Benefit/Risk Ratio

A Clinical Evaluation Report (CER) is not complete without a proper benefit-risk determination, defined in EU MDR 2017/745 Article 2(24) as the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer. According to Article 2(53), clinical benefit means 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.

These two articles lay the foundation for Chapter VI Article 61(1), according to which conformity needs to be confirmed with General Safety and Performance Requirements (GSPRs) that are relevant to the device when used as intended under normal conditions, to determine the acceptability of the benefit/risk ratio. In line with this, Annex I Chapter I Section 1 states that medical devices must be safe and effective, while not compromising the clinical condition of the patient or the safety and health of users. Any risks associated with the device must be weighed against the benefits to the patient, taking into account the generally acknowledged state-of-the-art (SOTA). Furthermore, Annex I Chapter I Section 8 mandates that all known and foreseeable risks, including undesirable side effects, are minimized and deemed acceptable when weighed against the evaluated benefits to the patient and user.

This critical assessment is based on ISO 14971, which instructs device manufacturers to reduce risks as far as reasonably possible, so that the claimed benefits of the medical device outweigh any risks and potential side effects, with respect to the SOTA, including competitor devices and alternative treatment options that are available to the patient.

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Post-Market Clinical Follow-up Templates

Portfolio expansion – Clinical Study Templates now also offers Post-Market Clinical Follow-up Plan (PMCFP) and Post-Market Clinical Follow-up Report (PMCFR) templates as part of the clinical evaluation process required to place and/or retain Class I-III medical devices on the EU market. These templates are designed to strategize and document post-market clinical data collection in support of the clinical evaluation of a medical device on the EU market. These templates are fully compliant with the EU MDR 2017/745 required content and section order, as recommended per the MDCG 2020-7 and 2020-8 guidelines.

The new templates are a valuable addition to the existing portfolio of Clinical Evaluation Report (CER) and Clinical Evaluation Plan (CEP) templates that are compliant with the EU MDR 2017/745 and follow the MDCG 2020-6 guidelines, as expected by the Notified Body.

For more information, visit: https://clinicalstudytemplates.com/clinical-evaluations-mdr/

Equivalence

Claiming equivalence per EU MDR 2017/745 Annex XIV Part A paragraph 3 may seem like an attractive route to obtain clinical evidence for a device under evaluation. However, Notified Bodies tend to be rather reluctant to declare conformity, if safety and performance are not supported with primary clinical data generated for the subject device itself.

MDCG 2020-6 Appendix III regards clinical trials as the highest level of evidence, while equivalence data ranks number 5 on the 12-rung ladder, thereby falling just below the cut-off minimum of level 4 that is expected for Class III legacy devices and implantable legacy devices that cannot be considered well-established technologies (WETs).

Still, claiming equivalence can be a viable option to retain a medical device on the regulated EU market, in the absence of sufficient high-quality clinical data pertaining to the subject device itself. If manufacturers decide to follow that strategy, EU MDR 2017/745 Annex XIV Part A paragraph 3 (as elaborated on in MDCG 2020-5) states that equivalence mandates Technical, Biological, and Clinical aspects to be either the same or similar to those of the device for which equivalence is claimed (see the equivalence table below).

Beware that, when providing justifications as to why any differences do not impact the safety or clinical performance of the subject device, the Notified Body expects to find the Clinical Evaluation Plan (CEP) clearly defining a comprehensive strategy, and the Clinical Evaluation Report (CER) to contain solid evidence (e.g., in the form of scientific articles) accompanying the submission.

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Scientific Literature

EU MDR 2017/745 Article 61(3a) and Annex XIV Part A Paragraph 1(b) require manufacturers to conduct a methodologically sound and critical assessment of the current scientific literature relating to the safety and performance of a medical device as part of its clinical evaluation.

MEDDEV 2.7/1 Rev. 4 Section 8.2 dictates that the literature search follows a Literature Review Protocol (LRP) that outlines the strategy per Appendix A5. As stated in Appendix A4, the search is expected to be executed in multiple databases, such as PubMed and Embase, after which the retrieved articles are subjected to a selection process based on predefined inclusion/exclusion criteria (Appendix A5.3). This collection process is documented in the associated Literature Review Report (LRR) in accordance with the overall Clinical Evaluation Plan (CEP).

The selected articles are then appraised for suitability (i.e., appropriateness of: Device, Application, Patients, Reporting – DAPR) and data contribution (i.e., source Type, Outcomes, Follow-up, Statistics, Clinical significance – TOFSC) according to IMDRF MDCE WG/N56FINAL:2019, and for level of evidence (i.e., level I to V) in accordance with OCEBM 2011. Ultimately, the findings are summarized in the Clinical Evaluation Report (CER) as part of the collective clinical evidence that supports the safety and performance of the subject device.

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Literature Review Templates

Portfolio expansion – Clinical Study Templates now also offers Literature Review Protocol (LRP) and Literature Review Report (LRR) templates including an Excel Worksheet to organize the literature as part of the clinical evaluation process required to place and/or retain Class I-III medical devices on the EU market. These templates contain all the essential aspects for European Union (EU) Medical Device Regulation (MDR) 2017/745-compliant submissions to the Notified Body (NB), as recommended by the MEDDEV 2.7/1 Rev. 4 and the Oxford Centre for Evidence-Based Medicine (OCEBM) guidelines on the search, identification, collection, selection, and assessment of scientific clinical literature of the subject device as well as the State-of-the-Art (SOTA), including comparator devices (i.e., similar, benchmark, and competitor devices).

The new templates are a valuable addition to the existing portfolio of Clinical Evaluation Report (CER) and Clinical Evaluation Plan (CEP) templates that are compliant with the EU MDR 2017/745 and follow the MDCG 2020-6 guidelines, as expected by the Notified Body.

For more information, visit: https://clinicalstudytemplates.com/clinical-evaluations-mdr/

State-of-the-Art (SOTA)

The State-of-the-Art (SOTA) section is considered as one of the most confusing, ambiguous, and challenging parts of a Clinical Evaluation Report (CER).

Contrary to popular believe, SOTA is not about the latest and greatest technological novelties on the regulated market. Instead, it defines the clinical landscape in which the medical device under evaluation is used in order to determine how the safety and performance of the subject device fit in and compare to competitor, similar, and benchmark devices (i.e., comparator devices) as well as alternative treatment options that are available to patients. In other words, SOTA sets the stage that allows for an objective risk-benefit profile assessment of the subject device.

The CER Template contains a pre-populated SOTA section with clear guidelines on identifying, collecting, and organizing relevant clinical and scientific information needed to establish the SOTA of your subject device, as expected by Notified Body (NB) review of CERs in compliance with the EU MDR 2017/745.

For more information, visit: https://clinicalstudytemplates.com/clinical-evaluations-mdr/