Clinical Benefits & Equivalence: A Guide to EU MDR Clinical Evaluation

There has been a lot of emphasis on how the clinical benefits of a medical device are addressed in the clinical evaluation. EU MDR defines the clinical benefit as “the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health”. The manufacturer needs to define direct or indirect clinical benefits for their device in the Clinical Evaluation Plan. For example, a diagnostic device directly benefits patients with early or accurate diagnoses of their medical condition. Similarly, an accessory medical device has indirect benefits if it facilitates a treatment procedure that alleviates symptoms. Clinical data should support direct benefits. Indirect clinical benefits may be demonstrable by evidence such as pre-clinical and bench testing data, real-world data (device registries), or clinical data from another device that is used in conjunction for achieving the intended purpose.

While defining the clinical benefits, the benefits’ nature, extent, probability, and duration should be considered according to MEDDEV 2.7/1 rev.4 Appendix A7.2 Section b. Each clinical benefit should have corresponding specific and measurable objectives. Clinical endpoints can be identified from clinical data that quantifiably demonstrate device safety and performance. For example, sensitivity, specificity, or accuracy values could be endpoints for a diagnostic device.

Acceptance Criteria from State-of-the-Art

It is now well-known that the clinical evaluation should include a comprehensive review of the current clinical knowledge and state-of-the-art relevant to the device in question. The objective is to compare the device’s benefit-risk profile in the context of other similar devices and alternatives available on the market. To satisfactorily demonstrate conformity to GSPRs, the acceptance criteria for the clinical endpoints of safety and performance must be determined from the clinical data evaluated in the state-of-the-art review from applicable standards and common specifications, clinical practice guidelines, or outcomes presented in published literature. For example, acceptance criteria for radiation safety can be derived from international standards for diagnostic radiation exposure. Similarly, the ‘treatment success rate’ reported in clinical studies can be considered acceptance criteria for a medical device’s performance.

Equivalence

The MDCG 2020-5 guidance on equivalence is a very comprehensive and suitable reference for clinical evaluation based on the equivalence pathway. Equivalence with a previous generation device or another device from the same family can be demonstrated per the template provided in the MDCG 2020-5 guidance. The focus should be on assessing differences in the clinical, technical, and biological characteristics in the context of device safety and performance. Suitable evidence and references should be provided to establish that the differences between the device in question and the device presumed to be equivalent are not clinically significant. Furthermore, while considering two or more devices as equivalent may be acceptable, comparing clinical, technical, and biological characteristics is expected with each device in the clinical evaluation. It is advisable to consider a single device as the equivalent device.

Post-Market Clinical Follow-up (PMCF)

The EU MDR considers the PMCF as a continuous process that shall be a part of the PMS Plan for a medical device. It is important to note that PMCF does not always mean a clinical investigation; other pathways for PMCF are provided in MDCG 2020-7 guidance and include activities such as well-designed user or patient surveys, monitoring registry data, systematic literature reviews, etc. The selection of the PMCF activity should be based on the type and risk category of the medical device, available clinical data, and unanswered questions related to safety and performance. The MEDDEV 2.1/2 Revision 2 guideline provides a list of criteria to determine the requirement of PMCF. The objectives of the PMCF activity should be clearly defined based on the criteria defined in IMDRF MDCE WG/N65FINAL:2021 and the outcome of the clinical evaluation for the device. The PMCF plan should include details such as timeline of initiation, data gathering, and completion, statistically estimated sample size, and the statistical approach for data analysis. The analysis of clinical data gathered through the PMCF activity should be documented in the PMCF Report (MDCG 2020-8) and considered for relevance when updating other parts of the technical file, such as Risk Management documentation or the Clinical Evaluation Report.

Key Take Away for Manufacturer

In conclusion, the EU MDR places significant emphasis on the clinical evaluation of medical devices, with a particular focus on defining the direct and indirect clinical benefits of the device. Manufacturers must consider these benefits’ nature, extent, probability, and duration and establish corresponding specific and measurable objectives. Acceptance criteria for clinical endpoints of safety and performance must be determined from the state-of-the-art review, and equivalence with other devices must be carefully assessed. PMCF is also crucial, with various pathways available. Selecting the appropriate PMCF activity based on the device’s type and risk category and defining clear objectives for the PMCF plan is essential. Overall, adherence to these guidelines is critical in ensuring the safety and efficacy of medical devices and maintaining compliance with EU MDR Regulations.