Clinical Evaluation under EU MDR

The clinical evaluation plan serves as the basis for the clinical evaluation report, describing the relevant data inputs and document outputs expected.

The clinical evaluation plan includes the following:

• Relevant general safety and performance requirements (GSPRs) that require support from relevant clinical data
• Intended purpose statement
• Intended target patient groups with clear
• Indications and contra-indications
• Intended clinical benefits to patients including measurable safety and performance parameters
• Methods to be used to evaluate qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects
• List of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for each indication and for the intended purpose or purpose(s) of the device
• Description of how benefit-risk issues relating to specific components such as use of pharmaceutical, non-viable animal or human tissues, are to be addressed
• A clinical development plan

Stage 0-3 are summarized in the CER and form the basis of the evidence used to demonstrate compliance with the relevant GSPRs.

Clinical evidence is identified from a number of sources. Data relevant to the clinical evaluation may be held by the manufacturer or a third party, or be available in the scientific literature, for the device in question or for comparable devices. All relevant clinical data must be identified for the subject device.

Clinical data is identified based on the strategy proposed in the clinical evaluation plan. Specifically clinical literature is identified by the literature search protocol which includes the relevant literature databases, search terms and inclusion/exclusion criteria.

In the analysis section, manufacturers should provide a brief summary of the data appraisal methods, this includes a description of how data from a given study or other source of data is determined as sufficient quality and relevance to be included in the clinical evaluation. Appraisal also includes evaluation of criteria including study design, sources of bias, peer review, relevance to subject device.

Relevant data sets should be weighted on the basis of scientific quality and relevance to the scope and objectives of the clinical evaluation for the subject devices. The acceptability of the appraisal should be in terms of:

• Methodological quality and scientific validity of articles retrieved and evaluated appropriately
• Relevance of the information to the clinical evaluation determined and documented
• Contribution of each data set to the clinical evaluation weighted according to systematic criteria

The goal of the analysis stage is to provide conclusions for the sufficiency of clinical data in the CER to address the relevant GSPRs to the subject device. Additionally clinical claims are supported with evidence and the benefit/risk determination is presented.

Conclusions will be made regarding the sufficiency of appraised data sets available for the subject device to collectively demonstrate the safety, clinical performance and/or effectiveness of the device in relation to its intended use.

Benefit-risk conclusions should include:

• Summary of the clinical benefits in relation to the meaningful and measurable patient relevant clinical outcome. Their positive impact on patient management or public health.
• Risks with clinical relevance (e.g., uncertainties or limitations of clinical data, undesirable side-effects, potential for misuse, etc.) and provide a short description (e.g. incidence, severity, duration, vulnerable patient subgroups, dose-response relationship where relevant, etc.).
• Impact of risks in relation to the clinical benefits taking into account the factors described and in particular the uncertainties in relation to available clinical data.

Depending on the device under evaluation and clinical strategy, the CER will be structured accordingly. In general, the CER includes the following sections:

• Executive summary
• Scope
• State of the art
• Evidence supporting the device under evaluation.
  • Pre-clinical data.
  • Clinical literature review.
  • Clinical investigation data.
  • Post-market surveillance and post-market clinical follow-up data.
• Data appraisal
• Data analysis
• Conclusions

The CER must be evaluated by a person or team with qualifications (relevant university degree and 5 years’ experience or 10 years’ experience) in the field of:

• Research methodology
• Information management
• Regulatory requirements
• Medical writing
• Device technology and its application
• Diagnosis and management of the conditions intended to be diagnosed or managed by
• The device, knowledge of medical alternatives, treatment standards and technology (clinical background)

The CER must undergo a defined periodic review and update to ensure that it remains current and reflects any new information or data that becomes available. This review frequency is dependent upon:

• Whether the device carries significant risks
• Whether the device is well established, taking into consideration:
  • Innovation
  • Relevant changes in clinical sciences, materials sciences or other sciences related to the device under evaluation
  • The current level of confidence in the evaluation of clinical performance and clinical safety of the device
  • The total number of devices used so far in the market, and expected reporting rates under the vigilance system
  • Whether there are risks and uncertainties or unanswered questions, in the medium or L-term, that would influence the frequency of updates
  • Design changes or changes to manufacturing procedures