Clinical evaluation of medical devices is a systematic and planned process that contributes to the continuous generation, collection, analysis and evaluation of clinical data on a particular device. That way, it also verifies the safety and performance including the clinical benefit of a device for its intended use just as indicated by the manufacturer. In the MDR, the scope and emphasis of the clinical evaluation is more important than it was in the MDD. The clinical evaluation is part of medical device development and must comply with the general safety and performance requirements (GSLA) so that the device can be declared compliant, and CE marked. This means that every medical device manufacturer has to go through this process with his device.
Requirements and aims of the clinical evaluation
The main objective of any clinical evaluation is to demonstrate the safety and performance of a medical device in its clinical use. As a part of the conformity assessment procedure to obtain the CE marking it is an important process. Apart from the MDR, there are some guidelines/standards that must be observed when creating a clinical evaluation, such as the MDCG 2020-5, 2020-6 and as well the MEDDEV 2.7/1 Rev. 4 (2016). But also, requirements from ISO 14155, which deals with the planning and execution of clinical trials.
Main requirements:
- Literature research should be comprehensible by indicating terms, links and searched databases (at least two databases such as Embase or Pubmed must be included)
- Comprehensible criteria for all steps (inclusion, exclusion, evaluation, definition and documentation of the applied criteria)
- Considering positive and negative results, objectivity must be ensured
- Literature evaluation
- Selecting high-quality publications, evaluating the significance of individual publications
- Evaluating according to quality and publication
- Comparison of the evaluated device in technical, clinical and biological terms
- The evaluators must have appropriate qualifications (medical knowledge, knowledge on how to use the device, experience in academic literature research)
It is required to update the clinical evaluation; therefore, two phases arise as a result: before and after the placing on the market of the medical device. Before a medical device can be approved, the manufacturer must prove that it fulfils the indicated performance and that it is safe. Thereupon, the clinical evaluation must be performed. For implantable devices and class III devices a clinical investigation is required, unless.
- the device in question has been designed by modifying a product already placed on the market by the same manufacturer
- the manufacturer has demonstrated that the modified device is similar to the device placed on the market (see requirements of MDCG 2020-5) and this demonstration has been confirmed by the Notified Body
- the clinical evaluation of the device placed on the market is sufficient to demonstrate that the modified device meets the relevant safety and performance requirements
It is the clinical evaluation that justifies certain measures within risk management and therefore it is an essential part for it. After placing on the market, the clinical evaluation must be updated through continuous monitoring of clinical performance and safety. In particular, technical adaptations and optimizations of the product must be re-evaluated and data from the post-market surveillance of the own product as well as data from the observed product group must be taken into account.
Clinical evaluation and the MDR
The clinical evaluation is regulated in MDR Article 61 and annex XIV, the term on its own is also defined in the general definitions. The transition from MDD to MDR also has significant impact on the clinical evaluation, but the clinical evaluation should continue to be created based on existing clinical data.
- Updating throughout the entire product life cycle is still required
- As a general rule for class III devices and implantable devices, clinical data should be obtained from clinical investigations; however, the MDR allows exceptions in certain constellations, see also MDCG 2020-5 and Article 61(4) to 61(6b) MDR
- There is no exception for active implantable medical devices
- For class III devices and some class IIb devices, an authority or expert panel may be consulted in addition to review the “clinical development strategy and proposals for clinical investigation” (Article 61, paragraph 2 MDR)
However, clinical data are not always necessary to demonstrate compliance with general safety and performance requirements based on clinical data. Article 61(10) MDR states: where evidence based on clinical data is considered inadequate, any such exemption shall be properly justified on the basis of the manufacturer’s risk management and taking into account the specific characteristics of the interaction between the device and the human body, the intended clinical performance and the information provided by the manufacturer. This will be particularly applicable to products that belong to a low-risk class or can be assigned to the absolute “standard of care” area, i.e. simple consumer products in daily clinical routine. However, this cannot be generalized; as explained, each case must be justified accordingly.
The MEDDEV 2.7/1 Rev. 4 (2016) and MDCG 2020-5 and 2020-6 as guidelines
The implementation of the requirements for the clinical evaluation is performed along the guideline of the MEDDEV 2.7/1 Rev. 4 (2016) as well as the MDCG guidance documents 2020-5 and 2020-6. These guidelines are commonly recognised, also by the notified bodies and pose strict requirements for the proof of safety and performance of medical devices, equivalence of products and clinical data from existing products. An important aspect is the continuous update of data throughout the entire product life cycle!
According to the guidelines, the clinical evaluation should observe the following steps:
- Step 0: Planning
explain objective and structure of the clinical evaluation, classification of product development (known/new technology, new application), intended use - Step 1: Identification
collecting clinical data, possible sources: academic literature, clinical experience, clinical investigation - Step 2: Assessment
individual data evaluation, assessment according to defined criteria (Is the source reliable? Does the source give information on benefit and product safety?) - Step 3: Analysis
entire evaluation of the relevant data to assess whether proof of performance and safety of the medical device is given. Criteria: significance of data, conclusions on product benefit and safety; qualitative or quantitative evaluation is possible - Step 4: Report
Logically structured report on the evaluation including justifications and documentation of the steps, documents all individual steps (clinical evaluation report)
General principles of the MEDDEV:
- Preconditions: Clinical evaluation must be updated actively. At least annually for medical devices with significant risk or devices that are not yet well established. For devices with lower risk every 2-5 years. The update usually takes place along with an audit by the notified body and/or the renewal of the certificate.
- Usually, the new data for the update is collected from the post-market clinical follow-up (PMCF). The term PMCF also includes data from the literature on the current or updated state of the art or on equivalent/relevant similar products.
- Confirmation: Clinical evidence is still available to confirm compliance with the GSPR, including clinical safety and performance.
- Confirmation: Compliance of the data from the analysis and the current state of the art must be given.
Although no longer formally applicable, the MEDDEV is still of great importance for manufacturers and notified bodies. However, new guidelines in the field of clinical evaluation are also currently waiting in the wings, with both a “new” version of the MEDDEV guideline and an ISO standard on the subject (ISO 18969) casting their shadows ahead; initial drafts are already available and consolidate or specify the requirements of the MDR. In terms of content, requirements from the EU regulations/directives have been adopted in the MEDDEV guideline rev. 4, which also describe the requirements for the performance and documentation of the clinical evaluation. In addition, the guideline also includes examples for documenting the literature research, evaluation and analysis of clinical data. Although this guideline is not legally binding, its application is (still) expected.
The evaluation must contain data from the following fields:
- Regulatory aspects
- Literature review, both on the current state of the art and on the device group to be evaluated or equivalent/relevant similar products
- Design dossier / technical specifications
- Risk-benefit evaluation
- Pre-clinical studies/tests
- Clinical investigation on the actual or equivalent device
- Post-market surveillance with an own device and at least one equivalent device (if applicable)
Data for a clinical evaluation can be obtained as follows: Through
- Academic literature:
e. published/unpublished studies about equivalent devices with proof of equivalence in biological, clinical and technical respects, technical literature, guidance by expert associations etc. - Clinical experience data:
clinical experience, related to the product, e.g. post-market surveillance data with a previous device and/or competing products, post-market clinical follow-up studies (e.g. observational study) with an own device - Clinical investigation:
data is gathered through a clinical investigation
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 taken into account in the assessment 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 evaluation of these three characteristics, which are addressed in the MDCG 2020-5 “Clinical Evaluation – Equivalence: A guide for manufacturers and notified bodies” document. This guidance document also addresses the limits of the fundamental applicability of the equivalence route. This applies to manufacturers of class III devices and implantable devices. The equivalence assessment is only permissible in two case constellations, irrespective of its content. In all other cases, proof of safety and clinical performance will only be possible on the basis of clinical trials, subject to possible further exemptions such as those described in Article 61(6b) MDR.
For devices without a medical intended use according to Annex XVI MDR, such as contact lenses or devise for transcranial stimulation of the brain, clinical investigations should always be carried out unless clinical data of an analogous medical device are available; analogous means a device with a similar technical basis and risk profile, but with a medical intended use.
The MDCG 2020-6 “Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC” provides recommendations for action to facilitate the identification of clinical data to demonstrate conformity with the general safety and performance requirements that are required as part of the technical documentation for medical devices already on the market. On the one hand, the term “legacy device” is defined, on the other hand, a definition of characteristics of the term “well-established technology” is provided. Even though the MDR does not provide an explicit definition of the term “sufficient clinical data”, the MDCG 2020-6 points out that it ultimately depicts the result of a qualified assessment that allows the conclusion to be drawn that the medical devices under evaluation are safe and fulfil the intended medical benefit. Furthermore, it is emphasized that this assessment, like the performance of the clinical evaluation itself, is an ongoing process and can never be understood as one moment in the entire process.
The two MDCG guidance documents are currently still 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 specifications, but rather as an aid to the practical implementation of the specifications.
How to create a clinical evaluation
For the further course of the conformity assessment process, it is not only important that a well-founded clinical evaluation for a medical device is available, but also how it is structured in detail. Meaning, the documentation must be comprehensible, and all results must be based on the standard of academic discipline. Even negative or “useless” results for the purpose of the device may not simply be discarded, but must be listed with logical justification and, where appropriate, excluded. Therefore, it is important that the requirements for the clinical evaluation are strictly fulfilled, for it can be a crucial point during an audit, too.
And for high-risk devices (class III and implantable devices), even greater care is required here, because: a reference to the “Summary of Safety and Clinical Performance” must be included on the label or in the instructions for use so that both the user and the patient can obtain the best possible information. For this purpose, it is necessary to provide the most important clinical data and findings on the product in a separate section of the SSCP in a formulation that can be understood by laypersons, in addition to the information for professional users.
If you need support with creating the documents, please feel free to contact the seleon gmbh. With a team of experienced experts, some also have practical medical experience, we offer a framework that will successfully bring you to a clinical evaluation that conforms to the requirements!
Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.
