 / AIMDD ER2) (46)

A7.4. Conformity assessment with requirement on acceptability of undesirable side-effects (MDD ER6 / AIMDD ER5) (47)

A8. Devices for unmet medical needs - aspects to consider (48)

A9. Clinical evaluation report - proposed table of contents, examples of contents (49)

A10. Proposed checklist for the release of the clinical evaluation report (54)

A11. Information on declarations of interests (56)

A12. Activities of notified bodies (56)

A12.1. Notified body assessment of clinical evaluation by conformity assessment route (56)

A12.2. Examination of a design dossier (Annex II.4; Annex 2.4) or of a type examination dossier (Annex III; Annex 3) (57)

A12.3. Evaluation as part of quality system related procedures (61)

A12.4. Notified body specific procedures and expertise (62)

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

1. Introduction 介绍

Pursuant to 依据

- section 6a of Annex I to Directive 93/42/EEC (amended by Directive 2007/47/EC) and to

- section 5a of Annex 1 to Directive 90/385/EEC (amended by Directive 2007/47/EC),

the demonstration of conformity with Essential Requirements for a medical device must include a clinical evaluation, which is conducted in accordance with Annex X to Directive 93/42/EEC or with Annex 7 to Directive 90/385/EEC.

MDD 指令93/42/EEC (amended by Directive 2007/47/EC) 附录I的6a部分和

MDD指令90/385/EEC (amended by Directive 2007/47/EC) 附录I的5a部分

和医疗器械的基本要求一致性的证明必须包含临床评价，根据Directive 93/42/EEC的附录10和Directive 90/385/EEC的附录7来指导。

This document promotes a common approach to clinical evaluation for medical devices regulated by directives 90/385/EEC and 93/42/EEC. It does not concern in vitro diagnostic devices.

The depth and extent of clinical evaluations should be flexible and appropriate to the nature, intended purpose, and risks of the device in question. Therefore, this guidance is not intended to impose device-specific requirements.

这个文件提供了按directives 90/385/EEC and 93/42/EEC规定开展医疗器械临床评价的一般途径，不包含体外诊断试剂。

This document uses the terms "must", "shall", "have to" where these terms are used in the Directives. "Should" is used in other instances.

本文档使用了术语“必须”、“应当”、“必须”这些术语使用的指令。“应该”在其他情况下使用。2. Scope范围

This guide is not legally binding; only the text of the Directives is authentic in law. It is recognised that under given circumstances, for example as a result of scientific developments, an alternative approach may be possible or appropriate to comply with the

legal requirements.

本指南不具有法律约束力，只有在指令的文本是法律约束的。在给定的情况下是被承认

的，例如作为科学发展的结果，另一种方法可能或适当的符合法律要求。

Nevertheless, due to the participation of interested parties and of experts from national Competent Authorities, it is anticipated that this guide will be followed within the Member States, thereby supporting uniform application of relevant provisions of EU Directives and common practices.

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

然而，由于有利害关系人和国家主管部门的专家参与，预计本指南将在成员国跟从，从而支持欧盟相关指令的统一应用和一般做法。

On certain issues not addressed in the Directives, national legislation may be different from this guide.

在指令中，某些问题不能被解决，国家法规可能不同于本指南。

This guide is regularly updated according to regulatory developments. The latest version of the guide should always be used. This version is a complete revision of the previous texts. The medical device legislation in Europe is currently being significantly revised. A new Regulation of the European Parliament and of the Council on medical devices will be published, which may result in changes to important concepts or definitions relating to clinical evaluation. Parts or all of this document are likely to be revised. Some contents (such as contents about notified bodies) are likely to be removed and integrated in other series of documents.

本指南将根据监管发展而定期更新，指南的最新版本总是被使用。本版本完全修订了之前的文本。

欧洲的医疗器械法规目前正在大幅修订。一项新规定的欧洲议会和理事会的医疗设备将发布，这可能导致临床评估相关的重要概念或定义发生变化。部分或全部本文档可能会修订。某些内容(如关于NB的内容)可能会被删除和综合其他系列文档中。

3. References 参考文献

European Legislation: 欧盟法规

- Council Directive 90/385/EEC of 20 June 1990 relating to active implantable medical devices

AIMDD 90/385/EEC

- Council Directive 93/42/EEC of 14 June 1993 concerning medical devices

MDD 93/42/EEC

- Commission Regulation 722/2012 of 8 August 2012 concerning active implantable medical devices and medical devices manufactured utilising tissues of animal origin

（有源植入器械和含动物源组织器械的法规）

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

- Commission Implementing Regulation 920/2013 of 24 September 2013 on the designation and the supervision of notified bodies under Council Directive 90/385/EEC on active implantable medical devices and Council Directive 93/42/EEC on medical devices

Harmonised and International standards: 协调标准和国际标准

- EN ISO 14155:2011 Clinical investigation of medical devices for human subjects –Good clinical practice

EN ISO 14155:2011 人体用医疗器械的临床调查—优良的临床规范

- EN ISO 14971:2012 Medical devices –application of risk management to medical devices

EN ISO 14971:2012 医疗器械–风险管理对医疗器械的应用

European guidance documents: 欧盟指南文件

- MEDDEV 2.12/1 Guidelines on a medical devices vigilance system

MEDDEV 2.12/1 医疗器械警戒系统指南

- MEDDEV 2.12/2 Guidelines on post market clinical follow-up studies: a guide for manufacturer and notified body

MEDDEV 2.12/2 上市后的临床跟踪指南

- MEDDEV 2.4/1 Classification of medical devices

MEDD EV 2.4/1 医疗器械的分类

- MEDDEV 2.7/2 Guidelines for competent authorities for making a validation/assessment of a clinical investigation application under directives 90/385/EEC and 93/42/EC

MEDDEV 2.7/2 主管部门进行临床研究应用的验证/评估指南

- Manual on borderline and classification in the Community regulatory framework for medical devices

人工边界和分类，医疗器械在社区的监管架构

- NBOG BPG 2006-1 Change of notified body

NBOG BPG 2006-1 公告机构的变更

- NBOG BPG 2009-1 Guidance on design-dossier examination and report content

NBOG BPG 2009-1 设计档案检查和报告内容的指南

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

- NBOG BPG 2009-4 Guidance on notified body‘s tasks of technical documentation assessment on a representative basis

NBOG BPG 2009-4 公告机构技术文件评估指南

- NBOG BPG 2010-2 Guidance on audit report content

NBOG B PG 2010-2 审计报告内容指南

- NBOG BPG 2014-1 Renewal of EC design-examination and type-examination certificates: Conformity assessment procedures and general rules

NBOG BPG 2014-1 EC设计审核和型式检验认证：符合性评估程序和一般规则

- NBOG BPG 2014-2 Guidance on the information required for notified body medical device personnel involved in conformity assessment activities

NBOG BP G 2014-2 公告机构医疗设备人员参与合格评定活动所需信息的指南

- NBOG BPG 2014-3 Guidance for manufacturers and notified bodies on reporting of design changes and changes of the quality system

NBOG BP G 2014-3 制造商和公告机构报告设计变更和质量体系变更的指南

Other guidance documents:其他指南文件

- GHTF SG5 N1R7:2007: Clinical evidence - Key definitions and concepts

GHTF S G5 N1R7:2007 临床证据—关键定义和概念

- GHTF SG5 N2R8:2007: Clinical evaluation 临床评价

- GHTF SG5 N41R9:2005: Essential principles of safety and performance GHTF SG5 N41R9:2005: 安全和有效的基本原则

This list contains documents available at the time this MEDDEV document was published. In general, the most recent versions of standards and legal texts should be used.

这个列表包含文件时可用MEDDEV文档发表。一般来说，应当使用最新版本的标准和法律文本。

4. Definitions 定义

4.1 Adverse event: any untoward medical occurrence, unintended disease or injury, or any untoward clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not related to the investigational medical device.

不良事件：任何不幸的医疗事件，非预期的疾病或伤害，或任何不幸的临床症状（包括反常的试验检查）在受试者、使用者、或无论是否与临床实验的医疗设备相关的其他人员。

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

NOTE 1: This includes events related to the investigational device or the comparator.

包括相关的调查设备和对照设备

NOTE 2: This includes events related to the procedures involved.

NOTE 3: For users or other persons this is restricted to events related to the investigational medical device.对使用者或其他人员仅限于调查器械相关的事件。

[EN ISO 14155:2011]

4.2 Bias: bias is a systematic deviation of an outcome measure from its true value, leading to either an overestimation or underestimation of a treatme nt’s effect. It can originate from, for example, the way patients are allocated to treatment, the way treatment outcomes are measured and interpreted, and the way data are recorded and reported. [Adapted from GHTF SG5/N2R8:2007]

偏见：偏见是一个从它的真正价值和测量结果之间的系统性偏差，导致一个高估或者低估治疗的效果。可能来源于，例如病人分配给治疗的方式，治疗结果的测量和解释方式，数据记录和报告的方式。

4.3 Clinical data: the safety and/or performance information that is generated from the clinical use of a device. Clinical data are sourced from:

由医疗器械的临床使用生成的安全和/或性能信息，临床数据包括：

- clinical investigation(s) of the device concerned; or设备有关的临床调查，或

- clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or临床调查或科学文献的研究报告，或者类似设备的等价性问题可以被证明，或

- published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated.公开发表或未公开发表的相同设备或者等价性问题可以被证明相似设备的临床经验报告

[derived from Article 1.2.k MDD and Art. 1.2.k AIMDD]

4.4 Clinical evaluation: a methodologically sound ongoing procedure to collect, appraise and analyse clinical data pertaining to a medical device and to evaluate whether there is sufficient clinical evidence to confirm compliance with relevant essential requirements for safety and performance when using the device according to the manufacturer’s Instructions for Use.

临床评价：不间断收集、评价和分析适合于医疗器械的临床数据，评价是否足够充分的临床

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

证据来确认在根据制造商的使用说明书使用设备时，符合相关安全和性能相关的基本要求。

Note: In exceptional cases where an instruction for use is not required, the collection, analysis and assessment are conducted taking into account generally recognised modalities of use. 在一个不需要使用说明书的特殊情况下，收集、分析和评估考虑采用普遍认可的使用形式。

4.5 Clinical evidence: the clinical data and the clinical evaluation report pertaining to a medical device. [GHTF SG5/N2R8:2007]

临床证据: 适合于医疗器械的临床数据和临床评价报告

4.6 Clinical investigation: systematic investigation in one or more human subjects, undertaken to assess the safety or performance of a medical device.

临床调查：在一个或多个人体受试者上进行的任何系统调查, 用于评估医疗器械的安全和/或

性能。

Note: 'clinical trial' or ' clinical study' are synonymous with ' clinical investigation'. [EN ISO 14155:2011]clinical trial 等同于 clinical study

4.7 Clinical investigation plan: document that states the rationale, objectives, design and proposed analysis, methodology, monitoring, conduct and record-keeping of the clinical investigation. [EN ISO 14155:2011]

临床调查方案：陈述基本原理，目标，设计和建议的分析、方法论、监测、进行和记录临床

调查的文件

4.8 Clinical performance: behaviour of a medical device or response of the subject(s) to that medical device in relation to its intended use, when correctly applied to appropriate subject(s). [EN ISO 14155:2011]

临床性能: 医疗器械正确应用于合适的受试者，医疗器械的行为或者响应达到预期用途

4.9 D evice regist ry: an organised system that uses observational study methods to collect defined clinical data under normal conditions of use relating to one or more devices to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure and that serves predetermined scientific, clinical or policy purpose(s).

器械登记：一个组织系统，采用观察性研究方法来收集定义的临床数据，在正常使用情况下

有关指定一个或多个设备评估结果，为一个特定的疾病、条件定义的人口或暴露和预定服务

科学、临床或政策目的(s)。

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

Note: The term “device registry” should not be confused with the concept of device registration and listing.

[MEDDEV 2.12/2 rev2]

4.10 Clinical safety: freedom from unacceptable clinical risks, when using the device according to t he manufacturer’s Instructions for Use. [MEDDEV 2.7/2 revision 2]

Note: In exceptional cases where an instruction for use is not required, the collection, analysis and assessment are conducted taking into account generally recognised modalities of use.

临床安全: 当根据说明书使用器械时，没有不可接受的临床风险。

4.11 Clinical use: use of a medical device in or on living human subjects.

Note: Includes use of a medical device that does not have direct patient contact.

临床使用：医疗器械在人类活体上使用

4.12 E quivalent device: a device for which equivalence to the device in question can be demonstrated. [Derived from Art. 1.2.k MDD]

等价器械：一个器械的等同性问题能被证明的器械。

4.13 Feasibility study: a clinical investigation that is commonly used to capture preliminary information on a medical device (at an early stage of product design) to adequately plan further steps of device development, including needs for design modifications or parameters for a pivotal study. [MEDDEV 2.7/2 revision 2]

可行性研究：临床调查通常用于获取医疗设备初步信息(在产品设计的早期阶段)而充分计划设备开发的未来步骤，包括需要设计修改或一个关键参数研究。

4.14 H armonised standard s: standards whose references have been published in the Official Journal of the European Communities. [Derived from article 5 of Directive 90/385/EEC and article 5 of Directive 93/42/EEC]

协调标准：已经发表在欧洲共同体的官方杂志上的应用标准。

4.15 Hazar d: potential source of harm. [EN ISO 14971:2012]

危险：潜在的伤害。

4.16 Hazard due to substances and technologies: for the purpose of this MEDDEV document,

a hazard that is seen with products that share specific characteristics.

危险物质和技术：为了MEDDEV文档的目的，看作分担特定特征的产品的风险。？

Note: This includes products that contain the same materials and substances, material combinations, use the same technologies, produce similar abrasion, are used with the same

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

type of surgical approach, share the same manufacturing procedures or impurities, or share other characteristics.

4.17 Incident: any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labelling or the instructions for use which, directly or indirectly, might lead to or might have led to the death of a patient, or user or of other persons or to a serious deterioration in their state of health. [MEDDEV 2.12/rev 8]

事件：任何设备的品质和/或性能的故障或恶化，以及标签或使用说明书中的任何不足，直接或间接，可能导致或可能已经导致病人或使用者或他人的死亡，或他们的健康状况严重恶化。

4.18 Information materials supplied by the manufacturer：for the purpose of this document, this refers to the labelling, instructions for use and the manufacturer's promotional materials for the device under evaluation. [Derived from MDD Art. 1.2.g, MDD Annex I section 13, AIMDD Art. 1.2.f, AIMDD Annex I sections 14 and 15]

制造商提供的信息材料：本文件的目的是指的是设备标签、使用说明书和制造商的宣传材料应该评估。

4.19 Inten ded purpo se: the use for which the device is intended according to the data supplied by the manufacturer on the labelling, in the instructions and/or in promotional materials. [MDD Art. 1.2.g, AIMDD Art. 1.2.f]

预期目的：设备的使用是根据制造商提供的数据标签、说明书和/或促销材料

4.20 Investigator: individual member of the investigation site team designated and supervised by the principal investigator at an investigation site to perform critical clinical-investigation-related procedures or to make important clinical investigation-related decisions. [EN ISO 14155:2011]

研究者：

4.21 PMCF plan: the documented, proactive, organised methods and procedures set up by the manufacturer to collect clinical data based on the use of a CE-marked device corresponding to a particular design dossier or on the use of a group of medical devices belonging to the same subcategory or generic device group as defined in Directive 93/42/EEC. The objective is to confirm clinical performance and safety throughout the expected lifetime of the medical device, the acceptability of identified risks and to detect emerging risks on the basis of factual evidence. [MEDDEV 2.12/2 rev.2]

PMCF计划：

4.22 PMCF study: a study carried out following the CE marking of a device and intended to answer specific questions relating to clinical safety or performance (i.e. residual risks) of a

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

device when used in accordance with its approved labelling. [MEDDEV 2.12/2 rev.2]

PMCF研究：

4.23 Risk: combination of the probability of occurrence of harm and the severity of that harm. [EN ISO 14971:2012]风险：危害发生的概率和危害严重性的组合。

4.24 Risk m anagement: systematic application of management policies, procedures and practices to the tasks of analysing, evaluating, controlling and monitoring risk. [EN ISO 14971:2012]

风险管理：系统应用管理政策、程序和实践来分析、评价、控制和监控风险的工作。

4.25 Serious adverse event: adverse event that 严重不良事件

a) led to death,

b) led to serious deterioration in the health of the subject, that either resulted in

1) a life-threatening illness or injury, or

2) a permanent impairment of a body structure or a body function, or

3) in-patient or prolonged hospitalization, or

4) medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,

c) led to foetal distress, foetal death or a congenital abnormality or birth defect.

a) 导致死亡;

b) 导致病人，使用者或他人的健康恶化:

(1) 导致威胁生命的疾病或伤害;

(2) 导致人体结构或身体机能永久的损伤;

(3) 要求病人住院治疗或延长住院时间

(4) 导致医疗或手术的介入从而阻止对人体结构或身体机能的永久损失;

c ) 导致胎儿宫内窒息，胎儿死亡或先天不健全

NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the CIP [Clinical Investigation Plan], without serious deterioration in health, is not considered a serious adverse event. [EN ISO 14155:2011]在于其存在的情况下计划住院，或一个CIP(临床研究计划)过程所需的，没有严重的健康恶化，并不被视为严重不良事件。

4.26 Sufficient clinical evidence: an amount and quality of clinical evidence to guarantee the scientific validity of the conclusions.

MEDDEV2.71 revision 4 June 2016 Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and 90385EEC

足够的临床证据：临床证据的数量和质量保证结论的科学有效性。

5. Abbreviations 缩写词

AIMDD: Active implantable medical device directive (Council Directive 90/385/EEC amended by Directive 2007/47/EC) 有源植入医疗器械

CEAR: Clinical Evaluation Assessment Report 临床评价评估报告

CER: Clinical Evaluation Report 临床评价报告

ER: Essential Requirement 基本要求

IFU: Instructions For Use 使用说明书

MDD: Medical Device Directive (Council Directive 93/42/EEC amended by Directive 2007/47/EC) 医疗器械指令

PMS: Post Market Surveillance 上市后的监督

PMCF: Post Market Clinical Follow-Up 上市后的随访

6. General principles of clinical evaluation 临床评价的一般原则

6.1. What is clinical evaluation? 什么是临床评价

Clinical evaluation is a methodologically sound ongoing procedure to collect, appraise and analyse clinical data pertaining to a medical device and to analyse whether there is sufficient clinical evidence to confirm compliance with relevant essential requirements for safety and performance when using the device according to the manufacturer’s instructions for use.

临床评价是一种方法论，是持续的收集、评价和分析临床数据适合医疗器械的过程，和在根据制造商的使用说明书使用设备时，分析是否有足够的临床证据来证实符合相关安全和性能的基本要求。

In exceptional cases where an instruction for use is not required, the collection, appraisal, and analysis are conducted taking into account generally recognised modalities of use.

在不需要使用说明书的特殊情况下，进行收集、评价和分析考虑普遍认可的使用形式。

The requirements for clinical evaluation apply to all classes of medical devices. The evaluation should be appropriate to the device under evaluation, its specific properties, and its intended purpose.

临床评估的要求适用于所有类别的医疗设备。评价应适合设备评估它的特定属性和预期目的。Benefits and risks should be specified, e.g. as to their nature, probability, extent, duration and frequency. Core issues are the proper determination of the benefit/risk profile in the intended target groups and medical indications, and demonstration of acceptability of that profile based

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on current knowledge/ the state of the art in the medical fields concerned.

应该定收益和风险，例如他们的种类、概率、范围、持续时间和频率。核心问题是在目标群和医学指征众测定适当效益/风险预测，和基于医疗领域现有知识/科学技术下的状况证明是可接受性，。

Clinical evaluation is a responsibility of the manufacturer and the clinical evaluation report is an element of the technical documentation of a medical device.

临床评估是制造商的责任和临床评估报告是医疗设备技术文档的一部分。

For compliance with European medical device directives 需要遵守以下欧盟的医疗器械指令•the clinical evaluation addresses the following Essential Requirements:

临床评价满足下述基本原则

- Annex 1 sections 1, 2, 5 of AIMDD (for active implantable medical devices), or

AIMDD附录1的1、2、5，或

- Annex I sections 1, 3, 6 of MDD (for medical devices); MDD附录1的1、3、6

see Appendix A7 (Analysis of the clinical data - compliance to specific Essential Requirements);见附录A7（临床数据分析-符合特定的基本要求）

•the evaluation must follow defined and methodologically sound procedures as described in: 评价必须遵从下述的定义和方法论

- Annex 7 of AIMDD (for active implantable medical devices), or AIMDD附录7 或

- Annex X of MDD (for medical devices); MDD附录10

•where demonstration of conformity with essential requirements based on clinical data is not deemed appropriate, an adequate justification has to be given. The justification is included in the clinical evaluation report with contents according to:

与临床数据的基本要求相符合的证明认为不合适，必须要有充足的理由。理由包含在临床评估报告中，内容根据：

- Annex 7 section 1.5 of AIMDD (for active implantable medical devices), or

AIMDD附录7的1.5部分，或

- Annex X section 1.1d of MDD (for medical devices). MDD附录10的1.1d部分Conformity to the Essential Requirements can only be assumed when the following items are aligned with each other:符合基本要求只能假定，当下面的项目互相对准的时候？

- the information materials supplied by the manufacturer (the labelling, instructions for

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use, available promotional materials, including accompanying documents foreseen by the manufacturer)

制造商提供的信息（标签、说明书、促销资料，包括补充资料）

- the clinical evaluation (the device description used for the clinical evaluation, other contents of the clinical evaluation report)

临床评价（设备描述用于临床评价，临床评价报告的其他内容）

- the available clinical data (such as results of Clinical Investigations, publications, PMS studies, etc.). 获得的临床数据（临床调查结果、出版物、PMS研究等）

Particularly, evaluators should address if the following points are adequately supported by sufficient clinical evidence:

尤其是，评价者应该解决以下几点是否充分足够的临床证据来支持:

- the intended purpose described in the information materials supplied by the manufacturer (including for all medical indications);

制造商提供信息材料里描述的预期目的（包括所有的医学特征）

- the clinical performance and benefits described in the information materials supplied by the manufacturer (including, for example, any claims on product performance and safety); 制造商提供信息材料里描述的临床性能和收益（包括产品性能和安全的任何要求）

- measures for risk avoidance and risk mitigation described in the information materials supplied by the manufacturer (including, for example the declaration of the residual risks, contraindications, precautions, warnings, instructions for managing foreseeable unwanted situations);

制造商提供信息材料里描述的避免风险和降低风险的措施(包括,例如宣称的剩余风险、禁忌症、预防措施、警告、管理可预见的意外情况的说明);

- the usability of the device for the intended users and the suitability of the information materials supplied by the manufacturer for the intended users (including, if applicable, for lay or disabled persons);

对目标用户来说，器械的可用性和制造商提供的信息资料的适用性(包括，如果适用，外行或残疾人)

- instructions for target population groups (including, for example, pregnant women, paediatric populations).

说明目标人群(包括孕妇、婴幼儿)。

6.2. When is clinical evaluation undertaken and why is it important?

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什么时候开展临床评价和它为什么重要？

Clinical evaluation is conducted throughout the life cycle of a medical device, as an ongoing http://ually, it is first performed during the development of a medical device in order to identify data that need to be generated for market access. Clinical evaluation is mandatory for initial CE-marking and it must be actively updated thereafter.

临床评价是在医疗器械使用生命周期内持续进行的过程。它首先是在医疗器械研发期间执行，以便识别市场准入需要的数据。首次获得CE-marking时，临床评价是强制要求的，在随后需要积极更新。

Clinical evaluation is necessary and important because it ensures that the evaluation of safety and performance of the device is based on sufficient clinical evidence throughout the lifetime that the medical device is on the market. This ongoing process enables manufacturers to provide notified bodies and competent authorities with sufficient clinical evidence for demonstration of conformity of the device with the Essential Requirements throughout its lifetime (for example for CE marking, fulfilment of post-market surveillance and reporting requirements, or during surveillance procedures).

临床评价是必须的和重要的，因为确保器械的安全性和有效性得到评价，通过器械在市场上整个生命周期获得的充足的临床数据。这种持续的过程使制造商提供NB和通知主管当局有足够的临床证据来证明设备在整个生命周期满足基本要求(例如CE marking，实现上市后的监测和报告的要求，或在监测过程中)。

6.2.1. Clinical evaluation undertaken for the development of a medical device

临床评价用于医疗设备的开发

Premarket research and development are guided by clinical evaluation and risk management. Typically, manufacturers carry out clinical evaluations to

上市前的研究和开发应遵循临床评估和风险管理。通常，制造商进行临床评价

•define needs regarding clinical safety and clinical performance of the device;

定义关于器械的临床安全性和临床性能的需要

•in case of possible equivalence to an existing device, evaluate if there are clinical data available and determine equivalence; for additional information, see Appendix A1 (Demonstration of equivalence);

尽可能的等效到现有设备，评价是否有用的临床数据和确定等效性，更多信息请参阅附录A1(等效性证实)

•carry out a gap analysis and define which data still need to be generated with the device under evaluation, whether clinical investigations are necessary and if so, to define the study