Clinical evaluation is a systematic process used to appraise and analyze clinical data related to a medical device. It compiles all available clinical evidence available to demonstrate compliance with regulatory requirements. The framework for conducting a clinical evaluation is outlined in Annex XIV, Part A of the European Medical Device Regulation (EU MDR) 2017/745.
This process is ongoing throughout the device’s lifecycle, starting during the development stage. Early clinical evaluations help identify gaps in data, determine the need for clinical investigations and generate safety and performance data. Clinical evaluation is mandatory for initial CE-marking, as part of the conformity assessment, and requires regular updates post-approval.
Manufacturers of all device classes (I, IIa, IIb, III) must perform clinical evaluations, documented in the Clinical Evaluation Plan (CEP) and Clinical Evaluation Report (CER). These documents are integral to the technical file and demonstrate compliance with General Safety and Performance Requirements (GSPRs) and an acceptable benefit-risk profile.
Clinical Evaluation Plan and Report
The preparation of the CEP and CER should be undertaken by a qualified person or team. Usually, they are prepared by a Regulatory Medical Writer, with input from different departments, such as regulatory and clinical affairs, risk management, and marketing. Ideally, these documents are reviewed by a medical expert in the relevant field.
Clinical Evaluation Plan (CEP)
The CEP provides the scope and the methodology, serving as a roadmap for gathering and analyzing clinical data.
Key elements of the CEP include:
- Scope: whether for initial CE-marking, updates, or modifications to a device.
- Identification of the relevant general safety and performance requirements (GSPRs).
- Full description of the device under evaluation, which should be aligned with the instructions for use and the technical documentation (intended purpose, target population, indications, contra-indications, clinical benefits, lifetime, etc.).
- If equivalence is claimed, the CEP should identify the equivalent device, providing scientific justification of the equivalence.
- A summary of the risk management plan, with the risk management strategy.
- Methodology for conducting the systematic literature review (which is also provided in a separate literature review plan), including keywords, search terms, databases selected, selection process, and appraisal plan.
- The clinical development plan of the device under evaluation, with a list of the studies conducted (first-in-human, pilot and pivotal studies, post-market clinical follow-up PMCF studies).
- The plan for the collection of non-clinical data, describing which type of non-clinical data will be collected (verification and validation testing, animal testing, etc.).
- Overview of the clinical data, with summaries of the clinical investigation plans.
- A summary of the planned PMS activities and methodology for the PMCF studies.
- Plan for the appraisal of the clinical data gathered from the different sources (literature on the device under evaluation, clinical investigations, PMS, PMCF, user feedback, etc.).
- Frequency of clinical evaluation update, which should be at least annual for class III or not yet well-established devices, and every 2 to 5 years for lower risk and well-established devices. Any new information or new risk identified during PMS should also trigger an update.
Clinical Evaluation Report (CER)
The CER documents the results of the clinical evaluation process, compiling all clinical and non-clinical data of the device under evaluation. Its purpose is to demonstrate that the device meets regulatory requirements and maintains an acceptable benefit-risk profile.
Key components of the CER include:
- Scope and GSPRs: aligned with the CEP.
- Full description of the device(s) under evaluation, which should be aligned with the CEP, the instructions for use and the technical documentation (intended purpose, target population, indications, contra-indications, clinical benefits, lifetime, etc.).
- If equivalence is claimed, the CER should identify the equivalent device, providing scientific justification of the equivalence, and use the equivalence table presented in MDCG 2020-5 (see section below on Equivalence).
- A summary of the risk management report, with the residual risks.
- Results of the systematic literature review, with the state of the art and the analysis of safety and performance data retrieved from the literature.
- Results of the non-clinical data testing.
- Clinical data gathered on the device under evaluation or the equivalent device.
- Clinical data generated through PMS and PMCF studies.
- Result of the appraisal of all data presented in the CER (literature on the device under evaluation, clinical investigations, PMS, PMCF, user feedback, etc.).
- Compliance with GSPRs: comparing safety and performance data from the device under evaluation obtained from the different sources with the state of the art.
- Benefit-risk assessment for each indication, considering magnitude and duration of benefits and risks, and comparing to the state-of-the art.
- Frequency of clinical evaluation update, as described in the CEP.
Stages of a clinical evaluation
The MEDDEV 2.7/1 revision 4 provides a 5-stage framework for conducting clinical evaluations, providing a clear and structured approach to ensure compliance.
Stage 0 – Defining the scope and preparing the CEP
The CEP is the foundation of the clinical evaluation process, detailing its objectives and methodology. The content of the CEP varies depending on the development stage of the device.
For non-CE-marked devices, the CEP focuses on the collection of foundational data.
For CE marked devices, the scope of the CEP may be broader and may include additional elements, such as:
- Changes to the devices, such as updates to design, manufacturing processes or instructions for use (IFU)
- Newly available clinical data
- Changes to the state of the art
- Identification of new risks and mitigation measures
- Findings from post-market surveillance (PMS).
Stage 1 – Identification of pertinent data
The clinical evaluation should encompass all relevant data related to the device under evaluation. This includes pre-clinical studies, pre- and post-market clinical investigations, as well as complaints, incident reports, and other findings from PMS. A systematic literature review is also conducted to ensure all available data are considered.
Data from similar devices can be included to provide valuable insights, such as identifying potential hazards and risks, design features causing performance or safety concerns, defining the state of the art, or establishing outcome parameters for the clinical benefits.
Importantly, all clinical data – whether favorable or unfavorable – must be included to present a complete picture of the device’s clinical profile.
Stage 2 – Appraisal of data
All data presented in the clinical evaluation should be appraised, to evaluate their relevance and importance in assessing the device’s safety and performance. The appraisal criteria are described in the CEP and enable the assignment of weight to each data set. Factors such as the quality of the study, including its design and methodology, and its relevance to the clinical evaluation are considered during this process.
A consistent and validated appraisal approach, such as the method detailed in the IMDRF MDCE WG/N56FINAL:2019 guidance document ensures reliability in assessing the data. The results of this appraisal are documented in the CER.
Stage 3 - Analysis of data
The analysis phase involves examining the collected data to demonstrate compliance to the GSPRs. This analysis can be qualitative or quantitative and is aimed at confirming the device’s intended performance and compliance with safety standards. During this stage, safety, and performance data from the device under evaluation are compared to the state of the art to ensure the device meets or exceeds established benchmarks.
The analysis also verifies that identified risks are adequately addressed in the IFU. A critical aspect of this stage is establishing the benefit-risk profile by comparing the device’s clinical benefits and risks with those of similar devices currently available. The resulting benefit-risk profile must be acceptable, and ideally, show that the device offers comparable or superior benefits to similar devices.
Stage 4 – Finalizing the CER
The final stage involves consolidating all findings into the CER. This document presents a comprehensive summary of all the data obtained from various sources, including literature, clinical investigations, PMS, and user feedback. The CER provides a detailed appraisal and analysis of the data, supporting the intended purpose, clinical performance, and claims of the device. It demonstrates that the benefit-risk profile of the device is acceptable and confirms the usability of the device in its intended context.
The CER must address all models and sizes of the device, ensuring that any identified gaps are clearly acknowledged. It should also align with the CEP, the device’s risk management documentation, the IFU, and the broader technical documentation.
Equivalence
The requirements to show equivalence have become significantly stricter under the MDR. Guidance on these requirements is provided in MDCG 2020-5. Manufacturers must include clinical data on the equivalent device in the clinical evaluation, and demonstrate equivalence in terms of technical, biological, and clinical characteristics. Any differences between the two devices should not impact safety or performance.
As part of the clinical evaluation, manufacturers must justify the level of clinical evidence required to demonstrate conformity with the relevant GSPRs.
Data from the equivalent device undergo the same process as the device under evaluation, including identification, appraisal, analysis and are presented in the CER.
To support equivalence, the equivalence table provided in the MDCG 2020-5 can be a valuable tool. This table helps manufacturers systematically align data from both devices, highlight differences, and ensure any variations are clinically insignificant. A scientific justification must be provided to confirm that there are no meaningful differences in safety or performance between the two devices.
Clinical evaluation for legacy devices
Legacy devices, which obtained CE-marking under the Medical Device Directive (MDD), typically have pre-market data, supplemented by PMS data. However, some legacy devices may require additional clinical evidence to meet the stricter MDR requirements.
The MDCG 2020-6 guidance outlines strategies for conducting clinical evaluations for legacy devices. Manufacturers should perform a gap analysis to identify areas where additional clinical evidence is needed to comply with MDR standards. All available post-market data should be included in this evaluation, such as PMS, and PMCF data, complaints, incident reports, device registries, and relevant literature.
If existing clinical evidence is insufficient, additional PMCF studies must be conducted. This may include clinical investigations, systematic literature reviews, or well-designed, high-quality questionnaires. Such studies should have clear research questions, objectives and endpoints, with robust design and analysis methods to ensure reliability.
When clinical evidence is still inadequate to fully support all claims made by the manufacturer, the device’s intended purpose should be narrowed down to align with the available evidence.
By following these approaches, manufacturers can ensure that their clinical evaluations are robust, systematic, and compliant with MDR requirements, ultimately contributing to safer and more effective medical devices.
Relevant guidance on clinical evaluations
- European Medical Device Regulations (EU MDR) 2017/745
- MEDDEV 2.7/1 revision 4 Clinical Evaluation: A Guide for Manufacturers and Notified Bodies under Directives 93/42/EEC or 90/385/EEC
- MDCG 2020-5 Clinical Evaluation – Equivalence
- MDCG 2020-6 Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC
- MDCG 2020-1 Guidance on Clinical Evaluation (MDR)/Performance Evaluation (IVDR) of Medical Device Software
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