Index
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
Annex
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
7. Definition of the scope of the clinical evaluation (Stage 0)
Before a clinical evaluation is undertaken the manufacturer should define its scope, based on the Essential Requirements that need to be addressed from a clinical perspective and the nature and history of the device. This is also referred to as scoping.
The scope serves as a basis for further steps, including the identification of pertinent data. The manufacturer sets up a description of the device under evaluation, and a clinical evaluation plan.
A clinical evaluation is required to be critical4. Therefore, it needs to identify, appraise and analyse both favourable and unfavourable data.
Depending on the stage in the lifecycle of the product, considerations for setting up a clinical evaluation plan should include different aspects. Typical examples are listed below.
| Aspects (not an exhaustive list) | Before CE marking | For CE marked devices |
| The device description. For additional information, see Appendix A3 (Device description – typical contents) | X | X |
| Whether there are any design features of the device, or any indications or target populations, that require specific attention. The clinical evaluation should cover any design features that pose special performance or safety concerns (e.g. presence of medicinal, human or animal components), the intended purpose and application of the device (e.g. target treatment group and disease, proposed warnings, contraindications, precautions, and method of application) and the specific claims made by the manufacturer about the clinical performance and clinical safety of the device. | X | X |
| Information needed for evaluation of equivalence, if equivalence may possibly be claimed. | X | |
| The risk management documents of the device, e.g. the hazard identification list, clinical risks identified from the risk analysis. The scope of the clinical evaluation will need data from and cross references to the manufacturer’s risk management documents. The risk management documents are expected to identify the risks associated with the device and how such risks have been addressed. The clinical evaluation is expected to address the significance of any clinical risks that remain after design risk mitigation strategies have been employed by the manufacturer. | X | X |
| The current knowledge/ state of the art in the corresponding medical field, such as applicable standards and guidance documents, information relating to the medical condition managed with the device and its natural course, benchmark devices, other devices and medical alternatives available to the target population. | X | X |
| Data source(s) and type(s) of data to be used in the clinical evaluation. Data relevant to the clinical evaluation may be generated and held by the manufacturer or available from scientific literature. For additional information, see Section 8.1 (Data generated and held by the manufacturer), and Appendix A4 (Sources of literature). | X | X |
| Whether the manufacturer has introduced/ intends to introduce any relevant changes, including – design changes, – changes to materials and manufacturing procedures, – changes to the information materials supplied by the manufacturer (label, IFU, available promotional materials including accompanying documents possibly foreseen by the manufacturer) or other claims, – and whether the claim of equivalence to an existing device is still appropriate. | X | |
| Whether there are any specific clinical concerns that have newly emerged and need to be addressed. | X | |
PMS aspects that need6 regularly updating in the clinical evaluation report:
| X | |
| Needs for planning PMS activities. | X |
It is important to recognise that there is considerable diversity in the types and history of technologies used in medical devices and the risks posed by them. Many devices are developed or modified by increments, so they are not completely novel. It may be possible to draw on the clinical experience and literature reports of the safety and performance of an equivalent device to establish the clinical evidence, thereby reducing the need for clinical data generated through clinical investigation of the device under evaluation. Similarly, it may be possible to use compliance with harmonised standards to satisfy the clinical evidence requirements for devices based on technologies with well established safety and performance characteristics.