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Clinical Evaluation for Medical Devices

What you need to know for EU MDR

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Clinical Evaluation for Medical Devices
What you need to know for EU MDR

MEDDEV 2.7/1 Rev 4 was released in 2016 as a Clinical Evaluation guide for manufacturers
and notified bodies. Then in May 2017, the EU MDR was announced. The MDR affirms the
MEDDEV and provides further information on the clinical data requirements. This white paper
explains the key stages of clinical evaluation and what documentation is needed.

What is Clinical Evaluation?

Clinical evaluation is defined as “a methodologically sound ongoing procedure to collect,
appraise, and evaluate if there is sufficient clinical evidence to confirm compliance with the
relevant essential requirements for safety and performance when using the device according to
the manufacturer’s Instructions for Use”.

The clinical evaluation must demonstrate the safety and performance of the device.

The requirements for clinical evaluation apply to all classes of medical devices. The evaluation
should be appropriate to the device under evaluation, its specific properties, and its intended
purpose. Benefits and risks should be specified, e.g., their nature, probability, extent, duration,
and frequency. Core issues are the proper determination of the benefit/risk profile in the
intended target groups and medical indications, and the demonstration of acceptability of that
profile based on current knowledge/ the state of the art in the medical fields concerned.

Clinical evaluation is the responsibility of the manufacturer, and the clinical evaluation report is
an element of the technical documentation of a medical device. It is conducted throughout the
life cycle of a medical device, as an ongoing process.

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What are the 5 phases of Clinical Evaluation?
According to MEDDEV, the clinical evaluation consists of 5 stages.

Stage 0 – Define the scope and plan

the evaluation.

Stage 1 – Identify pertinent data.

Stage 2 – Appraise each individual

data set in terms of its scientific
validity, relevance and weighting.

Stage 3 – Analyse the data, whereby

conclusions are reached.

Stage 4 – Finalise the Clinical

Evaluation Report (CER).

Stage 0 – Defining the scope

Stage 0 scopes the clinical evaluation and plans each step. MEDDEV 2.7/1 Rev 4 requires a
documented Clinical Evaluation Plan (CEP) at this stage. Section 7 emphasizes the importance
of a CEP and details are outlined in Appendix 3. The CEP defines the scope and clinical strategy
of the clinical evaluation, considering the device's type and history.

The CEP determines if the CER will use equivalence (the test and reference devices are similar
to the extent that there would be no clinically significant difference in the safety and clinical
performance of the test device) and/or clinical data and the types of clinical data presented (ie,
bench-top testing, clinical studies, or literature). It will also reference risk assessments, IFUs,
literature, and PMS databases. The CEP should be updated as needed when the device, current
knowledge/state of the art, applicable standards/guidance documents, medical condition
managed by the device, or medical alternatives change.

The CEP needs a device overview and must describe the device, its design, indications,
intended use, warnings, potential complications, and target population. The manufacturer
should also make clinical performance and safety claims. This section covers regulatory
approvals and changes since the last report.

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Stage 1 – Identification of pertinent data

Stage 1 identifies and gathers the data to be reviewed as part of the clinical evaluation. Clinical
data includes preclinical studies, clinical studies, and clinical literature. A literature search
protocol (LSP) must identify and describe clinical literature. The MEDDEV states an LSP should
clearly define the methodology and sound strategy for the search and provide examples of
methods such as:

• PICO (patient characteristics, type of intervention, control, and outcome queries)

• PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
• MOOSE (meta-analysis of observational studies in epidemiology)

The LSP should comprise search methodology, literature sources, database search strategy,
internet search extent, search terms and limits, timeframe, inclusion/exclusion criteria, and
appraisal plan. Scientific databases, internet searches, non-published data, and scientific
literature citations may be searched for data. MEDDEV 2.7/1 Rev 4 Appendix 4 recommends
MEDLINE or PubMed. To cover devices used in the EU, Embase, Excerpta Medica, and the
Cochrane CENTRAL trials register can be utilised.

Post-market performance data should include manufacturer complaint and recall data, MAUDE
data (US), BfArM (Germany), Healthy Canadians (Canada), Swiss Medic (Switzerland), and other
relevant databases like Eudamed (when available). New devices need to include all data.
Manufacturers need to coordinate with the notified body and have enough data to show post-
market trends for existing device updates. Data identification must be thorough, verifiable, and
justify inclusion and exclusion.

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Stage 2 – Appraisal of the pertinent data
Stage 2 appraises the data found. Data must be assessed for inclusion or deletion depending on
its contribution to device safety and performance. The appraisal process should evaluate each
document's quality, validity, and relevance. Next, it must systematically be weighed for
contribution to the clinical evaluation using a systematic approach (Figure 1). Transparent
appraisals should contain all high-quality data, positive or negative.

Figure 1: Systematic literature review process

Include an appraisal plan with the methodological selection criteria to ensure unbiased clinical
data evaluation. MEDDEV Appendix 6 lists studies that lack scientific validity for clinical
performance and safety. Excluded papers omit techniques, products, patients, clinical
outcomes, confidence intervals, or statistical significance. Data quantity may determine
inclusion. Some devices have hundreds of meta-analyses and randomised clinical trial data,
while others have only single-centre observational studies.

Stage 3 – Analysis of the clinical data

Stage 3 assesses conformity requirements. Previously, with the essential requirements (ERs) 1, 3,
and 6 of the MDD and now for general safety and performance requirements (GSPRs) 1, 5, and 8 of
the MDR:
• ER 1 = GSPR 1 and 5
• ER 3 = GSPR 1
• ER 6 = GSPR 8

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Data should show that clinical evidence meets all of the above requirements.

The clinical data for each requirement but be analysed to determine that the device is designed
and manufactured to ensure patient and user safety. It should also meet the “state of the art”
(SOTA) products that are developed and approved for sale in the marketplace. To ensure all
identified hazards are addressed by relevant standards and any gaps are covered by clinical data,
the data should be reviewed using risk management documents.

The manufacturer must correctly identify the medical conditions and target groups the device
will treat and demonstrate clinical evidence of the patient benefits. The data should also show
an acceptable benefit/risk profile for the intended purpose. Patient risks must be minimised
and acceptable when weighed against patient benefits.

Any residual risks, uncertainties and concerns should define post market clinical follow up
needs.

Stage 4 – Clinical evaluation reporting

Stage 4 concludes the clinical evaluation by documenting each phase and assessing the device’s
safety and performance. For more information, consult the MEDDEV's sample table of contents in
Appendix 9. Below is a table of contents summary.

1. Summary: This is a summary of the report and should include the guidance being
conformed to (MDR), a benefit/risk profile, target groups, medical indications, and device
profile acceptability based on the state of the art.

2. Scope of the clinical evaluation: The manufacturer must list information and provide
images for the device, accessories, name/address, and physical and chemical
characteristics. IFU information such as indications, warnings and complications should
also be included.

3. Clinical background, current understanding and state of the art: This should include a
literature search including the methodology, sources and appraisal criteria. State of the art
information is crucial in justifying the device in its intended market. Similar and
competitive devices should also be described here along with their risks and benefits.
Further to this, a description of the medical condition, population, alternatives to the
device being used, users and unmet medical needs should also be included.

4. The device under evaluation: The type of evaluation must be stated along with information
on what it’s based on, demonstration of equivalence (if applicable), and the conclusion(s).

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5. Conclusions: This section of the CER should state compliance to the MDR with the
acceptability of the benefit/risk profile according to both current knowledge and state of
the art. The manufacturer must also list how they will follow up and report on the finding
post market.

6. The next clinical evaluation date and how it was determined based on the device class and
how well established it is.

Key considerations
We advise taking some key questions into consideration when undertaking your clinical evaluation:

• Are your clinical evaluation reviewers “qualified”?

• Do you have all evaluators' CVs and declarations of interest?
• Have you searched multiple databases and methodologically explored clinical literature for
state of the art and clinical data?
• Do the report’s findings have “sufficient” clinical evidence?
• Are conformity to all GSPRs stated and inconsistencies noted?
• Do you have a Clinical Evaluation Plan (CEP), A Post Market Surveillance (PMS) Plan, and a
Post Market Follow Up (PMCF) Plan?

CLIN-r+ recommendations
We know that the new regulations and all that clinical evaluation now entails can be
problematic. Clinical Evaluation has evolved from a simple process and report to a detailed
justification of your medical device and critical review of its safety and performance. Clinical
data from trials and comprehensive literature searches must support the evaluation.

Clinical evaluation, including the CEP, CER, literature searches and report is a key component of
the MDR Technical Documentation which must be done to obtain CE marking.

Should you have any questions or need professional assistance, CLIN-r+ has a wealth of
experience in clinical evaluations and literature searches to call upon. Get in touch!

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