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 MEDDEV 2.7/1 revision 4 June 2016
GUIDELINES ON MEDICAL DEVICES 医疗器械指南 CLINICAL EVALUATION:
A GUIDE FOR MANUFACTURERS AND NOTIFIED BODIES UNDER DIRECTIVES 93/42/EEC and 90/385/EEC
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）
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
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
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 \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.
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）