MEDDEV-2.12-2上市后临床跟踪指南

EUROPEAN COMMISSION DG ENTERPRISE Directorate G Unit 4 - Pressure Equipment, Medical Devices, Metrology MEDICAL DEVICES: Guidance document MEDDEV 2.12-2 May 2004 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 manufacturers 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 : active supervision by customer surveys, inquiries of users and patients, literature reviews, Post 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 manufacturers 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。PMCF Product specificities产品特点Required actions需要采取的行动no PMCF 不需要上市后临床跟踪Products for which the medium/long term clinical performance and safety is already known from previous use of the device , or from fully transferable experience with equivalent devices (except *) 产品的中长期临床性能和安全在使用设备之前或是在同类似器械经验中转换已经知道（除了） All received complaints and adverse events data shall be systematically reviewed, and all product related adverse events such as those described in Annex II 3.1 of the MDD must be notified to the relevant Competent Authority (ies). This includes all sources of information known by the manufacturer, including published literature. Monitoring of post market performance should take into account relevant data publicly available with similar devices especially when the CE marking was based on equivalence. 所有收到的抱怨和不良反应的数据，应系统地评价，以及所有与产品相关的，如MDD附件II 3.1的描述的不良反应事件，必须预先通知相关主管当局。这包括制造商已知的所有信息来源，包括已出版文献。上市后性能监测应考虑可获得的类似器械的相关数据，特别是当产品的CE认证基于实质性等同程序。PMCF Always considered for devices where identification of possible emerging risks and the evaluation of long term safety and performance are critical (*)Products quoted as “equivalent“ devices where reference product is subjected to PMCF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。（*）产品引用进行过上市后临床跟踪的相似器械。 Same as above , Plus Post-Market Clinical Follow-up (PMCF) in the form of follow up of all or a justifiable subset of patients already enrolled in pre-marketing Clinical Investigations; or on specific sub-groups and/or prospective study or registry of a sample of products. A formal protocol should describe the duration of PMCF; identify patient population and data to be collected. (NOTE: The manufacturer must justify the design, nature, and duration of post-marketing follow-up, having regard to any published standards) PMCF report to be provided to the relevant NB for review and to competent authority if requested. 与上述相同，增加：上市后临床跟踪以对上市前临床调查中涉及到的全部或适宜的一部分病人；或就具体分组和/或对产品样品的前瞻性研究或登记进行跟进。正式的草案中应描述上市后临床跟踪持续的时间；识别的患者群和收集的数据。（注意：制造商必须证明设计，性质和上市后跟踪持续的时间已经考虑了任何发布的标准）上市后临床跟踪报告应提交给公告机构进行审查，如果需要提交给主管当局。*Equivalence has been precisely defined and should be demonstrated according to the criteria described in the 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