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

8. Identification of pertinent data (Stage 1)

8.1. Data generated and held by the manufacturer

Data generated and held by the manufacturer typically include the following items (not a complete list):

  • All pre market clinical investigations
  • All clinical data generated from risk management activities and the PMS programmes which the manufacturer has implemented in Europe and in other countries, including the following items (not a complete list):
    • PMCF studies, such as post market clinical investigations and any device registries sponsored by the manufacturer
    • PMS reports, including vigilance reports and trend reports
    • the literature search and evaluation reports for PMS
    • incident reports sent to the manufacturer (including the manufacturer’s own evaluation and report)
    • complaints regarding performance and safety sent to the manufacturer, including the manufacturer’s own evaluation and report
    • analysis of explanted devices (as far as available)
    • details of all field safety corrective actions
    • use as a custom made device
    • use under compassionate use/ humanitarian exemption programs
    • other user reports
  • Relevant pre-clinical studies (e.g. bench test reports including verification and validation data)

With regard to those data:

  • All data generated and held by the manufacturer need to be identified.
  • Complete data need to be entirely disclosed and made available to the evaluators; this includes data from Europe and other countries; it includes clinical studies as well as use data.
  • All data sets should be documented (adequately summarised11, appraised, analysed and referenced) in the clinical evaluation report.

8.2. Data retrieved from literature

Literature searching is used to identify data not held by the manufacturer that are needed for the clinical evaluation.
Literature searching identifies potential sources of clinical data for establishing:

  • Clinical data relevant to the device under evaluation, which are data that relate either to the device under evaluation or to the equivalent device (if equivalence is claimed).
  • Current knowledge/ the state of the art.
    Includes applicable standards and guidance documents, data that relate to benchmark devices, other devices, critical components and medical alternatives or to the specific medical conditions and patient populations intended to be managed with the device. The data are typically needed in order to
  • describe the clinical background and identify the current knowledge/ state of the art in the corresponding medical field,
  • identify potential clinical hazards (including hazards due to substances and technologies, manufacturing procedures and impurity profiles),
  • justify the validity of criteria used for the demonstration of equivalence (if equivalence is claimed),
  • justify the validity of surrogate endpoints (if surrogate endpoints are used).

The following aspects should be considered for literature searching:

  • The searching strategy should be thorough and objective, i.e. it should identify all relevant favourable and unfavourable data.
    For some devices, clinical data generated through literature searching will represent the greater part (if not all) of the clinical evidence. Thus, when conducting a literature review a comprehensive search should be conducted. If a comprehensive search is not deemed necessary, reasons should be documented.
  • Several searches with different search criteria or focus are usually necessary to obtain the necessary data. For additional information, see Appendix A4 (Sources of literature).
  • A literature search and other retrieval of data are carried out based on a search protocol. The search protocol documents the planning of the search before execution. For additional information, see Appendix A5 (Literature search and literature review protocol, key elements) and Appendix A6 (Appraisal of clinical data – examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety).
  • Once the searches have been executed, the adequacy of the searches should be verified and a literature search report should be compiled to present details of the execution, any deviations from the literature search protocol, and the results of the search.
  • It is important that the literature search is documented to such degree that the methods can be appraised critically, the results can be verified, and the search reproduced if necessary.

Abstracts lack sufficient detail to allow issues to be evaluated thoroughly and independently, but may be sufficient to allow a first evaluation of the relevance of a paper. Copies of the full text papers and documents should be obtained for the appraisal stage.
The literature search protocol(s), the literature search report(s), and full text copies of relevant documents, become part of the clinical evidence and, in turn, the technical documentation for the medical device.

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