The transition from MDD to MDR is well underway and has a major effect on numerous medical devices and their corresponding clinical evaluations. Avania is a contract research organization specializing in medical devices. Our medical writing department has extensive experience with conducting and writing clinical evaluations, and Avania has helped our clients navigate their medical devices through the transition from MDD to MDR. In this blog we provide you with a short insight on clinical evaluation and the transition from MDD to MDR.
What Is a Clinical Evaluation?
A clinical evaluation is a systematic and planned process to continuously generate, collect, analyze, and assess clinical data pertaining to the device under evaluation. The objective of a clinical evaluation is to verify the safety and performance, including clinical benefits of your device when used as intended. Clinical evaluations should be conducted for all medical devices, irrespective of their risk classification and market phase. However, the aim of the clinical evaluation may slightly differ. For example, in the pre-market phase, the needs regarding the safety and performance are established, while in the post-market phase, focus is primarily on demonstrating a continued acceptable safety and performance profile.
Clinical evaluations should be conducted throughout the life cycle of a medical device. This means that clinical evaluations should be repeated periodically, depending on the risk classification of the device and the identification of new safety and/or performance information. It is also important to note that the clinical evaluation feeds into the risk management files and post-market activities (both post-market surveillance and post-market clinical follow-up) and vice versa. It is therefore crucial that these documents are fully aligned and that changes in one of these documents most likely require updating of the other documents as well.
Medical Device Directive vs. Medical Device Regulation
Previously, clinical evaluations were conducted according to the Medical Device Directive (MDD) 93/42 EEC and the MEDDEV. However, the MDD was replaced by the Medical Device Regulation (MDR) on 26 May 2021. In addition, guidance documents written by the Medical Device Coordination Group (MDCG) will partly replace the MEDDEV guidance. Although the MDR is not drastically different from the MDD, there are some changes that may (largely) impact the clinical evaluation of your device.
Lessons Learned
We present our lessons learned for clinical evaluations under MDD vs. MDR, and how Avania can assist in conducting and writing clinical evaluations for your medical device.
1. Labeling and IFU
Labeling of your medical device does not only refer to the label on the product itself, but also to promotional materials such as a brochure or website. Information in promotional materials should be accurate and claimed performance outcomes or benefits should be substantiated by clinical data. Under MDR, more attention is focused on the assessment of labeling documents and the justification of information they hold. As such, updating this information before, during, or after a clinical evaluation may be required.
In addition, information that should be contained in the IFU has also been extended. Although also existing under MDD, defining the intended purpose, claimed clinical performance, and claimed clinical benefits of your device are now essential. As these definitions also, in part, determine the conduct and focus of the clinical evaluation, it is important to have your IFU MDR compliant. In some cases, the IFU can be less elaborate, and certain items, for example claimed clinical benefit, don’t need to be defined. Whether a device is such an exception depends on certain device characteristics, such as the risk classification and purpose of the device (medical vs. aesthetic).
Especially updating your IFU, but also assessing and updating your labeling documents, may be challenging. Avania can support with updating these documents by providing regulatory advice on items that should be covered in your IFU and language for these items.
2. Equivalence
Claiming equivalence may especially be interesting if there is no sufficient clinical data on your device, for example if your device is not yet on the market. When you claim and demonstrate equivalence, data from that equivalent device can be used as data pertaining to your medical device. Demonstration of equivalence should be based on scientific justification on the clinical, technical, and biological characteristics. Items that describe the clinical, technical, and biological characteristics should either be the same between the equivalent device and device under evaluation or may be similar. Whether items should be the same or similar is predefined in the MDCG-5 guidance document. In order to demonstrate equivalence, differences between the equivalent device and device under evaluation should be described, and a justification should be provided why these differences are not of clinical significance. In other words, differences do not have impact on the safety and performance assessment of the devices.
It should be noted that claiming equivalence is stricter for Class III and implantable devices than for Class I and II devices. This is due to the fact that for Class III or implantable devices a contract needs to be in place that allows full access to the technical and clinical documentation of the equivalent device, if the equivalent device is not marketed by the same manufacturer. In practice, this means that equivalence often can only be claimed to a device from the same manufacturer. In addition, the equivalent device should be certified under MDR. No equivalence can be claimed to devices that are certified under MDD, or to devices of which the certification has expired.
For devices that are not Class III or implantable devices, there is no need to have a contract in place for regulating the access to technical and clinical documentation between manufacturers. Rather, the manufacturer should have sufficient access to the data relating to the equivalent device. Also, equivalence may be claimed to devices that are certified under MDD, or without certification, provided that all relevant MDR requirements regarding equivalence can be met. As such, equivalence can be claimed to a predecessor device that is no longer marketed.
Claiming equivalence may be very important to have sufficient clinical data pertaining to the safety and performance of your device. However, it may be challenging to navigate through the MDR requirements for claiming equivalence and to provide sound justifications for any differences between the equivalent device and the device under evaluation. Avania has extensive experience with demonstrating equivalence under MDR. We can advise you whether it is necessary and possible to claim equivalence, and if so, provide support with demonstration of equivalence.
3. Benchmark Data
Benchmark devices, also referred to as similar devices, should be state-of-the-art medical devices for the indication for which the device under evaluation is intended. Benchmark devices are usually competitor devices with similar technology to the device under evaluation. As there are no specific requirements to benchmark devices, except that they should share similar technology to the device under evaluation, identifying benchmark devices is easier compared to claiming equivalence. In contrast with equivalent devices, data on benchmark devices cannot be used for the safety and performance of the device under evaluation itself.
Instead, benchmark devices are used to define the acceptance criteria for the device under evaluation and that is essential under the MDR. Acceptance criteria allow the objective evaluation of the safety and performance of the device under evaluation (as discussed below).
Avania can assist both in defining benchmark devices and conducting literature searches to gather data on these benchmark devices.
4. Acceptance Criteria
An objective assessment of the performance and safety of your device has become increasingly important under MDR, which is performed by defining acceptance criteria. Acceptance criteria are typically obtained from clinical data from benchmark devices (as discussed above) and provide a measure of performance and safety (for example, weighted average with 95% confidence interval, or medians with interquartile ranges). The acceptance criteria is calculated for either predefined performance and safety objectives for the device under evaluation, or calculated for performance and safety objectives that are defined by assessment of the state-of-the-art device. The performance and safety outcomes of your device that are obtained from clinical evidence can subsequently be compared with this acceptance criteria and should be within the same range or outperform benchmark devices in terms of performance and/or safety.
For devices that are in the pre-market phase for which a pre-market clinical investigation is designed, defining acceptance criteria can be helpful to determine the objectives of the clinical evaluation. Moreover, demonstrating that new devices meet or outperform the acceptance criteria is one of the essential items to obtain MDR certification.
5. PMCF
The planning and conduct of post-market clinical follow-up (PMCF) activities, which refers to all activities to gather safety and performance data on your device, is much more important under MDR. Collecting PMCF data is not only important for successful initial transmission to MDR, but remains important for continued MDR certification. PMCF activities are a component of the post-market surveillance (PMS) activities, although the approach is very different. While PMS activities are typically reactive (e.g., sales and complaint data), PMCF activities are proactive (e.g., clinical investigations, literature reviews, and registries). While there are many different PMCF activities that may be conducted to gather data, it is certainly not always necessary to conduct a clinical investigation. Deciding which activities are most suitable for your product depends on several factors, such as the risk classification, novelty of the device, and potential gaps that are identified in the clinical evaluation. Avania can advise on which activities are needed to gather sufficient clinical data, and we can support in writing PMCF plans and reports.
In conclusion, it may pose a challenge to maneuver every obstacle implementing the MDR into your clinical evaluation. With these lessons learned and in-depth experience in conducting clinical evaluations in numerous therapeutic areas, Avania is the perfect choice when it comes to the clinical evaluation for your medical device(s).