MDR-EU-2017-745-欧盟医疗器械法规 -附录 14

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本文转载自“木之唐咨询”

ANNEX XIV 临床评价和上市后临床跟踪 CLINICAL EVALUATION ANDPOST-MARKET CLINICALFOLLOW-UP

第A部分：临床评价 CLINICALEVALUATION

1.       需计划、不断进行并记录临床评价，制造商应：To plan, continuously conduct and document a clinical evaluation,manufacturers shall:

a)    建立并更新临床评价计划，该计划至少应包括：establishand update a clinical evaluation plan, which shall includeat least:

标识通用安全与性能要求（需要相关临床数据的支持）；anidentification of the general safety and performance requirements that requiresupport from relevant clinical data;

器械的预期用途说明；as pecification of theintended purpose of the device;

明确预期使用者以及明确适应症和禁忌症；a clear specificationof intended target groups with clear indications and contra-indications;

对患者预期临床益处的详细说明以及相关和指定的临床结果参数；a detaileddescription of intended clinical benefits to patients with relevant andspecified clinical outcome parameters;

检验临床安全性的定性和定量方面的方法说明，并明确说明对剩余风险和副作用的确定方法；a specification of methods to be used for examination of qualitativeand quantitative aspects of clinical safety with clear reference to thedetermination of residualrisks and side-effects;

根据医学中最先进的技术确定器械各种适应症和预期用途的收益风险比的可接受性所使用的参数的指示性清单和说明；an indicative list and specification of parameters to be used todetermine, basedon the state of the art in medicine, the acceptability of thebenefit-riskratio for the various indications and for the intended purpose orpurposes ofthe device;

如何解决特定方面（如药物、非活性动物或人体组织的使用）相关的风险利益问题的指示；anindication how benefit-risk issues relating to specific components such asuseof pharmaceutical, non-viable animal or human tissues, are to be addressed;and

一份用于指示从探索性研究（如首次人体研究、可行性研究、先导研究）到验证性研究（如关键的临床研究）进展过程的临床研发计划，以及符合本附录第B部分所述的PMCF，此PMCF需列出里程碑并说明潜在验收标准；a clinical development plan indicating progression from exploratoryinvestigations,such as first-in-man studies, feasibility and pilot studies, toconfirmatory investigations, such as pivotal clinical investigations, and aPMCF as referredto in Part B of this Annex with an indication ofmilestones and a description of potential acceptance criteria;

b)         确定器械相关的可用临床资料及其预期用途，以及通过系统的科学文献检索找到临床证据的缺口；identifyavailable clinical data relevant to the device and its intended purpose andanygaps in clinical evidence through a systematic scientific literature review;

c)         通过评估临床数据在构建器械安全性和性能方面的适用性，对全部相关临床数据做出评价；appraise allrelevant clinical data by evaluating their suitability for establishing thesafety and performance of the device;

d)         根据临床研发计划，通过合理设计的临床研究，生成解决现存问题所需的任何新的或额外的临床数据；generate,through properly designed clinical investigations in accordance with theclinical development plan, any new or additional clinical data necessary toaddress outstanding issues; and

e)         分析所有相关临床数据，以便得出器械的安全和临床性能（包括临床益处）方面的结论。analyse allrelevant clinical data in order to reach conclusions about the safety andclinical performance of the device including its clinical benefits.

2.       临床评价应深入且客观，并同时兼顾有利和不利数据。其深度和程度应与所述器械的性质、分类、预期用途、制造商有关该器械的声明和风险相称。The clinical evaluation shall be thorough and objective, and takeinto account both favourable and unfavourable data. Its depth and extent shallbe proportionate and appropriate to the nature, classification, intendedpurpose and risks of the device in question, as well as to the manufacturer'sclaims in respect of the device.

3.       临床评价只能基于可证明与所述器械同等的相关器械的临床数据。在证明同等性的过程中应考虑以下技术、生物和临床特点： Aclinical evaluation may be based on clinical data relating to a device forwhich equivalence to the device in question can be demonstrated. The followingtechnical, biological and clinical characteristics shall be taken intoconsideration for the demonstration of equivalence:

技术特点：具有类似设计的器械；在类似条件下使用；具有类似规格和特性，包括物理化学特性，如能源强度、拉伸强度、粘度、表面特征、波长、软件算法等；使用类似部署方法（如相关）；具有类似工作原理和关键性能要求。Technical: the device is of similar design; is used under similarconditions of use; has similar specifications and properties including physicochemical properties suchas intensity of energy, tensile strength, viscosity,surface characteristics, wavelength and software algorithms; uses similardeployment methods, where relevant; has similar principles of operation andcritical performance requirements;

生物特点：对于类似类型、类似接触时间和类似的物质释放特征，包括降解产物和可溶出物，该器械使用相同的材料或物质接触相同的人体组织或体液。Biological: the device uses the same materials or substances incontact with the same human tissues or body fluids for a similar kind andduration of contact and similar release characteristics of substances,including degradation products and leachables;

临床特点：该器械用于同一临床情况或目的，包括类似的疾病严重程度和阶段，针对身体的同一部位，用于类似人群，包括年龄、解剖学和生理学；具有相同类型的使用者，具有根据预期临床效果得出的类似的针对某一特定预期用途的相关关键性能。Clinical: the device is used for the same clinical condition orpurpose, including similar severity and stage of disease, at the same site inthe body, in a similar population, including as regards age, anatomy andphysiology; has the same kind of user; has similar relevant criticalperformance in view of the expected clinical effect for a specific intendedpurpose.

第一段列出的特点的类似程度应使得器械的安全性和临床性能方面无显著的临床差异。对等同性的考虑必须始终基于合理的科学根据。为便于考察等同性，必须能够清楚地表明制造商有充分的条件获取具有等同性的相关器械上数据。The characteristics listed in the first paragraph shall besimilar to the extent that there would be no clinically significant differencein the safety and clinical performance of the device. Considerations ofequivalence shall be based on proper scientific justification. It shall beclearly demonstrated that manufacturers have sufficient levels of access to thedata relating to devices with which they are claiming equivalencein order to justifytheir claims of equivalence.

4.       临床评价的结果和其所基于的临床证据应记录在临床评价报告中，而此报告应作为器械符合性评估的证明。Theresults of the clinical evaluation and the clinical evidence on which it isbased shall be documented in a clinical evaluation report which shall supportthe assessment of the conformity of the device.临床证据和非临床检测方法得到的非临床数据以及其他相关文件一起，应足以允许制造商证明所述器械满足通用安全与性能要求，并应加入所述器械技术文件中。The clinical evidence together with non-clinical data generated fromnon-clinical testing methods and other relevant documentation shall allow the manufacturerto demonstrate conformity with the general safety and performance requirementsand shall bepart of the technical documentation for the device in question.

临床评价中参考的有利和不利数据也应全部包含在技术文件中。Bothfavourable and unfavourable data considered in the clinical evaluation shallbeincluded in the technical documentation.

第B部分：上市后临床跟踪 POST-MARKETCLINICAL FOLLOW-UP

5.       PMCF是一个更新本附录A部分第61条中所述的临床评价的持续过程，并应加入制造商上市后监管计划中。在进行PMCF时，制造商应主动收集并评估器械的临床数据，此器械应有CE标识，上市后或在相关符合性申请表评估流程中所述的其预期用途范围内投入使用，旨在验证在整个器械的预期使用寿命中器械的安全性和性能、确定已识别风险的持续可接受性，以及旨在基于事实证据检测新出现的风险。PMCF shall be understood to be a continuous process that updates theclinical evaluation referred to in Article 61 and Part A of thisAnnex and shall be addressed in the manufacturer's post-marketsurveillance plan. When conducting PMCF, the manufacturer shall proactivelycollect and evaluate clinical data from the usein or on humans of a devicewhich bears the CE marking and is placed on the market or put into servicewithin its intended purpose as referred to in the relevant conformityassessment procedure, with the aim of confirming the safety and performancethroughout the expected life time of the device, of ensuring the continuedacceptability of identified risks and of detecting emerging risks on the basisof factual evidence.

6.       PMCF的执行应当遵循PMCF计划中规定并记录的方法。PMCF shall be performed pursuant to a documented method laid down ina PMCF plan.

6.1   PMCF计划应规定方法和程序，以便主动收集和评估临床数据，旨在 ThePMCF plan shall specify the methods and procedures for proactively collectingand evaluating clinical data with the aim of:

a)       确认器械在其预期使用寿命内的安全性和性能，confirming the safety andperformance of the device throughout its expected lifetime,

b)      识别之前未知的副作用并监控已识别的副作用和禁忌症，identify in gpreviously unknownside-effects and monitoring the identified side-effects and contraindications,

c)       在事实证据的基础上标识并分析突发风险，identifying and analysing emergentrisks on the basis of factual evidence,

d)      确保在附录I第1节和第9节中所述的收益/风险比的持续可接受性，以及ensuring the continued acceptability of the benefit-risk ratio referredto in Sections 1and 9 of Annex I, and

e)       确定器械可能的操作不当或超出标示使用，以验证其预期用途是否正确。identifying possiblesystematic misuse or off-label use of the device, with a view to verifying thatthe intended purpose is correct.

6.2   PMCF计划至少应包含： The PMCF plan shall includeat least:

1.   待采用的PMCF的通用方法和流程，如收集所获得的临床经验和使用者反馈，筛选科学文献和临床数据的其他来源；the general methods and procedures of the PMCF to be applied, suchas gathering of clinical experience gained, feedback from users, screening ofscientific literature and of other sources of clinical data;

2.   待采用的PMCF的专用方法和流程，如对相应注册人员或PMCF研究的评估；the specific methods and procedures of PMCF to be applied, such asevaluation of suitable registers or PMCF studies;

3.   和（b）中所述的方法和流程的适当理由；a rationalefor the appropriateness of the methods and procedures referred to inpoints (a)and (b);4.   对第4节中所述的临床评价报告相关部分和附录I第3节中所述的风险管理的引用；a reference to the relevantparts of the clinical evaluation report referred to in Section

4 and to the risk management referred to in Section 3 ofAnnex I;需通过PMCF完成的具体目标；the specific objectives to be addressed by the PMCF;对等同或类似器械的相关临床数据的评估，an evaluation of the clinical data relating to equivalent or similardevices;参考制造商使用的任何相关CS、协调标准和PMCF相关指南。reference to any relevant CS, harmonisedstandards when used by the manufacturer, and relevant guidance on PMCF; and对由制造商执行的PMCF活动（如对PMCF数据的分析和报告）的详细且充分合理的时间安排。a detailed and adequately justified time schedule for PMCFactivities (e.g. analysisof PMCF data and reporting) to be undertaken by themanufacturer.

7.       制造商应分析PMCF的结果，并在PMCF评估报告中记录结果，而此PMCF评估报告应加入临床评价报告和技术文件中。The manufacturershall analyse the findings of the PMCF and document the results ina PMCFevaluation report that shall be part of the clinical evaluation report and thetechnical documentation.8.       和本附录第A部分第61条中所述的临床评价中以及附录I第3节中所述的风险管理中应考虑到PMCF评估报告的结论。若通过PMCF确定了预防和/或纠正措施的必要性，则制造商应实施此等措施。The conclusions of the PMCF evaluation report shall be taken intoaccount for the clinical evaluation referred to in Article 61 and Part Aof this Annex andin the risk management referred to in Section 3 ofAnnex I. If, throughthe PMCF, the need for preventive and/or correctivemeasures has been identified, the manufacturer shall implement them.