Clinical evaluation
MDR clinical evaluation
A clinical evaluation is required for every medical device, even those for which no clinical data is required to demonstrate compliance with the general safety and performance requirements of the MDR.
The extent and scope vary significantly between different products, indications and, to a certain extent, risk classes.
We offer various services for clinical evaluation.
When preparing clinical evaluations, we will also support you in developing a sensible strategy and avoiding unnecessary clinical investigations.
We create clinical evaluations for all risk classes and device types.
We update existing clinical evaluations for all risk classes and device types.
We correct existing clinical evaluations in case of a non-conformity.
Organizational project preparation
Software tools:
We use software to keep track of our projects. So, the first thing we do is set up a new project.
Software tools:
We record project efforts down to the second using software. Therefore, a new project is first created in the time tracking system.
Quality management:
As part of our quality management system, competent personnel are assigned to your project.
Operational project preparation
Project management:
Detailed planning of required project results
Project risk management:
Analysis of potential project risks with definition of measures
Customer communication:
Definition of suitable communication channels and contact persons
Quality management:
Obtaining necessary input information and documents
Project implementation
Quality management:
Internal kick-off meeting
Quality management:
Processing of the project in defined work packages
Quality management:
The results of the work packages are subject to internal quality control
External review
Customer communication:
Review of project results by our client
Quality management:
Improvement of project results, if necessary
Service release
Quality management:
Release of final project results
Customer communication:
Provision of final project results to our client
Project completion
Quality management:
Archiving of project results
Data protection:
Deletion of input documents and information
Software tools:
Archiving of the project in our project management tool
Software tools:
Archiving of the project in our time recording tool
If you have any questions or want to book a service, feel free to contact us!
Further down the page, you will find an overview of relevant content. There you can find general information on the topic.
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Further down the page, you will find an overview of relevant content. There you can find general information on the topic of clinical evaluation of medical devices.
Feel free to also take a look at our blog posts on this topic!
Table of Contents
Clinical evaluation plan (CEP)
The preparation of a CER has to be planned within a CEP – this is a mandatory requirement of the MDR. The exact contents of the plan are contained in Annex XIV, Part A, first item. These include the following points:
- an identification of the general safety and performance requirements 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 contra-indications;
- 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 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; and
- 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;
It quickly becomes clear that even the planning of a clinical evaluation is quite extensive. But the detailed requirements also have something good about them: the content to be delivered is relatively clearly addressed. In addition, MEDDEV 2.7-1 Revision 4 provides helpful information on many points. Although this refers to 93/42/EEC (MDD), the basic concept was not reinvented by MDR.
Clinical evaluation report (CER)
The CER records the work steps that have been carried out and planned in the CEP. Here, the defined and methodologically sound procedure required by Article 61 of the MDR is applied. As a result, a comprehensive document is produced which sets out the safety, performance and clinical benefit of the medical device.
The report brings together the data and findings from risk management, usability, biocompatibility, literature research and analysis, and post-marketing surveillance. On this sound basis, the safety and performance of the medical device is assessed. In addition, it is demonstrated that it has a clinical benefit, which is mandatory for the demonstration of clinical evidence.
The amount of different data alone shows how complex the CER of medical devices is. An author must be able to evaluate all this data in the right context and at the content level in order to draw correct and relevant conclusions.
Clinical data
As the name suggests, clinical evaluation is based on clinical data. Such data refers to “information concerning safety or performance that is generated from the use of a device [MDR]”. The following sources of clinical data exist:
- “clinical investigation(s) of the device concerned,
- clinical investigation(s) 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,
- clinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up; [MDR].”
A common method for identifying these data is a literature search. This involves a systematic search for published studies which can then be used as a data basis. How such a literature search is carried out is described in the following section.
Literature search
- Step 1: Analysis of the intended purpose, clinical claims, patient population, indications, contraindications, etc as inputs for the literature search.
- Step 2: Identification of data sources from which clinical data can be obtained. For example pubmed, Cochrane, Embase.
- Step 3: Creation of search terms and objective filters to obtain data on the medical device under evaluation, the equivalent products and the state of the art.
- Step 4: The identified literature is first pre-filtered at the level of abstracts and assessed for potential relevance.
- Step 5: Potentially relevant literature is now analysed in depth at full text level.
- Step 6: The clinical data obtained in the analysis of the full texts will now be used to support the clinical evidence.
Lack of clinical data
What happens if, while creating the CER, you discover that there is not enough clinical data on your medical device?
Can you create a clinical evaluation without clinical data?
“[…] where the demonstration of conformity with general safety and performance requirements based on clinical data is not deemed appropriate, adequate justification for any such exception shall be given based on the results of the manufacturer’s risk management and on consideration of the specifics of the interaction between the device and the human body, the clinical performance intended and the claims of the manufacturer. In such a case, the manufacturer shall duly substantiate in the technical documentation […] why it considers a demonstration of conformity with general safety and performance requirements that is based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, to be adequate [MDR].”
Fortunately for the patients, approval without sufficient data does not work. The principle is based on a sufficient data basis and without this, compliance with the general safety and performance requirements cannot be demonstrated.
Approval without clinical data only works in a few, special cases. However, what we have frequently observed with clients is that insufficient clinical data were identified during a clinical evaluation, which led to difficulties in obtaining approval.
The solution to the problem is ideally to adapt the literature search. It is quite possible that you have used an unfavorable combination of search terms and filters or equivalent devices. Actually, of course, you should already check during the creation of the search protocol whether it is suitable. Sometimes, however, this is difficult to do or it is simply forgotten.
If even this adaptation does not help, clinical studies or trials must be carried out to generate the necessary data. For manufacturers with valid MDD certificates, it is advisable to check during the period of validity of these certificates whether sufficient data is available for MDR.
In particular, it is much more difficult under MDR than it was under MDD to obtain data on equivalent devices. Therefore, the generation of sufficient clinical data should be started under the MDD in order not to be forced to conduct a clinical trial with an unapproved device. The associated costs for the approval of the ethics committee as well as in financial and time terms are enormous and should be avoided if possible.
Interface: Risk management
In the course of the analysis of identified data, it may happen that risks are identified in connection with the Company’s own medical device or equivalent device that were not previously considered in risk management. Therefore, after the data analysis, a reconciliation between the risks identified in the CER and the existing risk analysis is to be performed.
If new risks have been identified, these are to be fed into the RM process for analysis.
Interface: Usability
It does not occur frequently, but is possible: Literature research has identified indications or even difficulties with regard to usability. In this situation, measures may have to be derived.
Interface: Post-market surveillance (PMS)
An important source of information is, for example, public databases in which incidents involving medical devices are reported. Has anything been reported about the device under evaluation that was not considered in risk management? Have there been incidents with reference products that could also occur with your own device and were not considered?
Interface: Post-market clinical follow-up (PMCF)
The medical device CER is closely linked to your PMCF activities. Through PMCF, you generate clinical data on your product that contribute to the clinical evaluation.
PMCF can be useful under the MDD to generate sufficient clinical data for the approval of your product under MDR. Feel free to contact us on this topic and we will show you how PMCF can make your life easier.
Clinical evaluation for class I medical devices
From manufacturers who only have Class I medical devices in their portfolio, we repeatedly receive the question: “Do I even need a clinical evaluation for a Class I medical device? Under the MDD, we didn’t need it at all.”
In Germany, the MDD was adopted into national law by the German Medical Devices Act (MPG). The MPG on §19 Clinical Evaluation stated, “The suitability of medical devices for their intended use shall be demonstrated by a clinical evaluation based on clinical data in accordance with §3 number 25, unless other data are sufficient in justified exceptional cases. The clinical evaluation includes the assessment of adverse effects as well as the acceptability of the benefit/risk ratio specified in the Essential Requirements of Directives 90/385/EEC and 93/42/EEC. The clinical evaluation shall be conducted in accordance with a defined and methodologically sound procedure and shall take into account, where appropriate, relevant harmonized standards.”
The paragraph was not a backdoor way of not performing a clinical evaluation. It did, however, allow for data other than clinical data to be used in justified exceptional cases.
The same situation applies under the MDR (EU 2017/745). In Article 61 (10), this loophole for clinical evaluation without clinical data also exists. However, also only in justified exceptional cases.
So the answer to the question is: “Yes, you need a clinical evaluation for every medical device”.
Clinical evaluation for software as a medical device
The clinical evaluation for software medical devices such as smartphone apps differs from the clinical evaluation for classic medical devices. This makes sense and is understandable because the interaction between software and the patient is different from that between a classic medical device and a patient.
A software provides information, which in turn can cause harm. However, software itself cannot, for example, cause physical harm to people. After all, the software does not touch anyone.
To illustrate the different processes of clinical evaluation on software, there is the document MDCG 2020-1.
MDCG 2020-1 mainly describes three aspects
- valid clinical association
- technical Performance
- clinical Performance
The so-called “valid clinical association” is very similar to the so-called scientific validity of IVDs in the context of performance evaluation. To put it casually, it requires proof that the information provided by the software is related to a clinical condition or physiological state.
With an IVD, this is even more comprehensible. Imagine a COVID-19 rapid test. I want to use the test to detect COVID-19 infection. I now need proof of scientific validity for the IVD rapid test to prove that what I measure with the rapid test also has a correlation with a COVID-19 infection. Because if the connection does not exist, I cannot prove a COVID-19 infection with the measurement result. This then has nothing to do with the performance of the product, but simply with the fact that this type of detection is not possible.
So I also have to provide such proof for software as a medical device. Is the information provided related to the clinical condition or physiological state described in the intended purpose?
The “technical performance” describes the ability of a software to accurately and reliably provide the intended technical output from the input data made.
At this point, it is necessary to prove on a technical level that the software provides correct outputs from the respective inputs. These proofs are usually generated in the course of software development, when the algorithms of the software are checked and optimized
Therefore, the proof of clinical performance still remains. As with traditional medical devices, this requires data showing that the software has been tested for the intended use(s), target group(s), condition(s) of use, operating and usage environment(s), and with all intended user groups.
How exactly the evidence of clinical performance is to be provided must be decided on a case-by-case basis. It is important to note that Article 61 (10) of the MDR also applies here – the route for cases where evidence of compliance based on clinical data is not appropriate.
Clinical studies & investigations
The performance of clinical studies or PMCF studies is the necessary way to generate clinical data as a basis for approval for many existing products and especially for new developments. Due to the fact that there are extensive requirements in the area of GCP (Good Clinical Practice, ISO 14155 and at the legal level for the performance of clinical studies, an enormous amount of documentation is associated with this.
Some of our customers procure personnel who deal exclusively with planning and study coordination. Other customers rely on our study partner, who offers a convenient and cost-effective all-round solution for this.
MDCG documents
Although the clinical evaluation is governed exclusively by the MDR, notified bodies expect MDCG documents to be taken into account accordingly. Furthermore, these documents are extremely helpful in building a better understanding of what is expected. Good preparation is worthwhile, as any anomalies on the part of the notified body will be tracked and will therefore generate costs.
- MDCG 2024-10 Clinical evaluation of orphan medical devices
- MDCG 2020-13 Clinical evaluation assessment report template
- MDCG 2020-6 Guidance on sufficient clinical evidence for legacy devices
- MDCG 2020-5 Guidance on clinical evaluation – Equivalence
MDCG 2020-05 Equivalence
The use of data on equivalent products is a viable option to collect sufficient clinical data to demonstrate the applicable General Safety and Performance Requirements. Under 93/42/EEC (MDD), it was possible to use data from sources other than the device itself to a greater extent. At this point, the MDR leads to a situation where the data situation can become difficult for even established products.
In April 2020, the Medical Device Coordination Group (MDCG) published a document that provides guidance for notified bodies and manufacturers on equivalence.
The document aims in particular to highlight the differences between MEDDEV 2.7-1 Revision 4 and the requirements of the MDR.
Already under MEDDEV, equivalence was related to aspects of technical, biological and clinical properties of the devices. These properties are useful comparative values and remain the same under MDR.
The MDR requires the following with regard to biological properties: “The product uses the same materials or substances that come into contact with the same human tissues or body fluids, for a similar type and duration of contact and similar release properties of substances, including degradation products and leachables”. Under the MEDDEV, variations in materials were possible at this point, e.g. for products in contact with intact skin. By means of a risk assessment, components with other materials could also be regarded as equivalent if necessary. The requirement that, for example, the duration and type of contact must be similar is also new. It becomes clear that MDR is much stricter with regard to biological properties.
Clinical properties: Products under the MDR must now be used by the same type of user, for example physicians or lay users.
Technical characteristics: Products under MDR must now be used under similar conditions of use. The MEDDEV demanded that these should be identical. Furthermore, MDR demands that in the case of software, the algorithms in the compared products must be similar.
Overall, it is clear that the Medical Devices Regulation makes it extremely difficult to use equivalent products from other manufacturers. Therefore, the importance of sufficient post-market surveillance data must be emphasized at this point. This data can be generated during the validity period of the MDD certificates and can be used as a basis for approval of the MDR.
If you could not prove equivalence, it is possible to use data from similar products. Often “no longer equivalent” products are well suited for this.
You can use such data for the following purposes:
- Ensure that the risk management system is comprehensive by identifying relevant hazards and clinical risks.
- Understanding the state of the art, the natural course of disease and alternative available treatments.
- Assist in defining the scope of the clinical evaluation by identifying design features of similar devices that raise particular performance or safety concerns.
- Provide input to the design of the clinical trial or the design of the post-market clinical follow-up (PMCF) and to the post-market surveillance system (PMS).
- Identification of relevant and specified clinical outcome parameters for the intended clinical benefit based on published clinical data relating to the similar product(s).
- Definition of minimum requirements for a quantified clinical benefit considered clinically relevant and/or identification of acceptable rates of occurrence of risks and adverse events.
MDCG 2020-06 Clinical evidence for legacy devices
This document provides valuable guidance for products that were already approved under the MDD and AIMD and for which a clinical evaluation according to MDR is now to be prepared.
For many of the legacy devices there is little usable data available under MDR. One reason is that it has become more difficult to prove equivalence and thus to use data from other products. Another aspect is the fact that too many products are simply not or hardly ever researched because of their simplicity. Thus, there are hardly any publications.
So how should the respective GSPRs (General Safety and Performance Requirements), be demonstrated for such products?
How is “sufficient clinical evidence” to be proven in this situation, especially since the term is not even defined?
Document MDCG 2020-06 states that “sufficient clinical evidence” is understood as the present result of the qualified assessment which has reached the conclusion that the product is safe and provides the intended benefit. This qualified assessment is performed as a continuous process within the clinical evaluation. The Medical Devices Regulation regards the generation of clinical data and the evaluation of these data as an important part of the “life cycle approach” of a medical device.
In the first conformity assessment procedure according to MDR of your product approved under the MDD or AIMD, the clinical pre-market and post-market data of the product can be used. These must have been generated within the framework of the valid MDD/AIMD certificates. It is possible that the existing clinical data may not be sufficient in terms of the MDR. For legacy devices that have undergone a conformity assessment procedure, it is assumed that these were supported by clinical data. Post-marketing clinical data, together with the clinical data generated for conformity assessment according to the MDD/AIMDDD, form the basis of the clinical assessment procedure for legacy devices according to the MDR.
For all medical devices, whether authorised under MDD, AIMD or already authorised under MDR, the requirements for post-market surveillance (PMS) and clinical follow-up (PMCF) apply. Thus, from the date of application of MDR, some requirements of MDR are also applicable to legacy devices.
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