临床开发计划(CDP)

在临床评价计划（CEP）中，“临床开发计划 (CDP)”章节扮演着规划蓝图的角色，它清晰勾勒出制造商为证明待评价医疗器械符合相关通用安全和性能要求（GSPR），并确认其在整个生命周期内的受益风险比所规划的一系列临床证据收集与评估活动。本章节应呈现一个从现有数据评估到必要的临床研究（如有必要），再到上市后临床跟踪（PMCF）的逻辑清晰、分阶段实施的策略。其详略程度应与器械的风险等级、创新程度、现有数据的充分性以及相关法规要求（如MDR附件XIV A部分1(a)）相匹配。

本部分内容应体现制造商对临床证据收集的前瞻性规划和承诺。

明确临床开发的当前阶段与总体策略

首先，CDP应简明扼要地阐述待评价器械当前的临床开发阶段。例如，是全新设计的器械寻求初次CE认证，还是对已上市器械的重大改型，或是基于成熟技术的迭代产品。这一背景信息直接影响后续临床证据收集策略的制定。

在此基础上，应概述获取和/或产生临床证据的总体策略。这包括说明计划如何利用现有数据，以及在现有数据不足以充分证明安全性和性能时，将如何通过新的临床研究来弥补差距。

现有临床相关数据的整合与利用计划

CDP应详细说明计划如何系统地收集、整合和评估已有的临床相关数据。这些数据来源可能包括：

• 临床前研究数据： 这是证明器械符合其技术规格和基本安全性能要求的基础。应概述已完成的关键临床前研究（如台架测试、模拟使用、动物实验等）及其主要结论如何支持临床安全性和性能的初步评估。
• 现有已发表文献数据： 说明计划如何对与待评价器械本身（如果存在相关文献）、或具有相似技术特性和预期用途的同类或等同器械相关的科学文献进行系统性检索、筛选和评价。
• 来自等同器械的数据（如适用）： 若在CEP的前续章节中已成功论证了与一个或多个等同器械的等同性，CDP应重申并细化计划如何利用这些等同器械的临床数据（包括已发表文献、上市后数据等）来支持待评价器械的临床评价。

上市前新临床研究的规划（如适用）

若通过对现有数据的全面评估后，发现尚不足以完全覆盖所有临床宣称、解决所有已识别的临床风险，或充分证明器械符合所有相关的GSPR，则CDP必须清晰阐述任何计划在上市前开展的新临床研究。

对于每一项计划中的上市前临床研究，CEP中的CDP部分应提供一个概要性描述（更详细的内容通常包含在专门的临床研究方案（CIP）和研究者手册（IB）中），至少应涵盖：

• 研究的基本原理和目标： 清晰说明该研究旨在解决哪些具体问题，或验证哪些特定的安全性和/或性能宣称。
• 研究设计概览： 例如，是探索性研究、可行性研究、关键性（pivotal）研究，还是注册登记研究等。
• 主要终点指标： 概述与器械安全性和性能宣称直接相关的、计划在研究中进行评估的主要临床结果。
• 目标受试人群和样本量考量： 简要说明研究拟纳入的受试者特征及大致的样本规模估算依据。
• 预期的时间节点与里程碑： 给出研究计划的主要时间安排。
• 合规性声明： 确认研究将遵循适用的法规要求（如MDR）、伦理原则以及相关标准（如ISO 14155）。

如果经过评估，现有数据被认为足以支持上市前的临床评价，无需新的上市前临床研究，CDP则必须提供充分且有力的论证来支持这一结论。

上市后临床跟踪 (PMCF) 的前瞻性规划

CDP不能仅局限于上市前的活动，它必须展现一个覆盖器械整个生命周期的临床数据收集情况，其中上市后临床跟踪（PMCF）是不可或缺的一环。PMCF旨在持续确认器械的临床安全性和性能，并在真实世界使用中监测其长期表现。

在CEP的CDP章节中，应概述PMCF的初步规划和策略方向。并且应当与器械的风险、特性以及在上市前临床评价时尚存的任何不确定性相适应。可以提及计划采用的PMCF活动类型，例如：

• 对常规上市后监测（PMS）数据的持续分析（包括用户投诉、警戒报告、使用趋势分析等）。
• 定期的系统性文献追踪和回顾。
• 通过用户反馈调查、患者报告结局（PROs） 等方式收集信息。
• 建立或参与产品注册登记研究。
• 开展特定的PMCF研究（例如，观察性研究、扩展队列研究，甚至是上市后对照研究，以解决特定的长期安全性和性能问题，或进一步验证在不同亚组人群中的表现）。

CDP中应阐明PMCF活动的主要目的，通常包括：

• 持续确认器械在其预期使用寿命内的临床安全性和性能表现。
• 识别和分析任何先前未知的潜在风险、副作用或并发症。
• 监测与该器械相关的当前技术发展水平（SOTA）的演变。
• 持续确认器械的受益风险比是否保持在可接受的范围内。

CDP与临床评价总体目标的关联

整个CDP的叙述应清晰地将其各项计划活动（无论是上市前还是上市后）与临床评价的根本目标紧密联系起来。即，这些活动是如何共同作用，以收集充分的临床证据来证明器械符合相关的GSPR、确认其受益风险判定，并科学地支持其各项临床宣称。同时，CDP的执行结果也将为风险管理过程的持续更新和临床评价报告的定期更新提供关键输入。

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Within the Clinical Evaluation Plan (CEP), the “Clinical Development Plan (CDP)” chapter serves as a strategic blueprint, clearly outlining the series of activities planned by the manufacturer to gather and evaluate clinical evidence. This evidence is necessary to demonstrate the conformity of the device under evaluation with the relevant General Safety and Performance Requirements (GSPRs) and to confirm its benefit-risk profile throughout its entire lifecycle. This chapter should present a logically sequenced and phased strategy, progressing from the assessment of existing data, through any necessary new clinical investigations (if required), to post-market clinical follow-up (PMCF). The level of detail should be proportionate to the device’s risk class, novelty, the adequacy of existing knowledge, and relevant regulatory requirements (such as MDR Annex XIV Part A, section 1(a)).

This chapter is essential to demonstrate the manufacturer’s proactive planning and commitment to generating clinical evidence.

Defining the Current Stage and Overall Strategy of Clinical Development

Firstly, the CDP should concisely state the current stage of the device’s clinical development. For instance, it might be a newly designed device seeking initial CE marking, a significant modification of an existing marketed device, or an iteration of a product based on well-established technology. This contextual information directly influences the subsequent strategy for clinical evidence generation.

Building on this, an overview of the general strategy for obtaining and/or generating clinical evidence should be provided. This includes specifying how existing data is planned to be leveraged and, if existing data is insufficient to fully demonstrate safety and performance, how new clinical investigations will be conducted to address these gaps.

Plan for Integration and Utilization of Existing Clinical-Relevant Data

The CDP should detail the plan for systematically collecting, integrating, and evaluating existing clinical-relevant data. These data sources may include:

• Preclinical Study Data: This forms the basis for demonstrating the device’s conformity with its technical specifications and fundamental safety and performance requirements. An overview of key completed preclinical studies (e.g., bench testing, simulated use, animal studies) and how their main conclusions support the initial assessment of clinical safety and performance should be provided.
• Existing Published Literature Data: It should describe the plan for systematically searching, screening, and appraising scientific literature relevant to the device under evaluation itself (if such literature exists), or to similar or equivalent devices with comparable technological characteristics and intended uses.
• Data from Equivalent Devices (if applicable): If equivalence to one or more equivalent devices has been successfully demonstrated in preceding chapters of the CEP, the CDP should reiterate and elaborate on the plan to utilize clinical data from these equivalent devices (including published literature, post-market data, etc.) to support the clinical evaluation of the device under evaluation.

Planning for New Pre-Market Clinical Investigations (if applicable)

If, after a comprehensive assessment of existing data, it is determined that this data is insufficient to fully cover all clinical claims, address all identified clinical risks, or adequately demonstrate conformity with all relevant GSPRs, then the CDP must clearly articulate any new pre-market clinical investigations planned.

For each planned pre-market clinical investigation, the CDP section of the CEP should provide a summary description (more detailed information is typically contained in dedicated Clinical Investigation Plans (CIPs) and Investigator’s Brochures (IBs)), covering at least:

• Rationale and Objectives of the Investigation: Clearly state the specific questions the investigation aims to answer or the specific safety and/or performance claims it intends to validate.
• Overview of Investigation Design: For example, whether it is an exploratory, feasibility, pivotal, or registry study.
• Primary Endpoints: Outline the main clinical outcomes directly related to the device’s safety and performance claims that are planned for assessment in the investigation.
• Target Population and Sample Size Considerations: Briefly describe the characteristics of the subjects to be enrolled and the basis for estimating the approximate sample size.
• Anticipated Timelines and Milestones: Provide a general schedule for the main phases of the investigation.
• Statement of Compliance: Confirm that the investigation will adhere to applicable regulatory requirements (e.g., MDR), ethical principles, and relevant standards (e.g., ISO 14155).

If, after evaluation, existing data is deemed sufficient to support the pre-market clinical evaluation without the need for new pre-market clinical investigations, the CDP must provide a robust and well-supported justification for this conclusion.

Proactive Planning for Post-Market Clinical Follow-up (PMCF)

The CDP must not be limited to pre-market activities; it must demonstrate a vision for clinical data collection that spans the entire lifecycle of the device, in which Post-Market Clinical Follow-up (PMCF) is an indispensable component. PMCF aims to continuously confirm the device’s clinical safety and performance and to monitor its long-term behavior in real-world use.

In the CDP chapter of the CEP, an outline of the initial PMCF plan and strategic direction should be provided. This should be proportionate to the device’s risks, characteristics, and any uncertainties remaining from the pre-market clinical evaluation. Types of planned PMCF activities that can be mentioned include:

• Continuous analysis of routine Post-Market Surveillance (PMS) data (including user complaints, vigilance reports, trend analysis).
• Regular systematic literature reviews and monitoring.
• Information gathering through user feedback surveys, Patient-Reported Outcomes (PROs), etc.
• Establishment of or participation in product registries.
• Conducting specific PMCF studies (e.g., observational studies, extended cohort studies, or even post-market controlled studies to address specific long-term safety and performance questions, or to further validate performance in different subgroups).

The CDP should articulate the main objectives of PMCF activities, which typically include:

• Continuously confirming the clinical safety and performance of the device throughout its expected lifetime.
• Identifying and analyzing any previously unknown potential risks, side-effects, or complications.
• Monitoring developments in the state-of-the-art (SOTA) relevant to the device.
• Continuously confirming that the device’s benefit-risk profile remains acceptable.

Linking the CDP to Overall Clinical Evaluation Goals

The entire narrative of the CDP should clearly connect its various planned activities (both pre-market and post-market) to the fundamental goals of the clinical evaluation. That is, how these activities collectively contribute to gathering sufficient clinical evidence to demonstrate conformity with relevant GSPRs, confirm the benefit-risk determination, and scientifically substantiate its clinical claims. Furthermore, the outcomes of the CDP activities will provide crucial input for the ongoing updates of the risk management process and the periodic updates of the Clinical Evaluation Report.