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 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 approved, 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 MEDDEV 2.7/1 Rev. 4 (2016), MDCG 2020-5 and 2020-6 or requirements from the ISO 14155.
- 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 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 use of existing clinical data is sufficiently justified (MDCG 2020-6 and risk management). 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 section 61 and annex XIV, the term on its own is also defined in the general definitions. The transition from MDD to MDR also has some 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 implants, clinical data should be obtained from clinical investigations; the MDR allows for exemptions under certain conditions, for details see MDCG 2020-5.
- There is no exception for active implantable medical devices
- For class III devices and some class IIb devices an authority or an expert panel may be consulted in addition “with the aim of reviewing the intended clinical development strategy and proposals for clinical investigation.” (Article 61, Subparagraph 2 MDR)
The MEDDEV 2.7/1 Rev. 4 (2016) and MDCG 2020-5 and 2020-6 as 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 Guidances 2020-5 and 2020-6. These guidelines are commonly recognised, also by the notified bodies and outline strict requirements for the demonstration of safety and performance of medical devices, as well as the equivalence of devices and clinical data on legacy devices. 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, equivalence, 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 no high 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).
- 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.
Therefore, as a guideline, the MEDDEV is of great importance for manufacturers and notified bodies. In terms of content, requirements from the EU regulations/directives have been adopted, 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 implementation is (still) expected.
The evaluation must contain data from the following fields:
- Regulatory affairs
- Literature review
- Design dossier / technical specifications
- Risk-benefit evaluation
- Pre-clinical studies
- 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:
i.e. published/unpublished studies about similar 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 when assessing equivalence when preparing a clinical evaluation based on the equivalence principle. The differences between the MDR criteria and the MEDDEV 2.7/1 Rev. 4 criteria regarding the evaluation of these three characteristics are addressed in the MDCG 2020-5 document. „Clinical Evaluation – Equivalence: A guide for manufacturers and notified bodies“. The MDCG 2020-5 also deals with the limits of the fundamental permissibility of the equivalence procedure. This concerns manufacturers of class 3 products and implantable products. The equivalence assessment is only permissible in the following two case constellations, irrespective of the content of the equivalence assessment. In all other cases, proof of safety and clinical performance will only be in posse by clinical trials.
For devices without a medical use as defined in Annex XVI of the MDR, such as contact lenses or devices for transcranial stimulation of the brain, clinical investigations should in principle be carried out unless clinical data of an analogue medical device are available. Analogue means a device with a similar technical basis and risk profile but with a medical use.
- MDCG 2020-6 "Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC", provides guidance to facilitate the identification of clinical data to demonstrate conformity with the essential safety and performance requirements of the MDR, which are required as part of the technical documentation for medical devices already on the market. First of all the term „Legacy Device“ is being defined, secondly a definition of characteristics of „well-established technology“ is included. Even if the MDR does not provide an explicit definition of "sufficient clinical data", MDCG 2020-6 points out that in the end this is the result of a qualified evaluation which allows the conclusion that the medical devices under consideration are safe and fulfil the intended medical benefit. Furthermore, it emphasizes that this evaluation, like the conduct of the clinical evaluation itself, is an ongoing process.
- 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 performing a clinical evaluation according to MDR requirements, but rather as an aid for the practical implementation of the specifications.
How to conduct 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 the high-risk products (Class III and Class IIb implants), even greater care is required here, because: A reference to the "Summary on safety and clinical performance" must be included on the label or in the instructions for use, so that the user can inform himself in the best possible way. And the results of the clinical evaluation and the summary report must be adequately presented in the Instructions for Use.
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!
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