Guidelines on Reporting the Clinical Trials of Medical Devices

Guidelines on Notification for Clinical Investigation of Medical Devices in Norway

December 2005

Contents:

Introduction
Purpose of the Clinical Investigation
The Legal Framework and Standard pertaining to the Clinical Investigation of Medical Devices
Terminology
Procedure for Notification
Further Information concerning the submission
Contents of a Notification

Information about the manufacturer
Information on the medical device
Information on the conditions under which the investigation is to be carried out
Information on the clinical investigation

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Introduction

Being a signatory to the EEA agreement, Norway has the same rights and obligations concerning medical devices as other member states of the European Union. The Act and Regulation relating to medical devices implement the provisions of the Active Implantable Medical Devices Directive 90/385/EEC, the Medical Devices Directive 93/42 EEC and Directive 98/79/EC on in vitro Diagnostic Medical Devices. These sets of regulations establish systems under which manufacturers must submit to the Norwegian Competent Authority information about clinical investigations carried out in Norway.

A key principle of the legal framework concerning medical devices is to ensure that each medical device in use is appropriate, which entails making certain that the medical device shall achieve its intended purpose as designated by the manufacturer, and that its use does not entail an unacceptable risk to the patient, health personnel or to any other.

Medical devices shall bear the CE marking of conformity to indicate that their manufacture conformed to the Regulations, and that they complied with all relevant Essential Requirements for items in their category.

Certification of most medical devices require a Notified Body to carry out verifications, investigations and evaluations on such devices in accordance with the Regulations. Such Bodies are independent Bodies having the necessary competence, and are designated by the Competent Authorities of each individual country.

In order to demonstrate compliance with the relevant Essential Requirements, it will sometimes be necessary to provide data in form of specifically designed clinical investigations.

According to §§ 4-5, 5-6 of the Regulations of December 15th 2005 No. 1690 relating to medical devices, notifications for clinical investigations of medical devices shall be sent to the Directorate for Health and Social Affairs, P.O.Box 7000 St. Olavs plass, N-0130 Oslo.

It must be noted that some clinical investigations may also require assessment/approval by or notifications to other authorities. Further information on this issue may be found at the homepage of the Regional Medical Research Ethics Committee:

Purpose of the Clinical Investigations

The purpose of conducting clinical investigations of a medical device, is to ascertain and record that the performance claimed by the manufacturer can be adequately demonstrated, and that the device is judged by a clinical expert to be safe to use on patients, taking into account any risks associated with the use of the device when weighed against the expected benefits.

A clinical investigation may be undertaken only when necessary documentation concerning performance and safety can not be obtained by other means than investigating the device in human subjects.

The Legal framework and Standards pertaining to the Clinical Investigation of Medical Devices

Clinical investigations are subject to:

Act of 12 January 1995 No. 6 relating to medical devices
Regulations of December 15th 2005 No. 1690 relating to medical devices
NS-EN ISO 14155 Clinical investigation of medical devices for human subjects
The Helsinki Declaration of 1964 and revisions thereof.

Clinical activities involved in such investigations are subject to

Act of 30 March 1984 No. 15 relating to public inspection of health services.

Satisfactory provisions for compensation shall be made against possible injuries that may result from clinical investigations to the patients and/or volunteers, on whom such investigations of medical devices are carried out (ref. NS-EN ISO 14155).

For further information on the requirements such clinical investigations should meet, please refer to: Directive 90/385/EEC relating to active implantable medical devices and Directive 93/42/EEC concerning most other medical devices. These documents may be viewed at the homepage of the Directorate for Health and Social Affairs:

Terminology

In the present document, the following technical terms are used as defined in NS-EN ISO 14155 Standard, concerning the clinical investigations of medical devices in human subjects:

Clinical Investigation: any designed and planned systematic study in human subjects undertaken to verify the safety and/or performance of a specific device

Clinical Investigator: individual and/or institution responsible for the conduct of a clinical investigation who and/or which takes the clinical responsibility for the well-being of the subjects involved

Principal Clinical Investigator: clinical investigator responsible for the organization of the clinical investigation at one site

Subject: individual who participates in a clinical investigation, either as a recipient of the device under investigation or as a control

Sponsor: individual or organisation who or which takes responsibility for the initiation and/or implementation of a clinical investigation

Monitor: individual appointed by the sponsor responsible for assessing the investigator’s compliance with the clinical investigation plan and for performing source-data verification

Procedure for notifications

Notifications for clinical investigations of medical devices should accord with Directive 90/385/EEC Article 10 and Annex VI and Directive 93/42/EEC Article 15 and Annex VIII (ref. Regulation relating to medical devices, §§ 4-5, 5-6).

Such a notification should include all the relevant information about the clinical investigation to be undertaken, as described in NS-EN ISO 14155 Clinical investigation of medical devices for human subjects. The notification should be accompanied by a favourable opinion of the proposed clinical investigation by the relevant Regional Medical Research Ethics Committee (ref. Regulation relating to medical devices, § 4).

If in the view of the Directorate for Health and Social Affairs there are reasons to raise grounds for objection to the investigation in question (ref. medical devices Act §4), the manufacturer/sponsor and the Clinical Investigator will be notified of the Competent Authority’s objections within sixty days (of having received the duly completed notification) (ref. Regulation relating to medical devices §§ 4-5, 5-6). The Directorate for Health and Social Affairs may raise objections if there are reasonable grounds to suspect that risks to public health or safety are unjustifiable, e.g:

a device does not satisfy relevant Essential Requirements
the clinical investigation is not subject to controls equivalent to the requirements of the relevant European Standard NS-EN ISO 14155

there exists professional opinion on the proposed clinical investigation that the risk-benefit analysis given by or on behalf of the manufacturer is inaccurate and that the investigation would represent a significant safety hazard to the patient or user
where insufficient information has been submitted to enable a proper assessment to be made

An objection by the Directorate for Health and Social Affairs to commence a clinical investigation is appealable as provided in Act of 10 February 1967 No. 00 relating to procedure in administrative cases, and as amended by Act of 19 June 1969 No. 54.

Further Information concerning Submission of a Notification

A notification for a clinical investigation of a medical device should be sent to the Directorate for Health and Social Affairs , either by the manufacturer, or his authorised representative in the EEA
The manufacturer or his representative should first seek the formal opinion of the proposed clinical investigation by the Regional Medical Research Ethics Committee for the region where the Clinical Investigator, or the Principal Clinical Investigator is located. On requesting such formal opinion, in addition to a notification set up as shown below, one should also send in a duly completed application form available from the Regional Medical Research Ethics Committee. For further information, do please visit:

The Regional Medical Research Ethics Committee will assess the points 3 and 4 of the notification as described below, in the light of information provided by the points 1 and 2

The notification, together with the recommendation of the Regional Medical Research Ethics Committee should be sent to the Directorate for Health and Social Affairs. If deemed necessary, the Directorate for Health and Social Affairs may request further information
The Sponsor and the Clinical Investigator of the proposed clinical investigation shall be informed of the decision of the Directorate for Health and Social Affairs within sixty days after the receipt of the notification.

Contents of a Notification

To facilitate dealing with your notification, do please base it on the template given below.

Indicate whether the applicant wishes to withhold certain information from the public. Openness in Public Administration Act of 19 June 1970 No. 69 generally applies.

Notifications should preferably be in Norwegian or in English. However, all the clinical information patients are legally entitled to know (the written “patient information form”), must be in Norwegian.

1. Information about the manufacturer

Date of the submission, and whether there has been previous submissions for clinical investigations in Norway of the same device
Name, address, etc. of the applicant; please indicate whether the applicant is the Manufacturer or his Authorised Representative in the EEA area
Name, address, etc. of the Sponsor
Information on any certificates the present medical device has received, or the modifications thereto, issued by a competent third party, such as a Notified Body
Information on the person who is in charge of the clinical investigation at the Manufacturer
Information on the person who is in charge of the clinical investigation at the Sponsor.

2. Information on the medical device

Generic and type-specific information about the medical device, and its risk category (I, IIa, IIb, III or active implantable; for further information on the classification, do please see the Annex IX to Directive 93/42/EEC)
All relevant information about the medical device;

A complete and illustrated technical description of the device
A description of its components
List of materials used in construction of the device; particulars of the material used on its surfaces, as well as reference to standards for materials coming into contact with the body
Technical details of its mode of action
Function of the medical device, and its mode of action
Technology the medical device represents
General method of production, specific method of sterilisation, if relevant
Description of packaging required to keep the device sterile, and to protect its fragile components, if relevant
A risk-analysis, together with an account of measures taken to minimise any existing risks (for details on risk-analysis, please see Standard NS- EN ISO 14971
Reference to the standards used for conformity assessments; standards or parts thereof, that have not been used for such assessments, and an account on how the Essential Requirements are met in the latter case
Identification of any tissues of animal origin incorporated within the device, together with information of sourcing and collection of such tissue and details with regard to standards or validation of manufacturing procedures employed for the reduction or inactivation of unconventional agents
Identification of any pharmacological components which are part of the medical device, with description of intended purpose and available clinical experience

An assessment of the technical performance of the medical device, carried out by an independent expert
An assessment of the clinical performance of the medical device, carried out by an expert, whose affiliation with the manufacturer or the Sponsor should be stated.

3.Information on the conditions under which the clinical investigation is to be carried out

A description of the medical condition involved, and of the generally recognised methods of observation, diagnosis or treatment relevant for the present clinical investigation
A brief description of clinical aspects considered to be well documented, areas open to further research, and specific areas the proposed clinical investigation is intended to investigate
A brief account of the theoretical framework of the proposed investigation
The number of patients required to take part in the clinical investigation with a statistical justification
Criteria for patient selection, inclusion and exclusion criteria and justification for including a control group, if relevant
Information on remuneration if any, to the participants in the clinical investigation and the Clinical Investigator
Duration of study (please include the proposed start- and end dates), and proposed follow-up period (with justification)
Description of data-collection methods, analytical procedures and criteria for a possible interruption of the investigation
A declaration by which the applicant undertakes to inform the Directorate for Health and Social Affairs of any adverse events during the clinical investigation
A declaration by which the applicant undertakes to inform the Directorate for Health and Social Affairs of any amendments to the study protocol.

It should be noted that alterations or changes of the device in use, set of indications, method of treatment, etc., may require a new submission

Description of how patient insurance is to be provided.

4. Information on the Clinical Investigation

Name of the Clinical Investigator; if the clinical investigation is carried out in several localities, include the name of the Principal Clinical Investigator. The investigation protocol should be signed by the Clinical Investigator, as well as the Head of the medical unit where it is to be carried out
Description of the clinical investigation, its aims and objectives
A description of the Essential Requirements which are to be addressed by the proposed investigation (ref. Annex I of the relevant directive)
A declaration that all other Essential Requirements have been duly fulfilled and how, and if not, justification for the omission
Declaration affirming that the clinical investigation shall conform to the NS-EN ISO 14155 Standard. Any deviation therefrom should be given and justified
A declaration affirming that necessary measures are taken to ensure the patients’ health and safety during the clinical investigation
A list of countries where the present medical device is planned to be tested clinically
A copy of the duly signed investigation protocol (se point 4a.).
An information brochure for the Subjects to be included , and a “Declaration of Consent” form to participate in the clinical investigation; both of these should be in Norwegian. The former should fulfil the requirements embodied in NS-EN ISO 14155, including giving the reader a description of the purpose of the investigation, the possible risks and discomfort it may entail, and informing the reader that participation is voluntary, and that one may withdraw from the clinical investigation at any time. For further information on the content of such a brochure, do please visit the home-page of the Regional Ethics Committee in Medical Research:

A declaration to affirm that a final report will be written by the Clinical Investigator, and will be available to the Directorate for Health and Social Affairs on request.

Directorate for Health and Social Affairs

PO Box 7000 St Olavs plass

N-0130 Oslo, Norway