临床评价范围

在临床评价计划（CEP）中，“临床评价范围”的核心任务是精确界定本次临床评价工作的边界、深度和焦点。一个清晰、周全的范围定义，能确保临床评价活动既全面覆盖所有法规要求和关键临床问题，又避免漫无目的地偏离核心目标，从而高效、准确地评估待评价医疗器械的安全性和性能。

本章节的内容旨在向所有相关方（包括内部团队、公告机构等）清晰传达评价将涵盖哪些内容、基于何种考量，以及将如何进行。

明确待评价器械及其核心背景

临床评价范围的界定，首先始于对核心评价对象的清晰识别。需要明确指出本次临床评价所针对的具体医疗器械名称，以及所覆盖的型号、规格或系列（如果适用）。

应阐明该器械当前的生命周期阶段。例如，是正在寻求初次CE认证的全新器械，还是对已上市器械的重大变更进行评估，或是对一个成熟的“遗留器械”按照MDR要求进行的再评价。不同的生命周期阶段，其评价的侧重点和所需证据的深度自然有所不同。

此外，若待评价器械包含任何需要特别关注的设计特征（例如，采用了创新材料、包含药物成分、动物或人体源性材料等）、特定的预期用途或适应症（例如，针对特定罕见病、或在特定高风险操作中使用），或面向特殊的目标患者人群（如儿童、孕妇、或免疫功能低下者），这些都必须在范围中明确，它们往往需要更具针对性的数据收集和风险评估策略。

阐明评价目标与核心宣称

评价范围的设定必须紧密围绕待评价器械的预期用途和制造商所提出的各项临床宣称。应清晰列出或概述这些关于器械安全性、临床性能、以及预期临床受益的关键宣称。

同时，范围部分应明确本次临床评价旨在证明器械符合哪些相关的通用安全和性能要求（GSPR），尤其是GSPR 1（关于器械达到预期目的且安全有效）和GSPR 8（关于临床评价的要求），以及其他与该器械类型和特性相关的GSPR条款。

界定数据来源的依赖程度与策略

临床评价范围需要清晰规划将依赖哪些数据来源，以及如何利用这些数据。

• 等同性路径的考量（如适用）： 如果计划通过与一个或多个已上市器械的“等同性”路径来进行临床评价，则本范围章节应再次确认这一策略。需要简要重申将哪些器械作为等同器械，并明确指出，对这一等同性主张的持续适宜性进行评估本身，也属于本次临床评价的范围之内。同时，应确认是否有足够的高质量临床数据可从这些等同器械获取，用以支持待评价器械的临床宣称。
• 当前技术发展水平（SOTA）的应用： 必须明确界定将如何确定和应用当前的技术发展水平（SOTA）作为评价的参照基准。这包括识别相关的临床状况及其自然病程、现有的标准治疗方法（涵盖其他标杆器械、替代治疗技术等），以及所有适用的国际/协调标准和行业指南文件。临床评价的一个重要方面就是将待评价器械的安全性和性能置于此SOTA背景下进行比较和衡量。
• 与风险管理的整合： 评价范围需明确阐述临床评价将如何系统地处理在风险管理过程中已识别的各项临床风险。核心在于通过临床数据来确认，在综合考量器械的预期受益和当前SOTA后，所有剩余风险是否均处于可接受的水平。此外，临床评价还致力于通过收集的临床证据来验证已知风险的实际发生率，或识别出先前未被发现的潜在新风险。
• 计划使用的数据类型与来源： 应概述在临床评价过程中，计划搜寻、筛选和纳入分析的具体数据类型。通常包括：
  • 临床前数据： 例如，制造商内部完成的台架测试、动物实验、生物相容性评估等，用以支持器械的基本安全、性能和对相关标准的符合性。
  • 已发表的科学文献： 关于待评价器械本身（若有）或类似/等同器械的临床研究、病例报告、系统综述等。
  • 临床研究数据： 若有正在进行或已完成的针对待评价器械的临床研究，其数据是核心证据。
  • 上市后监测（PMS）数据： 包括用户投诉、不良事件报告、警戒数据、文献监测、用户反馈等。
  • 不良事件数据库信息： 从各国监管机构或专业数据库中获取的与同类器械相关的不良事件报告。

应对变更与新出现的临床考量

临床评价范围的设定还需具备前瞻性和适应性。

• 如果待评价器械在其设计、制造工艺、预期用途、标签或使用说明等方面，较之先前版本（如有）或在开发过程中发生了任何相关变更，评价范围必须包含对这些变更可能带来的临床影响进行评估。对于全新器械，则重点在于其创新特性所带来的特定评估需求。
• 评价范围还应覆盖一个持续的过程，即主动识别和评估任何与该器械、其同类产品或相关技术相关的新出现的临床安全或性能问题。这些信息可能来源于最新的科学文献、监管机构的警示、专业学会的意见，或通过PMS活动获得。

与上市后监测（PMS）活动的衔接

临床评价并非一次性活动，其结果与上市后监测（PMS）及上市后临床跟踪（PMCF）紧密相连。因此，评价范围应考虑：

• 本次临床评价的结论将如何为正在进行的PMS活动（特别是PMCF计划的制定或调整）提供输入和指导。
• 未来的临床评价报告（CER）更新将如何系统地纳入新的PMS数据、PMCF结果以及SOTA的任何变化，以确保临床评价的持续有效性和及时性。

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Within the Clinical Evaluation Plan (CEP), the “Clinical Evaluation Scope” chapter is to precisely define the boundaries, depth, and focus of the current clinical evaluation activities. A clear and comprehensive scope definition ensures that the clinical evaluation comprehensively covers all regulatory requirements and key clinical questions, while also preventing it from becoming overly broad or deviating from its central objectives. This approach facilitates an efficient and accurate assessment of the safety and performance of the device under evaluation.

The drafting of this chapter should aim to clearly communicate to all relevant parties (including internal teams, Notified Bodies, etc.) what the evaluation will encompass, based on what considerations, and how it will be conducted.

Defining the Device Under Evaluation and Its Core Context

The definition of the clinical evaluation scope begins with a clear identification of the core subject of the evaluation. The specific name of the medical device targeted by this clinical evaluation, along with the models, sizes, or series it covers (if applicable), needs to be explicitly stated.

Subsequently, the device’s current lifecycle stage should be elucidated. For instance, whether it is a new device seeking initial CE marking, an evaluation of a significant change to a marketed device, or a re-evaluation of a mature “legacy device” according to MDR requirements. Different lifecycle stages naturally entail different emphases in the evaluation and varying depths of required evidence.

Furthermore, if the device under evaluation incorporates any design features requiring special attention (e.g., use of innovative materials, inclusion of medicinal substances, materials of animal or human origin), specific intended uses or indications (e.g., for a rare disease, or use in a specific high-risk procedure), or is intended for particular target patient populations (such as children, pregnant women, or immunocompromised individuals), these must be highlighted within the scope. Such aspects often necessitate more targeted data collection and risk assessment strategies.

Articulating Evaluation Objectives and Key Claims

The scope of the evaluation must be closely aligned with the intended use of the device under evaluation and the various clinical claims made by the manufacturer. These key claims regarding the device’s safety, clinical performance, and intended clinical benefits should be clearly listed or summarized.

Concurrently, the scope section should specify which relevant General Safety and Performance Requirements (GSPRs) this clinical evaluation aims to demonstrate conformity with, particularly GSPR 1 (regarding the device achieving its intended purpose and being safe and effective) and GSPR 8 (regarding clinical evaluation requirements), as well as other GSPRs relevant to the device type and characteristics.

Defining the Extent of Reliance on Data Sources and Strategy

The scope of the clinical evaluation needs to clearly map out which data sources will be relied upon and how this data will be utilized.

• Consideration of the Equivalence Pathway (if applicable): If the clinical evaluation plans to follow an “equivalence” pathway with one or more marketed devices, this scope section should reaffirm this strategy. It needs to briefly reiterate which device(s) are considered equivalent and explicitly state that assessing the continued appropriateness of this equivalence claim itself falls within the scope of this clinical evaluation. Additionally, it should confirm whether sufficient high-quality clinical data is available from these equivalent device(s) to support the clinical claims for the device under evaluation.
• Application of State-of-the-Art (SOTA): It must be clearly defined how the current state-of-the-art (SOTA) will be established and applied as a benchmark for the evaluation. This includes identifying relevant clinical conditions and their natural course, existing standard treatment modalities (covering other benchmark devices, alternative therapeutic technologies, etc.), and all applicable international/harmonized standards and industry guidance documents. A significant aspect of the clinical evaluation is to compare and measure the safety and performance of the device under evaluation against this SOTA backdrop.
• Integration with Risk Management: The scope needs to explicitly describe how the clinical evaluation will systematically address the various clinical risks identified during the risk management process. The core is to confirm, through clinical data, that all residual risks are at an acceptable level when considering the device’s intended benefits and the current SOTA. Furthermore, the clinical evaluation also aims to verify the actual incidence rates of known risks or to identify potential new risks not previously discovered, using the collected clinical evidence.
• Planned Data Types and Sources: An overview of the specific types of data planned for retrieval, screening, and inclusion in the analysis during the clinical evaluation should be provided. It includes:
  • Preclinical data: E.g., manufacturer’s internal bench testing, animal studies, biocompatibility assessments, supporting the device’s basic safety, performance, and conformity to relevant standards.
  • Published scientific literature: Clinical studies, case reports, systematic reviews, etc., concerning the device under evaluation itself (if available) or similar/equivalent devices.
  • Clinical investigation data: If clinical investigations are ongoing or have been completed for the device under evaluation, their data will naturally be core evidence.
  • Post-Market Surveillance (PMS) data: Including user complaints, adverse event reports, vigilance data, literature monitoring, user feedback, etc.
  • Adverse event database information: Adverse event reports related to similar types of devices obtained from national regulatory agency databases or specialized professional databases.

Addressing Changes and Newly Emerging Clinical Considerations

The definition of the clinical evaluation scope also needs to be forward-looking and adaptable.

• If the device under evaluation has undergone any relevant changes in its design, manufacturing process, intended use, labeling, or instructions for use compared to previous versions (if any) or during its development, the scope must include an assessment of the potential clinical impact of these changes. For a completely new device, the focus will be on the specific evaluation needs arising from its innovative features.
• The scope should also encompass an ongoing process to actively identify and evaluate any newly emerging clinical safety or performance concerns related to the device, its analogues, or associated technologies. This information may originate from the latest scientific literature, warnings from regulatory authorities, opinions from professional societies, or be captured through PMS activities.

Linkage with Post-Market Surveillance (PMS) Activities

Clinical evaluation is not a one-time event; its findings are closely linked with Post-Market Surveillance (PMS) and Post-Market Clinical Follow-up (PMCF). Therefore, the scope should consider:

• How the conclusions of this clinical evaluation will provide input and guidance for ongoing PMS activities (particularly the development or adjustment of the PMCF plan).
• How future Clinical Evaluation Report (CER) updates will systematically incorporate new PMS data, PMCF results, and any evolution in the SOTA to ensure the continued validity and timeliness of the clinical evaluation.