MEDDEV 2.12-2上市后临床跟踪指南

EUROPEAN COMMISSION DG ENTERPRISE Directorate G

GUIDELINES ON POST MARKET CLINICAL FOLLOW-UP

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 were circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interested parties in the medical devices sector.

该指南是在实施欧盟医疗器械指令过程中所遇到问题的系列指南中的一个，这些指南与指令之间没有法律效力的关联，这些指南是在通过对利益相关方（包括主管当局、委员会服务机构、行业以及其他利益相关各方）进行详尽的征询后谨慎起草的。在这个过程中，草稿被传阅，相关的建议在文件中加以吸收。因此，该文件体现了医疗器械各相关方代表的立场。 Foreword : Rationale and Goals of PMCF

This document is intended to be a guide for manufacturers and notified bodies on how to carry out PMCF in order to fulfill post market surveillance obligation according to point 3. 1 of annex II, point 3. of annex IV, point 3 of annex V, point 3.1 of annex VI or point 4 of annex VII of medical device directive (add ref. AIMDD)

While clinical evidence is an essential element of the premarket conformity assessment process, it is important to recognize the limitations inherent to these premarket clinical investigations. The extent of the data that can be gathered in the premarket phase does not enable the manufacturer to detect infrequent complications or problems only apparent after widespread use, or /long term performance issues. As part of the manufacturer‟s quality system, a program of appropriate post market surveillance is key to identifying and investigating risks associated with the use of medical devices placed on the market.

前言：PMCF 的依据及目标

本文件的目的是为制造商以及公告机构开展PMCF 提供指导，以满足医疗器械指令附录II3.1，附录IV3，附录V3，附录VI3.1或附录VII4所要求的上市后市场监督义务。 虽然临床证据是对上市前合格评定程序的基本要素，重要的是要认识到上市前临床调查固有的局限性。在上市前阶段所收集到的临床数据的程度不能使制造商发现罕见的并发症或是仅有在经过长期使用后才呈现的问题，以及长期的性能问题。作为制造商质量管理体系的一部分，一个适宜的上市后监督程序的关键是识别及调查与投放市场的医疗器械的使用相关的风险。

Manufacturers should have general systems in place to cover PMS as well as having a defined

PMS strategy for each of their products/product ranges

Therefore, PMCF appears as a method of choice for this purpose. It will, for instance, enable patients' access to new therapies while establishing a review process for long term safety follow-up and detection of possible emergent risks that cannot be adequately detected by relying solely on pre-market clinical investigations (given the relatively short follow up required) or product experience /vigilance.

制造商应建立一个覆盖上市后监督的普遍体系，并且对于他们的每一个产品/产品范围都应有一个明确定义的上市后监督策略。

因此，PMCF 是为达到这一目的可选的方法之一。例如，在对仅依靠单一的上市前临床调查（由于相对短的需求跟踪）或产品经验/警戒系统不能有效发现的紧急风险进行长期的安全跟踪及侦查期间，建立一个审查程序，它将使病人获得新的疗法。

Implementation

Post market surveillance may include a number of strategies in addition to complaint handling and vigilance :

a ctive supervision by customer surveys, i nquiries of users and patients, l iterature reviews,

P ost market Clinical Follow-up, etc..

Post market clinical follow-up (PMCF) through clinical studies and registries has a great importance among these strategies. 实施

上市后监督除了处理抱怨和警械系统还可以包括很多形式，例如： 1. 通过顾客调查积极管理 2. 用户和患者调查， 3. 文献评论，

4. 上市后的临床跟踪等。

在这些形式中，上市后临床跟踪通过临床研究和登记是很重要的。

Post Market Clinical Follow-up (PMCF) should always be considered for devices where identification of possible emerging risks and the evaluation of long term safety and performance are critical. In identifying such emerging risk, the following criteria should be taken into account : • innovation , when the design of the device, the material, the principles of operation, the technology, or the medical indication is new

• severity of the disease,

• sensitive target population • risky anatomical location

• well known risk from the literature

• well known risk of similar marketed devices

• Identification of an acceptable risk during pre-CE clinical evaluation, which should be monitored in a longer term and/or through a larger population.

• Obvious discrepancy between the premarket follow up timescales and the expected life of the product

当对可能出现的风险和长期的安全以及性能评估的识别至关重要时，器械的上市后临床跟踪（PMCF ）应该被考虑。在识别这种风险时，应考虑以下方面的准则： •当设备的设计，材料，操作原理，技术，或是医疗特征采用新方法 •严重的疾病， •敏感目标人群 •危险的解剖位置

•众所周知的来源于文献的风险 •众所周知的已上市类似器械的风险

•识别在CE 认证之前的临床评估中需要很长期和/或需要通过对很多人进行测量的可接受风险。

•上市前跟进时间与产品的预期寿命之间的明显差异。

All PMCF should be planned. The PMCF plan can take the form of extended follow-up of patients enrolled in the pre-market trials, and / or a prospective study of a representative subset of patients after the device is placed on the market. It can also take the form of open registries. This plan will need to take into account :

• Results of the clinical investigation including Adverse events identified • Average life expectancy of the device

• The claims made by the manufacturer for the device • Performances for which equivalence is claimed • New information becoming available

PMCF, when carried out, must always be performed for the use of the product within its intended indications according to Instructions for use. National regulations on post market clinical studies must be taken into account.

应计划所有的上市后临床跟踪。该PMCF 计划可以采取对上市前试验所涉及病人进行持续观察和/或对在器械投放市场后具有代表性的一部分患者进行前瞻性研究的形式，也可采取开放登记的形式。计划应考虑以下方面内容： •临床调查结果，包括发现的不良事件 •设备的预期平均寿命 •制造商对器械进行的声明 •声明的性能 •可获得的新信息

实施PMCF 时，必须始终依据使用说明书在产品的预定适用范围内使用产品。有关上市后临床研究的国家法规必须加以考虑。

The involved Notified Body should review the appropriateness of the manufacturer's general PMS procedures, incorporating PMCF, as relevant, as well their PMCF plan(s) and results for specific products as part of conformity assessment procedures and quality management system auditing The follow up duration should take into account the average life expectancy of the product in its indication. Therefore, in case of a device subject to short term premarket follow up and intended

to stay in the patient for its lifetime, a longer follow up will be required.

PMCF will not be required for products for which the long term clinical performance and safety is already known from previous use of the device. In the case the assessment of a product is performed through the concept of equivalence , PMCF should always be considered .

所涉及的公告机构应审核制造商的一般上市后监督程序的适宜性，包括上市后临床跟踪，相关的特殊产品的上市后临床跟踪的计划及结果，作为合格性评价程序和质量管理体系审核的一部分。

跟进期间应将产品在其指征中的平均寿命期限考虑在内。因此，如果一个器械上市前跟踪进行了很短时间并且预期在患者体内停留整个寿命期，将需要长时间的跟踪。

产品的长期临床性能和安全在使用产品之前已经知道，将不需要上市后临床跟踪。如果产品的评估通过实质性等同的方式进行的，应经常考虑上市后临床跟踪。

Post Market clinical Requirements (Risk based matrix)

The following table sets out a „triage approach‟ and suggests general advice for the evaluation of products under different circumstances.

Notified bodies should be part of the decision making with the manufacturer if applicable.

上市后临床需求（基于风险模式）

以下表格中给出了一个“分流方法”，并提出在不同情况下对产品进行评估的一般意见。 如果适宜公告机构应当是同制造商做出决定的一部分。

*Equivalence has been precisely defined and should be demonstrated according to the criteria described in th e document “Evaluation of clinical data: A guide for manufacturers and notified bodies” (see annex 1 of this document).

*实质性等同已被明确定义，并且已根据文件“临床数据评估：制造商和公告机构指南”（见本文件附录1）中描述的准则进行证明。

ANNEX 1 : The Demonstration of equivalence （同价的证明）

依据MEDDEV 2.7.1 关于临床医疗器械的评价：认证机构与制商造的指南 4.3.1章 相关的数据；

From MEDDEV.2.7.1 : guidelines on medical devices Evaluation of clinical data : a guide for manufacturers and notified bodies -Section 4.3.1 d)relevance of data

制造商必须证明在下列方面必要的性能必须是等价的。下列出版的报告意味着： The manufacturer must demonstrate equivalence in all the following essential characteristics with the device, which is the subject of the published reports. Equivalence means : Clinical: 临床方面

使用相同的临床条件或目的

-used for the same clinical condition or purpose; -used at the same site in the body; 在人体中使用相同的位置；

-used in similar population (including age, anatomy, physiology);

使用相似的人群（包括：年龄、解剖与生理学）

-have similar relevant critical performance according to expected 具有相似的关键性的性能与期望

clinical effect for specific intended use. 明确预期使用的临床效果 Technical: 技术方面 在相似的使用条件下使用

-used under similar conditions of use;

具有相似说明和性能（力学性能、粘性、表面特性） -have similar specifications and property (e.g. tensile strength, viscosity, surface characteristics)

-be of similar design; （相似的设计）

-use similar deployment methods (if relevant); （相似的开发方法） -have similar principles of operation （相似的操作原理）

对于等同，医疗器械应当有相似的临床、技术和生物学原理，应特别注意性能、操作原理和材料，在这些之中不同之处，应当识别，评价和证明签属安全和性能方面的文件； To be equivalent, the devices should have similarity with regard to the clinical, technical and biological parameters with special attention to the performance, principles of operation and materials; or if there are differences identified, an assessment and demonstration of the significance these might have on safety and performance must be documented. 例如：

For example, where the device under consideration and the device referred to in the published study has a new principle of operation, then the two devices cannot be considered equivalent. A new mechanism and action does not necessarily result in a new clinical benefit and therefore a specifically designed clinical investigation will be needed to provide data to demonstrate (or otherwise) the clinical benefit of the new device