How to Prepare Your Clinical Evaluation Plan Template

In this article, we will delve into the intricacies of developing a robust Clinical Evaluation Plan using expert regulatory terminology, equipping you with the knowledge to navigate this essential aspect of your MedTech product development.

As the medical device industry evolves and regulatory requirements become more stringent, the need for a well-defined Clinical Evaluation Plan (CEP) has become paramount.

The CEP plays a crucial role in assessing the safety and performance of medical devices, ensuring their compliance with Annex XIV of the Regulation (EU) MDR 2017/745 (MDR), MDCG 2020-6, and MEDDEV 2.7.1. Rev.4.

1. Clinical evaluation of your medical device

The clinical evaluation of a medical device must be thorough and objective. Manufacturers should consider both favourable and unfavourable clinical data when developing the Clinical Evaluation Plan.

The depth and extent of the clinical evaluation must remain proportionate to the device. This includes its nature, risk class, intended purpose, manufacturer claims, and associated risks.

Manufacturers may base a clinical evaluation on clinical data from an equivalent device when they can demonstrate equivalence. The demonstration of equivalence must cover technical, biological, and clinical characteristics. Notified Bodies strongly recommend claiming equivalence against only one equivalent device.

Under MDR Article 61(1) and Annex XIV, manufacturers must plan, conduct, and document the clinical evaluation. The planning phase must be documented in a Clinical Evaluation Plan. The outcomes of the evaluation and the supporting clinical evidence must then be documented in a Clinical Evaluation Report.

2. What is a Clinical Evaluation Plan?

A Clinical Evaluation Plan (CEP) is a documented strategy that defines a systematic and planned approach to assess the safety and performance of a medical device throughout its lifecycle.

This clinical evaluation plan template provides the framework for collecting, appraising, and analyzing clinical data. Its purpose is to demonstrate conformity with the General Safety and Performance Requirements (GSPRs) set out in Annex I of the MDR.

3. Navigating Annex XIV of MDR 2017/745: Key Requirements

According to Part A, Section 1 of Annex XIV of the MDR, the manufacturer must establish and regularly update the Clinical Evaluation Plan. This ensures that the clinical evaluation remains planned, continuously performed, and properly documented.

Annex XIV defines the minimum requirements that every Clinical Evaluation Plan must address.

Minimum Requirements of a Clinical Evaluation Plan

The CEP must include:

A clinical development plan outlining the progression from exploratory investigations to confirmatory clinical investigations and PMCF activities, including milestones and acceptance criteria.
Identification of GSPRs that require support from relevant clinical data.
Specification of the intended purpose of the device.
Clear definition of target groups, including indications and contraindications.
Description of intended clinical benefits with defined clinical outcome parameters.
Methods for evaluating qualitative and quantitative aspects of clinical safety, including residual risks and side effects.
Parameters used to assess the acceptability of the benefit-risk ratio based on the current State of the Art.
An explanation of how benefit-risk issues related to specific components, such as medicinal substances or animal or human tissues, are addressed.

3.1. Clinical Data from Systematic Scientific Literature Reviews

Manufacturers should conduct a systematic scientific literature review to identify relevant clinical data for the device and its intended purpose.

The review should also identify gaps in the available clinical evidence. This supports a complete and transparent understanding of the existing data landscape.

Using structured methodologies such as PRISMA and PICO is recommended, as these approaches improve the systematic nature and reproducibility of the literature search.

3.2. Clinical Data from Clinical Investigations

Manufacturers should design and conduct clinical investigations in line with the Clinical Development Plan.

These investigations should generate new or additional clinical data when existing evidence does not sufficiently demonstrate safety and performance. The generated data should directly support the objectives of the Clinical Evaluation Plan.

3.3. Clinical Data Appraisal and Suitability

Manufacturers must appraise all relevant clinical data to determine their suitability for demonstrating device safety and performance.

This appraisal should consider data quality, reliability, and relevance. It should also follow the hierarchy of clinical evidence described in Appendix III of MDCG 2020-6 when assessing conformity with MDR GSPRs.

3.4. Clinical Data Analysis and Conclusions

Manufacturers must analyze all relevant clinical data, including literature data, existing clinical studies, and newly generated clinical investigation data.

The analysis should support clear conclusions on safety, clinical performance, and clinical benefits. This process includes data interpretation, statistical analysis, and benefit-risk assessment. The outcome must support robust, evidence-based conclusions within the Clinical Evaluation Plan.

4. Navigating MDCG 2020-6: Key Considerations for Your Clinical Evaluation Plan

The MDCG 2020-6 guidance, “Regulation (EU) 2017/745: Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC”, provides detailed direction on how to perform a clinical evaluation under the MDR. It supports both manufacturers and Notified Bodies in assessing clinical evidence for legacy medical devices.

This guidance is particularly relevant when preparing a clinical evaluation plan template that complies with MDR requirements.

4.1. Clinical Evaluation Plan Documentation Requirements

MDCG 2020-6 confirms that manufacturers must document a Clinical Evaluation Plan in accordance with MDR Annex XIV. The guidance also provides practical recommendations to support compliance with Annex XIV, Section 1(a).

A compliant Clinical Evaluation Plan should include:

Identification of the applicable General Safety and Performance Requirements (GSPRs).
A clear definition of the intended purpose, target patient groups, indications, and contraindications.
A detailed description of the intended clinical benefits, supported by defined clinical outcome parameters.
Specification of qualitative and quantitative aspects of clinical safety and clinical performance.

4.2. Sources of Clinical Data

According to MDCG 2020-6, the Clinical Evaluation Plan must clearly identify all relevant sources of clinical data. These sources may include pre-market, post-market, and newly generated clinical data.

Pre-market clinical data may consist of:

Clinical investigation reports for the device under evaluation.
Clinical investigations or studies published in scientific literature for equivalent devices.
Peer-reviewed literature reporting other clinical experience with the device or an equivalent device.
Additional pre-market data, such as case reports related to device use.

Post-market clinical data may include:

Post-Market Surveillance (PMS) clinical data.
Complaint handling and vigilance reports.
Post-Market Clinical Follow-up (PMCF) studies and investigations.
Independent clinical studies, device registries, and relevant literature data.

Newly generated clinical data should also be included when available and justified.

The Clinical Evaluation Plan must also describe the system used to appraise and analyze all clinical data sources.

4.3. Minimum Content of a Clinical Evaluation Plan for Legacy Devices

Appendix II of MDCG 2020-6 defines the minimum content required for a Clinical Evaluation Plan for legacy devices. This minimum content includes:

Identification of GSPRs that require support from clinical data.
Specification of the intended purpose of the device.
Clear definition of target groups, including indications and contraindications.
Description of intended clinical benefits with defined clinical outcome parameters.
A strategy to identify, analyze, and assess alternative treatment options.
Methods for evaluating qualitative and quantitative aspects of clinical safety, including residual risks and side effects.
Defined parameters to assess the acceptability of the benefit-risk ratio based on the current State of the Art.
An explanation of how benefit-risk issues related to specific components, such as medicinal substances or animal or human tissues, are addressed.
A strategy and methodology to identify, analyze, and appraise all relevant clinical data under the MDR definition of clinical data.
Evidence supporting equivalence when clinical data from an equivalent device is used.
A justification of the required level of clinical evidence based on device characteristics and intended purpose.
A strategy for the systematic collection, analysis, and assessment of post-market surveillance data to demonstrate continued safety and performance of legacy devices.

4.4. Hierarchy of Clinical Evidence Under MDCG 2020-6

Appendix III of MDCG 2020-6 introduces a hierarchy of clinical evidence to support conformity with MDR GSPRs. This hierarchy ranks different types of clinical data from strongest to weakest.

Manufacturers should consider this hierarchy when defining the appraisal methodology in their clinical evaluation plan template. Applying the suggested hierarchy supports a robust and transparent assessment of clinical evidence and strengthens the overall Clinical Evaluation Plan.

5. Navigating MEDDEV 2.7.1. Rev.4: What To Consider?

MEDDEV 2.7.1. Rev.4 refers to the fourth revised version of the Medical Device Vigilance Guidance Document.

This document encourages the adoption of a standardized approach to clinical evaluation for medical devices that fall under the regulation of directives 90/385/EEC and 93/42/EEC.

MEDDEV 2.7.1 Rev.4 continues to be used even after the implementation of MDR since it offers additional interpretive guidance and practical recommendations that complement the MDR requirements.

Section 7 of MEDDEV 2.7/1 rev. 4 addresses the definition of scope of the clinical evaluation, which constitutes the Stage 0 of a clinical evaluation, and, according to MDR and MDCG 2020-6, states that the manufacturer should set up a Clinical Evaluation Plan for the device under evaluation.

Recognizing the wide range of technologies employed in medical devices, along with their diverse histories and associated risks, is crucial.

Therefore, Section 7 of MEDDEV 2.7/1 rev. 4 also examines the different aspects to be considered for setting up a CEP depending on the stage in the lifecycle of the product and its regulatory status (i.e., before CE-marking, For CE-marked devices).

Moreover, Appendix A3 of MEDDEV 2.7/1 rev. 4 lists information that can be relevant for planning clinical evaluations. It is paramount that the manufacturer ensures that input for the Clinical Evaluation Plan shows alignment with the device’s “label, instructions for use, promotional or sales materials or statements” and with the device’s updated risk management documentation.

Must have considerations for your Clinical Evaluation Plan Template MDR-based

At MDx CRO, we recognize the significance of a well-structured Clinical Evaluation Plan (CEP) in ensuring the safety and performance of medical devices.

The design of a Clinical Evaluation Plan (CEP) template according to the Medical Device Regulation (MDR) 2017/745 should be tailored to the specific typology of the manufacturer’s device.

This customization is critical as every medical device has unique attributes, different indications for use, target populations, and risk profiles.

Therefore, the use of a generic template for all devices is not recommended. Although it might be tempting to use a “one-size-fits-all” approach for efficiency reasons, such practice could overlook the MDR’s specific requirements for each individual device, potentially leading to non-compliance with established safety and efficacy standards.

Additionally, lack of specificity could lead to erroneous or inappropriate conclusions in the clinical evaluation, jeopardizing the device’s approval for marketing. In summary, it is essential that each Clinical Evaluation Plan is designed and tailored specifically for the device being evaluated, in line with the guidelines of the MDR 2017/745.

Despite the unique considerations required for each device’s Clinical Evaluation Plan (CEP) under the MDR 2017/745, we understand the value of having a general framework to start from. Therefore, we will provide a template that serves as a starting point for the development of a Clinical Evaluation Plan.

This template will include essential elements required under the MDR 2017/745 such as:

Plan rationale
Device description
Clinical background
Identification of pertinent data sources
Clinical evaluation method
Plan for the appraisal of clinical data.

Remember, this is a guide to help initiate the process and not a final document. You will need to tailor the template to fit your specific device, its indications, target population, risk factors, and other device-specific attributes.

Our intention is to help streamline the process, providing structure while also emphasizing the importance of customization to meet the regulatory requirements.

Clinical Evaluation Plan Template Guidance

To streamline the development process and support compliance with regulatory requirements, this clinical evaluation plan template outlines the recommended structure and content of a Clinical Evaluation Plan (CEP). It helps manufacturers document clinical evidence in line with applicable regulations and guidance.

SECTION 1. SUMMARY
SECTION 2. REFERENCES
SECTION 3. ACRONYMS AND DEFINITIONS
SECTION 4. RESPONSIBILITIES
SECTION 5. SCOPE OF THE CLINICAL PLAN AS PART OF THE CLINICAL EVALUATION

This section defines the scope of the Clinical Evaluation Plan within the overall clinical evaluation process. It addresses the applicable General Safety and Performance Requirements (GSPR). It also references previous clinical evaluations and the current CEP.

The section explains any deviations from the CEP and justifies them when needed. In addition, it covers the Instructions for Use (IFU), device labeling, and related risk management activities.

SECTION 6. DEVICE DESCRIPTION

This section provides a clear and structured description of the medical device. It includes the device name, classification, and a brief technical overview. It also lists device components, materials, sizes, and available models.

The manufacturer name, generic device group, and device lifecycle stage must be stated. The section also explains the intended purpose of the device and how it achieves that purpose.

In addition, it defines the clinical condition, target patient population, and target user group. Contraindications, warnings, cautions, precautions, and known undesirable effects are documented to support the clinical evaluation.

SECTION 7. CLINICAL BACKGROUND AND STATE OF THE ART

This section describes the clinical background relevant to the device. It identifies the sources used for the clinical evaluation, including applicable standards and guidance documents.

The State of the Art analysis outlines current medical knowledge. It includes benchmark devices and other available treatment options. This comparison supports the assessment of safety and performance.

SECTION 8. EVALUATION OF THE DEVICE

This section explains the type of clinical evaluation performed. It defines the safety and performance parameters assessed during the evaluation process.

When applicable, the section describes how device equivalence is demonstrated. It also identifies the sources of clinical data. These sources may include manufacturer-generated data, data from systematic literature reviews, and post-market surveillance or vigilance activities.

SECTION 9. ANALYSIS OF CLINICAL DATA

This section outlines the methods used to analyze clinical data. It evaluates safety in accordance with GSPR 1 to 8 and performance in line with GSPR 1.

The section also assesses the benefit-risk profile and the acceptability of undesirable side effects, as required by GSPR 8. Any additional clinical claims are reviewed and supported with appropriate evidence.

SECTION 10. CLINICAL DEVELOPMENT PLAN

SECTION 11. ADDITIONAL ITEMS FROM APPENDIX II OF MDCG 2020-6 (LEGACY DEVICE)

This section describes planned or ongoing pre-market and Post-Market Clinical Follow-up (PMCF) investigations, when applicable. It explains how these activities support the clinical evaluation over the device lifecycle.

SECTION 12. PMS AND PMCF PLANS
SECTION 13. FREQUENCY OF CLINICAL EVALUATION UPDATES
SECTION 14. DATES AND SIGNATURES
SECTION 15. ANNEXES

This clinical evaluation plan template provides a structured guide to the essential elements of a CEP. It supports consistent documentation of device description, clinical data requirements, benefit-risk analysis, and post-market clinical follow-up activities.

Why use this Clinical Evaluation Plan Template?

This clinical evaluation plan template provides a structured and practical framework for preparing a compliant CEP. It supports consistent documentation of device description, clinical data requirements, benefit-risk analysis, and post-market clinical follow-up activities. As a result, it helps manufacturers meet regulatory expectations and maintain clinical evidence throughout the device lifecycle.

If you need help preparing your clinical evaluation plan template or developing a compliant Clinical Evaluation Plan, contact us to discuss your project and regulatory needs.