How to Prepare Your Clinical Evaluation Plan Template in 5 Key Steps

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.

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.

1. Clinical evaluation of your medical device

The clinical evaluation shall be thorough and objective, and both favourable and unfavourable data should be considered for the Clinical Evaluation Plan.

Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose, manufacturer’s claims in respect of the device and risks of the device in question.

A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated.

Demonstration of equivalence should be based on demonstration of technical, biological, and clinical equivalence between the device under evaluation and the selected equivalent device. Notified Bodies highly recommend claiming equivalence against only one equivalent device.

According to MDR Article 61(1) and Annex XIV, manufacturers shall plan, conduct and document a clinical evaluation. The planning of the clinical evaluation shall be documented in a Clinical Evaluation Plan.

Moreover, the results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a Clinical Evaluation Report.

2. What is a Clinical Evaluation Plan?

The Clinical Evaluation Plan, also known as CEP, is a documented strategy that outlines the systematic and planned approach for assessing the safety and performance of a medical device throughout its lifecycle. 

It provides a comprehensive framework for conducting the clinical evaluation, which includes gathering and analyzing clinical data to establish the device’s conformity with the General Safety and Performance Requirements (GSPRs) outlined in Annex I of the MDR.

3. Navigating Annex XIV of MDR 2017/745: What To Consider?

According to the first section of Part A of Annex XIV of MDR, the CEP should be established and timely updated by the manufacturer to ensure that the clinical evaluation is planned , continuously conducted, and documented.

The minimum requirements of the CEP outlined in Annex XIV of MDR are:

• An identification of the GSPRs that require support from relevant clinical data.
• A specification of the intended purpose of the device.
• A clear specification of intended target groups with clear indications and contraindications.
• A detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters.
• A specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects.
• An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the indications and intended purpose of the device.
• An indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non- viable animal or human tissues, are to be addressed.
• A clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility, and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF with an indication of milestones and a description of potential acceptance criteria.

Moreover, manufacturers should also consider the following points for their Clinical Evaluation Plan:

3.1. Clinical data from systematic scientific literature review

A systematic scientific literature review should be conducted to identify available clinical data that are relevant to the device and its intended purpose.

This review should also highlight any gaps in the existing clinical evidence, ensuring a comprehensive understanding of the current knowledge landscape.

Conducting the systematic literature review based on PRISMA and PICO methodologies is recommended due to the fact these literature search methods contribute to ensure the systematicity and reproducibility of the search.

3.2. Clinical data from clinical investigations

Properly designed clinical investigations as per the Clinical Development Plan should be designed and conducted for your Clinical Evaluation Plan.

These investigations should aim to generate any new or additional clinical data necessary to address outstanding issues and further establish the safety and performance of the device.

3.3. Clinical data appraisal and suitability

All relevant clinical data should be appraised by evaluating their suitability for establishing the safety and performance of the device.

This evaluation should consider the quality, reliability, and relevance of the data, as well as the suggested hierarchy of clinical evidence for confirmation of conformity with relevant GSPRs under the MDR of Appendix III of MDCG 2020-6.

3.4. Clinical data analysis and conclusions

All relevant clinical data should be analyzed, including data from literature reviews, existing clinical studies, and newly generated data from clinical investigations.

The analysis should aim to draw meaningful conclusions about the safety and clinical performance of the device, including its clinical benefits.

This process involves rigorous data interpretation, statistical analysis, and consideration of risk-benefit assessments to support robust and evidence-based conclusions for your Clinical Evaluation Plan.

 

4. Navigating MDCG 2020-6: What To Consider?

The MDCG 2020-6 “Regulation (EU) 2017/745: Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC – A guide for manufacturers and notified bodies – April 2020” provides detailed guidance on the clinical evaluation of medical devices in accordance with the requirements of the MDR.

4.1. Documentation

MDCG 2020-6 points out that manufacturers are required to document a Clinical Evaluation Plan to meet the requirements of MDR Annex XIV, and provides further advice to successfully comply with MDR Annex XIV Section 1a:

• Identification of the relevant GSPRs.
• Specification of the intended purpose, target groups, indications, contraindications.
• Detailed description of intended clinical benefits with relevant and specified clinical outcome parameters.
• Specification of qualitative and quantitative aspects of clinical safety and performance.

4.2. Sources of clinical data

Moreover, the Clinical Evaluation Plan shall include the identified sources of clinical data, either:

• Pre-market clinical data: clinical investigation reports of the device concerned; clinical investigation reports or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated; reports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated; other pre-market data, such as case reports on experience with the use of the device in question).
• Post-market clinical data: PMS clinical data, complaint and incident reports; PMCF studies, including post-market clinical investigations; independent clinical studies conducted using the device; device registries; or data retrieved from the literature)
• New generated clinical data. 

The system of appraisal and analysis of clinical data shall also be presented in the CEP.

4.3. Minimum content

Furthermore, the minimum content for a Clinical Evaluation Plan for legacy devices is presented in Appendix II of this MDCG:

• An identification of the GSPR that requires support from relevant clinical data.
• A specification of the intended purpose of the device.
• A clear specification of intended target groups with clear indications and contra- indications.
• A detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters.
• A strategy to identify, analyze and assess alternative treatments.
• A specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects.
• An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device.
• An indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non- viable animal or human tissues, are to be addressed.
• A strategy and methodology to identify, analyze and appraise all relevant available clinical data in light of the changed definition for clinical data.
• Evidence for equivalence if clinical data from an equivalent device is included in the clinical evaluation.
• A definition of the required level of clinical evidence, which shall be appropriate in view of the characteristics of the device and its intended purpose.
• A strategy and methodology to systematically collect, summaries and assess post market surveillance data to demonstrate continuing safety and performance, and to what extent complaints with regards to safety and performance have been observed with the legacy devices.

Furthermore, Appendix III of MDCG 2020-6 provides a hierarchy of clinical evidence for confirmation of conformity with relevant GSPRs under the MDR.

This suggested hierarchy of clinical evidence ranks different types of clinical data and evidence from strongest to weakest and provides considerations to apply for your Clinical Evaluation Plan.

Taking into consideration the suggested hierarchy of clinical evidence as part of the appraisal methodology of your clinical data is recommended.

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.