Clinical evaluation of medical devices is a systematic and planned process that contributes to the continuous generation, collection, analysis, and evaluation of clinical data for a given device. This also verifies the safety and performance, including clinical benefit, of a device for the use intended by the manufacturer. In the MDR, the scope and weighting of clinical evaluation is more important than in the MDD. The clinical evaluation is part of the medical device development process and must be compliant with the Essential Safety and Performance Requirements (GSLA) in order for the device to be approved and receive the CE mark. Thus, every medical device manufacturer actually has to go through this process with their product.

Clinical evaluation requirements and objectives

The main goal of any clinical evaluation is to demonstrate the safety and performance of the medical device in clinical use. As part of the conformity assessment process to obtain CE marking, it is an important process. There are some guidelines/standards apart from the MDR that must be followed when preparing the clinical evaluation, such as MEDDEV 2.7/1 Rev. 4 (2016), MDCG 2020-5 and 2020-6, or requirements from ISO 14155.

Main requirements:

Traceability of the literature search by specifying search terms, links, and databases searched (at least two databases such as Embase or Pubmed must be included).

Comprehensible criteria for all steps (inclusion, exclusion, evaluation, definition and documentation of applied criteria)

Consideration of positive and negative results, objectivity must be given

Evaluation of the literature

Selection of high quality publications, evaluation of significance of individual publications

Evaluation according to quality and publication

Comparability of the evaluated product in technical, clinical and biological aspects

The evaluating persons must have appropriate qualification (medical knowledge, knowledge about application of the product, experience with scientific literature research)

The required update of the clinical evaluation thus results in two phases: Pre-market and post-market of the medical device. In the pre-launch phase, the manufacturer of a medical device must prove that it meets the specified performance and is safe in order to obtain marketing authorization. This must be followed by clinical evaluation. For implantable devices and Class III devices, clinical evaluation is required unless the use of pre-existing clinical data is sufficiently justified (MDCG 2020-6 and Risk Management). It is the clinical evaluation that justifies certain risk management actions and is therefore an essential part of this. After market introduction, the clinical evaluation must be updated through ongoing monitoring with regard to clinical performance and safety. In particular, technical adaptations and optimizations of the product must be re-evaluated as well as data from post-market surveillance of the own product and data from the product group under consideration.

Clinical evaluation and the MDR

In the MDR, clinical evaluation is regulated in Article 61 and Annex XIV, and the term itself is also defined in the definitions. Due to the change from the MDD to the MDR, there are also a few implications for clinical evaluation, but basically the clinical evaluation should still be able to be based on existing clinical data.

Updating throughout the product life cycle is still required

For Class III devices and implants, clinical data should generally come from clinical trials; however, the MDR allows for exceptions in certain constellations, see also MDCG 2020-5

An exception for active implantable medical devices is not applicable

For class III devices and some class IIb devices, an authority or expert panel may additionally be consulted to “review the clinical development strategy and clinical trial proposals” (Article 61, paragraph 2 MDR)

The MEDDEV 2.7/1 Rev. 4 (2016) and the MDCG 2020-5 and 2020-6 as guidelines.

When implementing the clinical evaluation requirements, one proceeds according to the guidance in the MEDDEV 2.7/1 Rev. 4 (2016) and the MDCG 2020-5 and 2020-6 guidance documents. These guidelines are universally recognized by Notified Bodies and have stringent requirements for demonstrating medical device safety and performance, device equivalence, and clinical data from legacy devices. An important aspect is the continuous updating of data throughout the product life cycle!

According to the guidelines, one should follow the following steps in the clinical evaluation:

Step 0: Planning

Outline the objective and structure of the clinical evaluation, classification of product development (known/new technology, new application), intended use.

Step 1: Identification

Collect clinical data, consider equivalence, possible sources: scientific literature, clinical experience, clinical trial

Step 2: Assessment

Individual evaluation of data, assessment against established criteria (Is source safe? Does source provide information on benefits and safety of product?)

Step 3: Analysis

Overall evaluation of relevant data to assess whether evidence of medical device performance and safety is given. Criteria: Significance of data, conclusions on benefits and safety of product; qualitative or quantitative evaluation possible.

Step 4: Report

Logically structured report on the evaluation with justifications and documentation of the steps, documents all individual steps (Clinical Evaluation Report)

General principles of the MEDDEV:

Requirement: clinical evaluation must be actively updated. At least annually for medical devices with significant risk or devices that are not yet well established. Every 2-5 years for devices not expected to be high risk. The update usually coincides with a Notified Body audit and/or certificate renewal.

The new data for the update usually come from post-market clinical follow-up (PMCF).

Confirmation: Clinical evidence is still available that confirms compliance with GSLA, including clinical safety and clinical performance.

Confirmation: Conformity between the data from the analysis and the current state of the art is present.

The importance of the MEDDEV is thus great as a guideline for manufacturers and notified bodies. In terms of content, requirements are taken from the EU regulations/directives, thus also describing the requirements for the performance and documentation of the clinical evaluation. In addition, the guideline contains examples for the documentation of the literature search, evaluation and analysis of clinical data. Although this guideline is not legally binding, its use is (still) expected.

Data from the following areas must be included in the assessment:

Regulatory Affairs

Literature review

Design dossier / technical specifications

Risk/benefit assessment

Pre-clinical studies

Clinical trial on the actual or equivalent product

Post market surveillance on own product as well as at least one equivalent product (if applicable).

Data for a clinical evaluation can be obtained as follows: Through

Scientific literature:

E.g., published/unpublished studies on similar product with evidence of similarity in biological, clinical, and technical aspects, professional literature, recommendations for action from professional societies, etc.

Clinical experience data:

Clinical experience related to the product, e.g., post-market surveillance data with predecessor product and/or from competitive products, post-market clinical follow-up studies (e.g., observational study) with own product

Clinical Trial:

Data collected through a clinical trial itself

General principles of MDCG 2020-5 and 2020-6.

In the same wording as the MDR, MEDDEV 2.7/1 Rev.4 requires that technical, biological, and clinical characteristics must be considered in the evaluation of equivalence when preparing a clinical evaluation based on the equivalence principle. Differences between MDR and MEDDEV 2.7/1 Rev. 4 arise in the criteria for evaluating these three characteristics, which are addressed in the MDCG 2020-5 “Clinical Evaluation – Equivalence: A guide for manufacturers and notified bodies” document. MDCG 2020-5 also addresses the limits of the basic admissibility of the equivalence procedure. This concerns manufacturers of Class 3 devices and implantable devices. The equivalence assessment is only permissible at all in two case constellations, irrespective of the content of the equivalence assessment. In all other cases, proof of safety and clinical performance can only be provided on the basis of clinical trials.

For devices without medical use according to Annex XVI of the MDR, such as contact lenses or devices for transcranial stimulation of the brain, clinical investigations should in principle be performed, unless clinical data of an analogous medical device are available; analogous means product with similar technical basis and risk profile, but with medical use.

MDCG 2020-6 “Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC” identifies recommended actions to facilitate the identification of clinical data to demonstrate compliance with the essential safety and performance requirements needed as part of the technical documentation for medical devices already on the market. First, the term “legacy device” is defined, and second, a characteristic definition of the term “well-established technology” is provided. Although the MDR does not explicitly define the term “sufficient clinical data”, MDCG 2020-6 indicates that it is ultimately understood to mean the result of a qualified evaluation that allows the conclusion that the medical devices under consideration are safe and fulfill the intended medical benefit. Furthermore, it is emphasized that this evaluation, like the conduct of the clinical evaluation itself, is an ongoing process and can never be understood as a snapshot in time.

The two MDCG documents are currently to be read in conjunction with MEDDEV 2.7/1 Rev. 4 and should not be used independently as guidelines for the preparation of a clinical evaluation according to MDR requirements, but rather as an aid for the practical implementation of the requirements.

Preparation of clinical evaluations

For the further process of conformity assessment, it is not only important that a well-founded clinical evaluation for a medical device is available, but it is also important how this is designed in detail. In other words, the documentation must be comprehensible and all results must be justified according to the standard of scientific work. Even negative results or results that are “unusable” for the purpose of the product must not simply be filed away, but must be listed with logical justification and, if necessary, excluded. Thus, it is important to comply precisely with the requirements for clinical evaluation, because this can also be a crucial point in an audit.

And for high-risk devices (Class III and Class IIb implants), even greater care is required here, because: A reference to the “Brief Safety and Clinical Performance Report” must be on the label or instructions for use, so that users can inform themselves as best they can. And the results from the clinical evaluation and the brief report must be sufficiently stated in the instructions for use.

If you need assistance in preparing the documents, please feel free to contact seleon gmbh. With a team of experienced experts, some of whom have practical experience in the medical field, we can provide you with a framework that will successfully guide you to a clinical evaluation that complies with the requirements!

Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.