Clinical Evaluation Reports CERs for medical devices

What is a Clinical Evaluation Report?

A Clinical Evaluation Report (CER) is an important technical document that summarises the Clinical Evaluation of a medical device. An effective Clinical Evaluation Report describes a structured appraisal and analysis of all available clinical evidence to assess the safety and performance of a medical device.

While Clinical Evaluation is a continuous process, Clinical Evaluation Reports provide a “snapshot” of the conclusions of Clinical Evaluation at intervals dictated by the risk classification of the device. A Clinical Evaluation Report must be produced in relation to all medical devices under the EU MDR regardless of risk class.

The EU MDR - Medical Device Regulation (EU) 2017/745, fully in force from May 2021 - replaced the Medical Device Directive MDD 93/42/EC and introduced a wide range of new regulatory requirements, including for the conduct of Clinical Evaluation and the writing of CERs.

Because a properly structured Clinical Evaluation Report is a key requirement for regulatory approval of all medical devices under the MDR, it is vital that manufacturers understand the requirements for developing CERs under the new legislation. It is also important that manufacturers have access to a CER writer with sufficient knowledge and expertise to meet MDR requirements.

What are the requirements for writing a Clinical Evaluation Report under the MDR?

Article 61 of the MDR states that the Clinical Evaluation of each medical device shall be documented in a CER that must form part of the technical documentation portfolio for the device.

MDR Annex XIV Part A expands upon this requirement and provides detailed requirements for performing a Clinical Evaluation, requiring that the process:

• is based on a documented Clinical Evaluation Plan (CEP)
• identifies all clinical evidence relevant to the device, whether favourable or not
• appraises and analyses clinical data in a robust way according to a stated protocol
• establishes a plan for addressing any gaps in the clinical evidence portfolio
• reaches conclusions about the safety and performance of the medical device

Although Annex XIV Part A outlines how to perform a Clinical Evaluation, it is comparatively light on requirements for writing a CER. It states only that “the results of the Clinical Evaluation shall be documented in a Clinical Evaluation Report which shall support the assessment of the conformity of the device.”

More detailed guidance on writing CERs can be found in MedDev 2.7/1 rev 4 “Clinical Evaluation: A guide for manufacturers and notified bodies”, an advisory document published by the European Commission. It provides a useful section on CER structure but the guideline has not yet been updated (as of January 2021) to reflect changes in requirements introduced by the MDR. Because of this, adherence to MedDev 2.7/1 rev 4 alone will not be sufficient to achieve MDR compliance and manufacturers will need to use additional sources of information and expertise, discussed below, to ensure that EU MDR requirements have been met.

How should a Clinical Evaluation Report be structured?

According to MedDev 2.7/1 rev 4, a medical device Clinical Evaluation Report should include the following information as a minimum:

• details of the medical device
• a review of the clinical field the device sits within, including alternative treatments within the field and an assessment of the state of the art
• appraised clinical data relating to the device and its clinical performance
• results of Post-Market Surveillance (PMS), Vigilance system and Post-Market Clinical Follow-up (PMCF) activities
• a benefit-risk assessment
• an objective conclusion as to whether the device conforms with relevant MDR Annex I General Safety and Performance Requirements (GSPRs) and is suitable for its intended purpose

Each section should be carefully structured and precisely written to ensure that the document can be understood by an assessor who may not have specialist knowledge of the medical device.

Since the publication of MedDev 2.7/1 rev 4, further guidance has been released from the Medical Device Coordination Group (MDCG) including MDCG 2020-13 that sets out criteria against which medical device Clinical Evaluation Reports will be assessed under the MDR. This updated guidance sets out requirements for CERs under the MDR that are not covered in MedDev 2.7/1 rev 4, including:

• the requirement to analyse clinical evidence relating to comparable alternative devices in order to determine quantifiable safety and performance benchmarks against which the subject device can be assessed
• including a summary of the Clinical Evaluation Plan in the CER
• where possible, performing a statistical analysis of clinical evidence considered in the CER
• restrictions on use of medical device equivalence
• detail on how to demonstrate clinical benefit during benefit-risk profiling, including the need for purported benefits to be quantifiable and based on evidence

Under the EU MDR, a Clinical Evaluation Report should set out a robust, objective, scientific analysis of clinical evidence. Language used by a CER writer must convey a balanced appraisal of the device’s safety and performance that is sufficiently robust to meet the demands of regulatory scrutiny.

CERs are ideally written by someone who has a sufficient degree of medical, scientific and regulatory experience to achieve these requirements.

Clinical evidence in the Clinical Evaluation Report

Identification, appraisal and analysis of clinical evidence is a central requirement for writing a CER under the MDR. Clinical evidence is considered in two key components of the CER:

1. in relation to comparable alternative devices in order to establish safety and performance benchmarks against which the subject device can be compared
2. when assessing safety and performance of the subject device

All relevant clinical evidence must be identified, whether favourable or unfavourable, and must be appraised and analysed according to a protocol specified in the Clinical Evaluation Plan. There must also be specified procedures for avoiding duplication of data.

• Clinical evidence relating to the subject device comes from two sources - that generated and held by the manufacturer, and evidence produced independently and published in the literature.
• Manufacturer-generated evidence includes that generated from pre-market studies, PMS, Vigilance and PMCF activities.
• Independent evidence must be identified through a robust and documented search protocol that will contain provisions for ensuring that all relevant evidence is found.

Appraisal of evidence involves consideration of factors such as:

• suitability of method and sample size
• relevance to the subject device and its clinical evaluation
• study type and quality
• potential for bias
• suitability of statistical analysis techniques employed

Following identification and appraisal, the Clinical Evaluation Report should contain an analysis of the clinical evidence to determine whether the subject device has met its safety and performance obligations under the MDR (including in comparison to comparable alternative devices).

Effectively writing a Clinical Evaluation Report requires access to high-level expertise in identification, appraisal and analysis of clinical evidence.

What happens to a CER after completion?

Following completion, a CER will be assessed as a component of the technical documents that must be submitted in support of the device. The procedure by which CER assessment will take place depends upon the risk classification of the device.

Under the MDR, manufacturers of Class IIa, IIb and III medical devices must submit the completed CER to a Notified Body (or UK Approved Body in the UK post-Brexit) for regulatory scrutiny as a component of a conformity assessment procedure. Permission to affix a CE-mark will not be granted unless the Clinical Evaluation Report meets MDR requirements.

The MDR outlines responsibilities for notified bodies in performing assessments of Clinical Evaluation Reports, requiring notified bodies to have access to individuals with sufficient scientific and technical expertise to make a reasoned assessment of the CER. Clinical Evaluation Report assessment will follow the guidance specified in MDCG 2020-13.

Manufacturers of Class I devices do not normally need to submit CERs to a notified body for assessment. However, a Class I device is still subject to the MDR requirements to perform a Clinical Evaluation in that it must demonstrate conformity with the Annex I GSPRs, suitability for intended purpose and an acceptable benefit-risk profile. Therefore, a Clinical Evaluation Report is still required for Class I devices and should be written with a similar degree of care and skill to those required for higher risk devices.

Furthermore, some categories of Class I device have special requirements that may require an assessment by a notified body. Class I devices that are supplied sterile (Class Is), are a reusable surgical device, or have a measuring function (Class Im) will require involvement of a notified body and manufacturers of these types of devices should prepare CERs with notified body involvement in mind.

Where can I find help writing a Clinical Evaluation Report?

For devices seeking approval under the MDR, it is extremely important that CERs are produced to a sufficient standard. It is strongly advised to engage experienced CER writers who have a comprehensive understanding of EU MDR compliance requirements.

Utilising professional help can be a wise investment of resources since CERs that do not meet the required regulatory standard could result in regulatory approval for the device being withdrawn. In turn, this can lead to expensive reparative work, loss of market postion, and loss of customer confidence in the device.

Using a Clinical Evaluation Report template can be an effective way to begin drafting a CER but care must be taken to ensure that the template is comprehensive and specific to EU MDR requirements. Using a template is also dependent on medical writing expertise and an ability to identify, appraise and analyse clinical data.