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

A2. When should additional clinical investigations be carried out?

    • How should manufacturers and evaluators decide if there is sufficient clinical evidence?
      When clinical data are required in order to draw conclusions as to the conformity of a device to the Essential Requirements, the data need to be in line with current knowledge/ the state of the art, be scientifically sound, cover all aspects of the intended purpose, and all products/ models/ sizes/ settings foreseen by the manufacturer.
      If gaps are present that cannot be addressed by other means, clinical investigations should be planned and carried out.
    • Considerations
      Implants and high-risk devices, those based on technologies where there is little or no experience, and those that extend the intended purpose of an existing technology (i.e. a new clinical use) are most likely to require clinical investigation data.
      For compliance with Annex X section 1.1.a MDD and Annex 7 AIMDD, clinical investigations with the device under evaluation are required for implantable and class III devices unless it can be duly justified to rely on existing clinical data alone.
      The need for clinical investigations depends on the ability of the existing data to adequately address the benefit/risk profile, claims, and side-effects in order to comply with the applicable Essential Requirements. Clinical investigations may therefore also be required for other devices, including for devices in class I and class IIa, and for class IIb devices that are not implantable.
      When deciding if additional clinical investigations need to be carried out, the manufacturer should perform a detailed gap analysis. The gap analysis should determine whether the existing data are sufficient to verify that the device is in conformity with all the Essential Requirements pertaining to clinical performance and clinical safety.
      Special attention should be given to aspects such as:
  • new design features, including new materials,
  • new intended purposes, including new medical indications, new target populations (age, gender, etc.),
  • new claims the manufacturer intends to use,
  • new types of users (e.g. lay persons),
  • seriousness of direct and/or indirect risks,
  • contact with mucosal membranes or invasiveness,
  • increasing duration of use or numbers of re-applications,
  • incorporation of medicinal substances,
  • use of animal tissues (other than in contact with intact skin),
  • issues raised when medical alternatives with lower risks or more extensive benefits to patients are available or have become newly available15,
  • issues raised when new risks are recognised (including due to progress in medicine, science and technology)
  • whether the data of concern are amenable to evaluation through a clinical investigation,
  • etc.

Data on the safety and performance of other devices and alternative therapies, including benchmark devices and equivalent devices, should be used to define the state of the art or identify hazards due to substances and technologies. This will allow the clinical data requirements to be established more precisely in relation to the intended purpose of a device. Precision in this analysis and the choice of selected medical indications and target populations may reduce the amount of clinical data needed from additional clinical investigations.

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