Inhaltsübersicht

Inhaltsübersicht

1. Introduction
2. Scope
3. References
4. Definitions
5. Abbreviations
6. General principles of clinical evaluation
6.1 What is clinical evaluation?
6.2. When is clinical evaluation undertaken and why is it important?
6.3 How is a clinical evaluation performed?
6.4 Who should perform the clinical evaluation?
7. Definition of the scope of the clinical evaluation (Stage 0)
8. Identification of pertinent data (Stage 1)
8.1 Data generated and held by the manufacturer
8.2 Data retrieved from literature
9. Appraisal of pertinent data (Stage 2)
9.1 General considerations
9.2 The appraisal plan
9.3 Conduct of the appraisal
10. Analysis of the clinical data (Stage 3)
10.1 General considerations
10.2 Specific considerations
10.3 Where demonstration of conformity based on clinical data is not deemed appropriate
11. The clinical evaluation report (CER, Stage 4)
12. The role of the notified body in the assessment of clinical evaluation reports

Anhänge

A1 Demonstration of equivalence
A2 When should additional clinical investigations be carried out?
A3 Device description – typical contents
A4 Sources of literature
A5 Literature search and literature review protocol, key elements
A5.1 Background to the literature search and the literature review
A5.2 Objective
A5.3 Methods
A6 Appraisal of clinical data – examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety
A7 Analysis of the clinical data – compliance to specific Essential Requirements
A7.1 Conformity assessment with requirement on safety (MDD ER1 / AIMDD ER1)
A7.2 Conformity Conformity assessment with requirement on acceptable benefit/risk profile (MDD ER1 / AIMDD ER1)
A7.3 Conformity assessment with requirement on performance (MDD ER3 / AIMDD ER2)
A7.4 Conformity assessment with requirement on acceptability of undesirable side-effects (MDD ER6 / AIMDD ER5)
A8 Devices for unmet medical needs – aspects to consider
A9 Clinical evaluation report – proposed table of contents, examples of contents
A10 Proposed checklist for the release of the clinical evaluation report
A11 Information on declarations of interests
A12 Activities of notified bodies
A12.1 Notified body assessment of clinical evaluation by conformity assessment route
A12.2 Examination of a design dossier (Annex II.4; Annex 2.4) or of a type examination dossier (Annex III; Annex 3)
A12.3 Evaluation as part of quality system related procedures
A12.4 Notified body specific procedures and expertise

10. Analysis of the clinical data (Stage 3)

10.1. General considerations

The goal of the analysis stage is to determine if the appraised data sets available for a medical device collectively demonstrate compliance with each of the Essential Requirements pertaining to the clinical performance and clinical safety of the device, when the device is used according to its intended purpose. In order to demonstrate compliance, the evaluators should

  • use sound methods; • make a comprehensive analysis;
  • determine if additional clinical investigations or other measures are necessary;
  • determine PMCF needs.

10.2. Specific considerations

a. Use sound methods

A literature review that describes current knowledge/ the state of the art should be prepared with relevant literature identified during Stage 1 and appraised during Stage 2. Weighting criteria developed and assigned during the appraisal stage can be used to identify those sets of data, which may be considered to be pivotal. The methods available for analysing clinical data generally are either qualitative or quantitative. Depending on the nature of the medical device and the circumstances, it is likely that qualitative (i.e. descriptive) methods will need to be used for some devices. Reliance on qualitative methods should be justified. Generally, available clinical data such as numbers of incidents in the post market phase should be assessed quantitatively in relation to current knowledge/ the state of the art. The results of the pivotal datasets should be explored, looking for consistency of results across particular device performance characteristics and identified risks. If the different datasets report similar outcomes, confidence in the robustness increases. If different results are observed across the datasets, it will be helpful to determine the reason for such differences. Regardless, all data sets should be considered and included. The reviewers should take into account the weighting attributed to data sets during Stage 2 when addressing conflicting information. Where relevant, a rationale should be given for the lack of value of a data set to the evaluation. In general, data that are not methodologically sound (such as single patient reports) should not be used for demonstration of adequate clinical performance and clinical safety of a device. For additional information, see Appendix A6 (Appraisal of clinical data – examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety). In exceptional situations, when an evaluation is based on limited data, this shall be described and justified in the clinical evaluation report. See additional information and specific considerations in Appendix A8 (Devices for unmet medical needs – aspects to consider).
b. Make a comprehensive analysis

The evaluators should:

  • Determine compliance with each of the Essential Requirements pertaining to the clinical performance and clinical safety of the device. For detailed information concerning specific Essential Requirements, see Appendix A7 (Analysis of the clinical data – compliance to specific Essential Requirements).
  • The evaluation includes
    • the adequacy of pre-clinical testing (e.g. bench testing, animal testing) to verify safety – risks to patients, users or other persons associated with the intended purpose of the device – benefits to patients
    • confirmation that the device achieves the performance(s) intended by the manufacturer, including all claims made by the manufacturer
    • confirmation of usability, that the design adequately reduces the risk of use error as far as possible, and that the design is adequate for the intended users (lay, professional, disabled or other users, if applicable)
    • adequacy of the information materials supplied by the manufacturer, including if risk mitigation measures are correctly addressed in the IFU (handling instructions, description of risks, warnings, precautions, contraindications, instructions for managing foreseeable unwanted situations)
  • Take into consideration all products covered by the clinical evaluation and all aspects of their intended purpose. Any gaps in evidence need to be identified, including in respect to information relevant to:
    • understanding the interaction between the device and the body;
    • the comprehensiveness of the available data, taking into account:
      • the entire range of products/ models/ sizes/ settings covered by the evaluation
      • the entire range of conditions of use and of the intended purpose
      • the estimated number of patients exposed to the device
      • the type and adequacy of patient monitoring
      • the number and severity of adverse events
      • the adequacy of the estimation of associated risk for each identified hazard
      • the severity and natural history of the condition being diagnosed or treated
      • current standards of care, including the availability and the benefit/risk profiles of other devices and medical alternatives
  • Assess if there is consistency and alignment between the clinical evaluation, the information materials supplied by the manufacturer, and the risk management documentation for the device under evaluation; any discrepancies should be identified in order to ensure that all the hazards and other clinically relevant information have been identified and analysed appropriately.
  • Assess if there is consistency between the documents mentioned above and current knowledge/ the state of the art.

c. Determine if additional clinical investigations or other measures are necessary The evaluators should identify additional clinical investigations or other measures that are necessary in order to generate any missing data and eliminate compliance issues. Data needed to address the identified gaps should be determined so that conclusions can be drawn with confidence in relation to conformity with the essential requirements, including:

  • evaluation of the safety, performance and the benefit/risk profile
  • compatibility with a high level of protection of health and safety (that can be determined by considering current knowledge/ the state of the art, with reference to standards and available alternatives, risk minimisation, patient needs and preferences)
  • the acceptability of any undesirable side-effects
  • the risk of use error and the adequacy of the IFU to the intended users,
  • consistency between available information See Appendix A2 for detailed information on when additional clinical investigations should be carried out.

d. Determine PMCF needs

In order to determine needs, the evaluators should describe residual risks and any uncertainties or unanswered questions. The evaluators should also include aspects such as rare complications, uncertainties regarding medium- and long-term performance, or safety under wide-spread use.

10.3. Where demonstration of conformity based on clinical data is not deemed appropriate

Where demonstration of conformity with Essential Requirements based on clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given:

  • The justification must be based on the output of the risk management process. This should include an evaluation of background clinical data identified from the literature, and an appraisal of their relevance to the device under evaluation.
  • The device/body interaction, the clinical performances intended and the claims of the manufacturer have to be specifically considered.
  • Adequacy of demonstration of conformity with the Essential Requirements based on performance evaluation, bench testing and pre-clinical evaluation in the absence of clinical data has to be duly substantiated.
  • A clinical evaluation is still required and the above information and evidence-based justification should be presented in the clinical evaluation report.

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