How is a clinical assessment based on performance data created?

Abbreviations

MDR Medical Device Regulation; EU Regulation 2017/745

PMCF Post-Market Clinical Follow-up, clinical follow-up

CEP Clinical Evaluation Plan

CDP Clinical Development Plan

Underlying regulations

EU Regulation 2017/745 (MDR)

1 Introduction

As already described in the last blog post, the clinical evaluation for all medical devices - from Class I to Class III - is an essential step for every manufacturer of medical devices. This is derived from Article 61 of EU Regulation 2017/745 (MDR):

“The manufacturer shall determine and justify the scope of clinical evidence to demonstrate compliance with the relevant general safety and performance requirements. The level of clinical evidence must be appropriate to the characteristics of the device and its intended purpose. To this end, manufacturers shall carry out, plan and document a clinical assessment in accordance with this Article and Part A of Annex XIV."

If the “performance data” route was defined during planning in the CEP, all requirements for the process and for the creation of the clinical assessment that result from the MDR and also from MEDDEV 2.7/1 Rev. 4 must still be adhered to . How this works: This blog post provides the relevant answers .

2. The route via performance data

The way to demonstrate the clinical performance of a product through performance data has always been possible and remains so under the MDR (Article 61):

„If demonstration of compliance with essential safety and performance requirements based on clinical data is considered inappropriate, any such exception shall be based on 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 applies without prejudice to paragraph 4. In this case, the manufacturer shall duly justify in the technical documentation set out in Annex II why he demonstrates compliance with essential safety and performance requirements solely on the basis of the results of non-clinical testing methods, including performance evaluation, technical testing ( “bench testing”) and preclinical evaluation, is considered suitable .“

The decision is based on various aspects:

• the result of risk management
• the characteristics of the interaction between product and body
• proof of performance based on product evaluations (technical, in-vitro)
• the result of the preclinical assessment (initial literature search, verification tests, etc.)

This decision must be appropriately explained and documented in the clinical evaluation plan.

This route is preferred when a clinical trial offers little benefit. A typical example of this is the wooden tongue depressor, for which clinical data does not exist in the literature. In such cases, technical data such as breaking strength and workmanship indicate the safety and performance of the product.

As the equivalence route becomes less and less possible and applicable, it is becoming more and more the new standard based on performance data if there is no need to generate your own clinical data.

Below are examples of when this route makes sense:

2.1 Example – Medical Software

Most software products (Class I and IIa) are examples of products where performance data makes sense. The reasoning for this decision is as follows:

The product has been fully verified as part of the software life cycle process in accordance with IEC 62304 and all tests have been successfully completed. The testing included unit testing, integration testing, system testing and usability testing. Based on these tests, it can be shown that the product works effectively.

According to MDCG-2020-1 (Guidance on Clinical Evaluation (MDR)/Performance Evaluation (IVDR) of Medical Device Software), scientific validity is defined as the extent to which the output of the software product is valid based on the selected inputs and algorithms is associated with the desired physiological state or clinical disease. In order to provide proof of scientific validity, a literature search is carried out, which also includes proof of benefit according to the MDR as well as determining the state-of-the-art and identifying the safety and performance of the medical device.

The clinically relevant components of the system are the implementations of the algorithms/questionnaires for diagnosis or the course of therapy. The literature search focuses on scores/detection algorithms as well as on the general use of digital products in the diagnosis/therapy of the indicated indications.

Table 1: Clinical evaluation of a software product

2.2 Example – dentist chair

Another product whose clinical performance, safety and benefits can be easily assessed using performance data and for which a clinical test makes no sense is the dental treatment unit: the dental chair.

Such products are active medical devices that are used to treat children and adults in the dental field. These products are dental treatment devices according to ISO 7494 with a dental patient chair according to ISO 6875. They are intended exclusively for use in dentistry and may only be operated by medical professionals. The dental treatment unit is used as an aid for patient positioning and for treatment in the dental field. Depending on whether dental instruments are part of this treatment unit and, if so, which ones, these products are classified in class IIa or IIb.

Due to the clear intended purpose of these products, the question of whether a clinical trial should be carried out on humans is unnecessary. The claims about the product relate to the ergonomics for both the patient and the practitioner and user of the product. It also emphasizes efficiency and ease of operation, and prescribed procedures and supporting components to facilitate infection control and maintain water quality. These statements are not suitable endpoints for a clinical trial. However, they can be supported with performance data. For example, the topic of ergonomics and ease of use can be proven via the usability test (DIN EN 62366-1). Compliance with the relevant standards and regulations on water hygiene and quality also confirms these claims about the product. The reason for choosing the path based on performance data is now listed here in Table 2:

Table 2: Clinical evaluation of an active product

2.3 Example – Heart rhythm detector

Another example is a Class IIa product that can detect episodes of irregular heart rhythm suggestive of atrial fibrillation through long-term monitoring of pulse parameters over several days to four weeks. It therefore supports the diagnosis by providing evidence of atrial fibrillation.

This product is based on embedded software whose algorithm recognizes the episodes and displays them accordingly. The verification and validation of the software already provides crucial data on how this medical device works. Despite the possibility of conducting a clinical trial on humans, ethical concerns must also be taken into account. An ethics committee examines precisely these aspects. However, there are alternative ways to generate clinical data to support the clinical performance and function of the product. For example, episodes can be played via simulation tests to check whether the algorithm recognizes them correctly. Here, too, no human study is required to provide this proof. The rationale for this route is shown in the table below:

Table 3: Clinical evaluation of cardiac rhythm detector

2.4 Example – Dental Implant

Even with an implantable product, this can be a viable option, as our last example from dental technology shows: The titanium base is part of a dental implant, a class IIb implantable medical device. The titanium base is used to create an individually manufactured implant prosthetic structure. After bonding with a CAD/CAM milled structure, it represents the connecting element to the implant. It can also be sold individually, so that a clinical evaluation must also be prepared for this product.

When conducting a literature search in the field of dental implants, you quickly come across the limitations of such system components. There is still no human study that has exclusively examined the titanium base as a test product. Only in vitro studies or studies on material properties (titanium), etc. were published. How the choice of route based on performance data is justified in this case is shown in Table 4:

Table 4: Clinical evaluation titanium base

3. Design and structure of a clinical assessment based on performance data

A clinical assessment based on performance data has essentially the same structure and design as a traditional clinical assessment of the other two routes. It therefore also includes carrying out a literature search.

The difference is that there is a more extensive section on existing performance/verification data and a section on justification in accordance with Art. 61 (10) of the MDR. This means that this route must be adequately 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 manufacturer's claims. This is documented in the form of the examples above in a dedicated section of the clinical assessment.

4. Approach this route based on performance data

A clinical evaluation based on performance data therefore begins with a detailed consideration of the preclinical data, also known as verification or performance data.

This data forms the database for this route and provides important information about the safety and performance of the medical device. This is the subject of further evaluation.

4.1 Measurable parameters

When creating a clinical assessment based on performance data, it is therefore just as important as with the other routes to create a list of claims about the product, particularly in relation to performance:

This means a “ non-exhaustive list and specification of the parameters for determining, based on the latest medical knowledge, the acceptability of the benefit-risk ratio for the various indications and the intended purpose or intended purposes of the product ”. (Appendix XIV, Part A, 1(a) of the MDR)

These claims should therefore contain measurable parameters that are derived primarily from the performance data. As already mentioned, these data provide important information about the safety and effectiveness of the medical device and are the basis for further assessment. This data must be documented, analyzed and then thoroughly evaluated.

Proof of measurable parameters is an important part of the clinical evaluation of a medical device. It results from clinical data in the state-of-the-art part of the clinical evaluation as well as the verification/performance data on the product. This data forms the basis for assessing the safety and performance of the product. By carefully analyzing and evaluating this data, informed conclusions can be drawn about the clinical performance and safety of the product.

4.2 Similar Products

When creating a clinical evaluation based on performance data, consideration of similar products plays an important role. The manufacturer should prepare a list of similar products and check whether clinical data are available for these products. This data can provide relevant information about the safety and performance of the device being evaluated. It is important that the manufacturer conducts an appropriate search of the scientific literature, in this case the state-of-the-art literature search (see below), to ensure that all relevant data is taken into account.

If clinical data for similar products are available, they should be included and evaluated in the clinical evaluation. This data may be particularly relevant for post-market surveillance/PMCF planning (MDCG 2020-13)

4.3 Literature search

The literature search also plays an essential and important role when creating a clinical evaluation based on performance data:

The focus here should be on the state of the art, taking into account data on similar or benchmark products, alternative applications and outcomes, as well as measurable parameters.

As already mentioned, a list of claims about the product must be drawn up, particularly in relation to performance, containing measurable parameters derived primarily from the performance data.

Based on the list of similar products created, the literature search is carried out to check whether clinical data for these products are available. To do this, an appropriate search of the scientific literature must be carried out to ensure that all relevant data is taken into account.

As a rule, there is little or no data about the product, which is why state-of-the-art data plays the biggest role in this route. In addition to possible data on similar products, these also refer to alternative applications and their outcomes, again in relation to the measurable parameters.

Not only can measurable parameters be derived from this, but the results of the product can also be discussed based on the performance data in relation to the measurable parameters in comparison with the state of the art.

A thorough literature search that focuses on state-of-the-art data can thus help evaluate the safety and performance of the product in the context of current scientific knowledge. This can be achieved by comparing the product's performance data with that of similar or benchmark products and by considering alternative applications and their outcomes.

It is important that an appropriate search of the scientific literature is carried out to ensure that all relevant data is taken into account. The results of the literature search should be carefully documented and analyzed in order to provide an informed discussion of the safety and performance of the product compared to the state of the art and to draw appropriate conclusions .

5. Conclusion

The performance data route is becoming more and more standard alongside clinical assessment with your own clinical data. The focus here is on the performance data and measurable parameters must be defined, which are mainly derived from the performance data. This data is important for assessing the safety and performance of the medical device. Here too, the basis is a comprehensive literature search, but with a focus on state of the art, similar products and applications.

A thorough literature search that focuses on state-of-the-art data can thus help evaluate the safety and performance of the product in the context of current scientific knowledge. This can be achieved by comparing the product's performance data with that of similar or benchmark products and by considering alternative applications and their outcomes.

It is important that an appropriate search of the scientific literature is carried out to ensure that all relevant data is taken into account. The results of the literature search should be carefully documented and analyzed in order to provide an informed discussion of the safety and performance of the product compared to the state of the art and to draw appropriate conclusions.

This route also results in a consistent and conclusive clinical assessment in accordance with the MDR requirements.

6. How we can help you

As CRO, we support you throughout the entire process of generating and evaluating clinical data and in the approval and market monitoring of your product. And we start with the clinical strategy! We also create the complete clinical evaluation file for you.

In the case of clinical trials, we consider together with you whether and, if so, which clinical trial needs to be carried out, under what conditions and in accordance with what requirements. We clarify this as part of the pre-study phase: In 3 steps, we determine the correct and cost-effective strategy with regard to the clinical data collection required in your case.

If a clinical trial is to be carried out, basic safety and performance requirements must first be met. The data from the clinical trial then flow into the clinical evaluation, which in turn forms the basis for post-market clinical follow-up (PMCF) activities (including a PMCF study if necessary).

In addition, all medical device manufacturers require a quality management system (QMS), including when developing Class I products.

We support you throughout your entire project with your medical device, starting with a free initial consultation, help with the introduction of a QM system, study planning and implementation through to technical documentation - always with primary reference to the clinical data on the product: from the beginning to the end End.

Do you already have some initial questions?

You can get a free initial consultation here: free initial consultation