风险管理

在临床评价计划（CEP）中，“风险管理”章节的核心目的并非重新执行风险管理活动，而是清晰阐述风险管理过程如何与临床评价活动相互关联、相互输入，并共同确保待评价医疗器械的受益风险比在预期用途下是可接受的。本章节应概述已识别的临床相关风险，以及计划如何通过临床评价来进一步确认这些风险的可控性和可接受性。

撰写本章节时，应体现风险管理与临床评价之间持续的、双向的互动关系，这是符合MDR法规要求的关键。

关联现有的风险管理框架

首先，本章节应明确指出制造商已经按照适用的标准（如ISO 14971）和MDR的要求，建立并运行了一套完整的风险管理过程。临床评价计划是在这个既定的风险管理框架基础上进行的。因此，需要概述风险管理过程是如何识别与待评价器械相关的临床风险的。通常，这些信息来源于一系列核心的风险管理文件，例如风险管理计划、危害分析（HA，可能包括使用危害分析、设计危害分析等）、过程/制造FMEA（PFMEA），以及最终的风险管理报告。在CEP中提及这些文件，能够表明临床评价所依据的风险背景是有据可查的。

临床评价中需关注的已识别风险

在阐述了风险管理的总体框架后，CEP应简要说明通过上述风险管理活动，已经识别出哪些与待评价器械临床使用相关的重大风险。这包括对这些风险（包括初始风险以及经过风险控制措施缓解后的剩余风险）的初步评估情况，以及其可接受性是如何依据风险管理计划中预设的标准（通常在风险管理报告中有详细论述）进行判定的。

此外，还应说明已采取的风险控制措施，例如符合协调标准、规定器械的有效使用期限、维护保养要求以及通过标签和说明书提供安全使用信息等，是如何致力于将这些风险降低到尽可能低的水平（AFARP）的。

临床评价在确认剩余风险可接受性中的作用

CEP需要清晰地阐明临床评价的一项核心作用（也是CEP所规划的主要活动之一）是收集和分析临床数据，用以进一步确认在器械带来预期受益并参照当前技术发展水平（SOTA）的前提下，那些已识别的剩余风险的可接受性。临床评价将特别关注与这些剩余风险相关的实际发生率、临床表现的严重程度，以及它们在真实世界临床应用中的具体影响。

评估临床风险的数据来源规划

为实现上述目标，CEP应概述在临床评价过程中计划收集和分析哪些类型的数据来评估和确认临床风险。这部分内容需要与临床评价的整体数据收集策略相呼应。可能的数据来源包括：

• 来自临床前研究的数据，特别是那些验证和确认器械设计符合相关安全标准（例如，协调标准等）的测试结果。
• 关于待评价器械或具有可比性的类似/等同器械的已发表文献中的临床数据。
• 来自待评价器械或类似/等同器械的上市后监测（PMS）数据，包括用户投诉、警戒系统报告、趋势报告等。
• 如果计划或正在进行临床研究，那么从中获得的临床数据也是评估风险的核心证据之一。

确保一致性与风险管理的动态更新

在整个产品生命周期中，风险管理文件、临床评价结果以及提供给用户的信息（如标签、使用说明书）之间保持持续一致性是非常重要的。CEP中应明确，在后续的临床评价报告（CER）中，将对这种一致性进行审查和确认。

风险管理本身是一个动态的、持续改进的过程。因此，CEP必须阐明这种互动机制：如果在临床评价过程中（包括文献回顾、PMS数据分析或临床研究），发现了任何先前未预见到的新危害，或者现有风险的严重性、发生率或可探测性被重新估计，或是对器械的受益风险平衡产生了新的疑问，这些信息都将及时反馈至风险管理流程。这将可能触发对风险评估文件的更新，必要时还将促使制造商制定并实施额外的风险控制措施。

与当前技术发展水平（SOTA）的关联

风险的可接受性判断往往需要参照当前公认的技术发展水平。因此，CEP中也应说明在评估风险时，会结合SOTA中关于同类器械可接受的风险水平和受益情况进行综合考量。

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In the Clinical Evaluation Plan (CEP), the primary purpose of the “Risk Management” chapter is not to re-execute risk management activities, but rather to clearly articulate how the risk management process and clinical evaluation activities interrelate and provide input to each other, collectively ensuring that the benefit-risk profile of the device under evaluation is acceptable for its intended use. This chapter should outline the identified clinical risks and detail how the clinical evaluation is planned to further confirm the controllability and acceptability of these risks.

When drafting this chapter, it is crucial to reflect the continuous, bi-directional interaction between risk management and clinical evaluation, a key requirement under the MDR.

Referencing the Existing Risk Management Framework

This chapter should explicitly state that the manufacturer has established and maintains a comprehensive risk management process in accordance with applicable standards (e.g., ISO 14971) and MDR requirements. The Clinical Evaluation Plan is developed within this established risk management framework. Therefore, it is necessary to outline how the risk management process has identified clinical risks associated with the device under evaluation. Typically, this information is derived from a series of core risk management documents, such as the Risk Management Plan, Hazard Analysis (HA, which may include Application HA, Design HA, etc.), Process/Manufacturing FMEA (PFMEA), and ultimately, the Risk Management Report. Referencing these documents in the CEP demonstrates that the risk context for the clinical evaluation is well-documented.

Identified Risks to be Addressed in Clinical Evaluation

After outlining the overall risk management framework, the CEP should briefly describe the significant clinical risks associated with the clinical use of the device under evaluation that have been identified through the aforementioned risk management activities. This includes the preliminary assessment of these risks (both initial risks and residual risks after mitigation by risk control measures) and how their acceptability has been determined against predefined criteria set forth in the Risk Management Plan (usually detailed in the Risk Management Report).

Furthermore, it should be explained how implemented risk control measures—such as conformity to harmonized standards, specification of the device’s useful lifetime, maintenance requirements, and provision of safety information through labeling and instructions for use—are intended to reduce these risks to a level as low as reasonably practicable (AFARP).

Role of Clinical Evaluation in Confirming Acceptability of Residual Risks

The CEP needs to clearly articulate that a core function of the clinical evaluation (and a primary activity planned within this CEP) is to collect and analyze clinical data. This data is used to further confirm the acceptability of the identified residual risks, considering the device’s claimed benefits and by reference to the current state-of-the-art (SOTA). The clinical evaluation will specifically focus on the actual occurrence rates, the severity of clinical manifestations, and the real-world clinical impact of these residual risks.

Planned Data Sources for Evaluating Clinical Risks

To achieve the above objective, the CEP should outline the types of data planned for collection and analysis during the clinical evaluation to assess and confirm clinical risks. This section needs to align with the overall data collection strategy of the clinical evaluation. Potential data sources include:

• Data from preclinical studies, particularly test results that verify and validate the device design’s conformity to relevant safety standards (e.g., harmonized standards).
• Clinical data from published literature on the device under evaluation (if any) or on comparable similar/equivalent devices.
• Post-Market Surveillance (PMS) data from the device under evaluation or similar/equivalent devices, including user complaints, vigilance system reports, trend reports, etc.
• If clinical investigations are planned or ongoing, the clinical data obtained from these will naturally be core evidence for risk assessment.

Ensuring Consistency and Dynamic Updates to Risk Management

It is important to emphasize the continuous maintenance of consistency throughout the product lifecycle between the risk management documentation, the information provided to users (e.g., labeling, Instructions for Use – IFU), and the findings of the clinical evaluation. The CEP should anticipate that this consistency will be reviewed and confirmed in the subsequent Clinical Evaluation Report (CER).

More critically, risk management itself is a dynamic, iterative process. Therefore, the CEP must articulate this interactive mechanism: if the clinical evaluation process (including literature reviews, PMS data analysis, or clinical investigations) uncovers any previously unforeseen new hazards, or if the severity, occurrence, or detectability of existing risks is re-estimated, or if new questions arise concerning the device’s benefit-risk balance, this information will be promptly fed back into the risk management process. This may trigger updates to risk assessment documents and, if necessary, prompt the manufacturer to develop and implement additional risk control measures.

Linkage to State-of-the-Art (SOTA)

The judgment of risk acceptability often needs to be made by reference to the currently accepted state-of-the-art. Therefore, the CEP should also mention that the assessment of risks will involve a comprehensive consideration of acceptable risk levels and benefits associated with similar devices, as documented in the SOTA.