MDCG 2020-3 Rev. 1: Updates to MDR Signifcant Changes Guidance
May 16, 2023
EU, Swiss, UK Guide: Systems/Procedure Packs and Kits
June 9, 2023Page Last Reviewed: 22 April 2024
A critical part of the clinical evaluation is the Clinical Evaluation Plan (CEP). It establishes the scope of the clinical evaluation and sets up a guide for the entire clinical evaluation process. The clinical evaluation plan defines how the clinical evaluation is created, updated, and how much clinical data is needed to appropriately assess the risk-benefit profile of your medical device.
Clinical Evaluation Plan: Overview
Clinical evaluations are systematic processes put in place to continuously generate, collect, analyze, and assess the clinical data available for a medical device. This is to verify its continued safety and performance.
The MDR states that manufacturers must continuously conduct and document a clinical evaluation and to do so, a clinical evaluation plan must be established.
This clinical evaluation plan must include at least:
- Identification of the general safety and performance requirements (GSPRs) that require support from relevant clinical data
- The device’s intended purpose
- A specification of the intended target groups, including clear indications and contra-indications
- A detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters
- A specification of methods to be used for examining the qualitative and quantitative aspects of clinical safety, with clear reference to residual risks and side effects
- An indicative list and specification of parameters to be used to determine the acceptability of the risk-benefit profile of the medical device, for all the indications and intended purposes of the device
- An indication of how risk-benefit issues are to be addressed
- A clinical development plan indicating the progression from exploratory investigations to confirmatory investigations
These requirements, however, are the bare minimum of what should be included in a clinical evaluation plan.
Clinical Evaluation Plan: Structure
The clinical evaluation, and by extension the clinical evaluation plan, should be tailored to the risk classification of the device. However, the clinical evaluation plan should follow a general structure that can be used as a reference point.
A suggested structure could be:
- Clinical evaluation scope and objectives
- Device description including device models and sizes, device group, device images, and anything else that can help the notified body make sense of and properly identify the device and accessories
- Intended purpose and medical indications, target population, indications, contraindications, and any warnings or similar included in the IFU and labeling
- Device change history
- Equivalence information if equivalence is claimed, or information on similar devices
- State-of-the-art information, including a background in the medical field and a discussion of alternative treatments or therapies
- Safety and performance claims made by the manufacturer in their instructions for use and/or marketing materials
- Clinical benefits with a justification of the clinical outcome parameters
- Identification of the general safety and performance requirements that needs to be supported by the clinical data
- Risk documentation information such as clinical risks, residual risks, side effects, and hazard identification
- Methodology for evaluating the clinical safety and determining the residual risks and side effects
- Safety and performance parameters to determine the acceptability of the risk-benefit profile when the device is used as intended, per state-of-the-art
- Clinical development plan
- Data sources and types of data to be used in the clinical evaluation, such as clinical investigations, post-market surveillance, scientific literature, pre-clinical studies, regulatory databases, etc.
- Detailed literature search protocol for identifying, appraising, and analyzing clinical data
Clinical Evaluation Plan: Key Considerations
Change History
The Clinical Evaluation Plan should include a description of relevant changes made to the device that impact the risk-benefit profile of the device.
Many changes are not clinically relevant, such as administrative changes to the labeling, and need not be considered. However, any change that clinically impacts the assessment of the device should be described.
These changes include:
- Design changes
- Changes to materials or manufacturing process
- Changes to the claims in information materials provided by the manufacturer, such as instructions for use, labeling, marketing materials, etc.
- Changes to the target or equivalence device that impact the equivalence claim (if applicable)
These changes should be listed in the clinical evaluation plan. Further, a discussion on their impact on the risk-benefit profile and clinical indications of the device should be included and taken into consideration.
Equivalence
Most medical devices will not be able to claim equivalence for their clinical evaluation. Equivalence claims need to be substantiated with significant data from the equivalent device. Most manufacturers will not have access to this data unless they are the manufacturer of both devices.
Equivalence justifications require:
- Descriptions of the clinical, biological, and technical characteristics that affect clinical properties of the devices,
- Identification of pre-clinical studies carried out and literature used,
- Summaries and evaluations of the methodological qualities of the studies, and
- Assessments of the scientific validity of the information.
You must evaluate comparative tabulations for your device versus the equivalent device. It should show the parameters relevant to the evaluation of the clinical, biological, and technical characteristics. Additionally, comparative drawings and pictures of both devices should be provided.
Generally, using similar devices for literature search and clinical evaluation is recommended over equivalence. This is unless there is full availability of the technical file and any clinical data of the equivalent device. For more information on equivalence, please refer to the EU guidance document MDCG 2020-5.
Identification of clinical data
Some lower-risk devices might depend almost entirely on scientific literature and post-market surveillance information for their clinical data. However, there are many sources of clinical data that should be investigated.
Clinical data generated by the manufacturer typically includes:
- Pre-market clinical investigations
- Clinical data from risk management activities
- Clinical data from post-market surveillance activities in Europe and other markets, including:
- Post-market Clinical Follow-up (PMCF) studies
- Post-market surveillance and vigilance reports
- Literature searches and evaluations made for post-market surveillance
- Incident reports and complaints, including the manufacturers’ own evaluations and reports
- Field safety corrective actions (FSCAs)
- Different use cases, such as custom-made devices, compassionate use or humanitarian exemption programs, explanted devices, etc.
- Pre-clinical studies, such as bench test reports including verification and validation data
Clinical data retrieved from literature (scientific journals, books, gray literature, theses, regulatory databases, implant registries, clinical trials, etc.) are used to complement the data generated by the manufacturer. It helps establish any clinical data relevant to the target, or similar, devices and current knowledge/state-of-the-art.
Literature Search Protocol
The clinical evaluation plan should include an objective, non-biased, systematic literature search protocol. Literature reviews are one of the most critical parts of the clinical evaluation and it is important to get it right.
The literature search protocol identifies and addresses the objectives of the literature review by:
- Specifying the literature review questions, and
- The methodology of the search and review.
The methodology needs to explain how the scientific literature is identified, selected, collected, and appraised. The PICO (Patient characteristics, type of Intervention, Control, and Outcome) method is a common search and review method. The literature review should be objective and justified. This means it must include all data about the target and similar devices, whether that data is favorable or non-favorable. The selected literature should always reflect the intended use of the device.
Regulatory Databases
When screening for literature to support the safety and performance claims of the device, most manufacturers are focused on scientific publications found in online journals, e.g., PubMed and Embase. However, an equally important place to look for clinical evidence is regulatory and vigilance databases, such as the FDA MAUDE or the UK MHRA Medical Alert databases.
In these databases, you can find adverse event reports and recalls concerning your target and similar devices. Reported adverse events can provide a lot of clinical data regarding the real-life safety and performance of your device when used by patients, health professionals, and other users.
To appropriately establish a search protocol for regulatory databases, you must have a basic understanding of how each database works. Search terms used in FDA MAUDE will not necessarily give good results in the UK MHRA or Brazilian ANVISA Events databases, as they have different underlying search algorithms. Your search protocol should clarify the search terms and methodology used for each database and describe how each database is approached.
Templates, Workflows, and Diagrams
Including diagrams can immensely help the competent authority/notified body gain a deeper understanding of the literature search workflow. It also demonstrates that you have a clear understanding of the processes used during data collection and analysis.
Likewise, it can be useful to include templates of your literature search outputs, appraisal methodology, and workflows.
We recommend including templates for each step of your clinical evaluation that involves data, for example, as appendices. Including the templates from the very beginning of your clinical evaluation process ensures clear and systematic reporting of your results and outputs. It can convey to the competent authority/notified body that you have strong processes in place for every step of your clinical evaluation. You should also include all your appraisal and data weighting information in the clinical evaluation plan.
Next Step: Writing the Clinical Evaluation Report
For more information, please read: Clinical Evaluation Reports – General Structure and What to Include
