Annex 7 Requirements
What are the overall basic requirements for any clinical investigation of an active implantable medical device in Europe?
Note: Good Clinical Practices
A clinical study sponsor is advised to review the newest copyrighted ISO Standard for details of the regulatory expectations on the design, management and conduct of clinical studies.
Council Directive 90/385/EEC
(5 September 2007)
Article 1
(e) ‘device intended for clinical investigation’ means any device intended for use by a duly qualified medical practitioner when conducting clinical investigations as referred to in Section 2.1 of Annex 7 in an adequate human clinical environment.
For the purpose of conducting clinical investigation, any other person who, by virtue of his professional qualifications, is authorised to carry out such investigation shall be accepted as equivalent to a duly qualified medical practitioner;
(k) ‘clinical data’ means the safety and/or performance information that is generated from the use of a device. Clinical data are sourced from:
- clinical investigation(s) of the device concerned, or
- clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated, or
- published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated.
ANNEX 7
CLINICAL EVALUATION
1. General provisions
1.1. As a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in Sections 1 and 2 of Annex 1 under the normal conditions of use of the device and the evaluation of the side-effects and of the acceptability of the benefit/risk ratio referred to in Section 5 of Annex 1, must be based on clinical data. The evaluation of this data (hereinafter referred to as clinical evaluation), where appropriate taking account of any relevant harmonised standards, must follow a defined and methodologically sound procedure based on:
1.1.1. Either a critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device where:
- there is demonstration of equivalence of the device to the device to which the data relates and,
- the data adequately demonstrate compliance with the relevant essential requirements.
1.1.2. Or a critical evaluation of the results of all the clinical investigations made,
1.1.3. Or a critical evaluation of the combined clinical data provided in 1.1.1 and 1.1.2.
1.2. Clinical investigations shall be performed unless it is duly justified to rely on existing clinical data.
1.3. The clinical evaluation and its outcome shall be documented. This documentation shall be included and/or fully referenced in the technical documentation of the device.
1.4. The clinical evaluation and its documentation must be actively updated with data obtained from the post-market surveillance. Where post-market clinical follow-up as part of the post-market surveillance plan for the device is not deemed necessary, this must be duly justified and documented.
1.5. 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 based on risk management output and under consideration of the specifics of the device/body interaction, the clinical performances intended and the claims of the manufacturer. Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.
1.6. All data must remain confidential unless it is deemed essential that they be divulged.
2. Clinical investigation
2.1. Purpose
The purpose of clinical investigation is to:
- verify that, under normal conditions of use, the performances of the device comply with those indicated in section 2 of Annex 1,
- determine any undesirable side effects, under normal conditions of use, and assess whether they are acceptable risks having regard to the intended performance of the device.
2.2. Ethical consideration
Clinical investigations shall be made in accordance with the Declaration of Helsinki approved by the 18th World Medical Assembly in Helsinki, Finland, in 1964, and amended by the 29th World Medical Assembly in Tokyo, Japan, in 1975 and the 35th World Medical Assembly in Venice, Italy, in 1983. It is mandatory that all measures relating to the protection of human subjects are carried out in the spirit of the Declaration of Helsinki. This includes every step in the clinical investigation from first consideration of need and justification of the study to publication of results.
2.3. Methods
2.3.1. Clinical investigations shall be performed according to an appropriate state of the art plan of investigation defined in such a way as to confirm or refute the manufacturer’s claims for the device; the investigations shall include an adequate number of observations to guarantee the scientific validity of the conclusions.
2.3.2. The procedures utilized to perform the investigations shall be appropriate to the device under examination.
2.3.3. Clinical investigations shall be performed in circumstances equivalent to those which would be found in normal conditions of use of the device.
2.3.4. All appropriate features, including those involving the safety and performances of the device, and its effects on the patients, shall be examined.
2.3.5. All serious adverse events must be fully recorded and immediately notified to all competent authorities of the Member States in which the clinical investigation is being performed.
2.3.6. The investigations shall be performed under the responsibility of an duly qualified medical practitioner or authorised person, in an appropriate environment.
The medical specialist shall have access to the technical data regarding the device.
2.3.7. The written report, signed by the responsible medical specialist, shall comprise a critical evaluation of all the data collected during the clinical investigation.