Health Ethics Committee – Clinical Trials Guidance Notes
HEALTH ETHICS COMMITTEE
CLINICAL TRIALS GUIDANCE NOTES
The Health Ethics Committee (hereinafter referred to as ‘the committee’) has been appointed by the Ministry for Health to assess in both the public and private sector:
- Applications for clinical trials on medicinal products as per the Maltese Clinical Trials Regulations, 2004 (LN 490) and the European Clinical Trials Directive 2001/20/EC; and
- Applications on all other clinical trials including those involving devices and interventions.
A: Regulation of clinical trials on medicinal products
The Maltese Clinical Trials Regulations, 2004 (LN 490) may be accessed on: The European Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use may be accessed on: The legislation refers to both commercial and non-commercial trials.
In order to start a clinical trial in Malta, the committee should issue a favourable opinion and the Licensing Authority should authorize it. In order to obtain a favourable opinion from the committee to start a clinical trial an application shall be submitted to committee.
The application form should be submitted in English. Documentation attached to the application should be submitted in English and/or Maltese.
Applications
When an applicant submits an application for a clinical trial, he must fill in the application form: Request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities and for opinion of the ethics committees in the community.
The application should be prepared in accordance with the European Commission’s Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human use. The application form and guidance notes may be accessed on:
The completed application form should be submitted with section 7.2 (full data set) and section 7.3 (Module 2) of the Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human use. The applicant should also submit a soft copy of the application form. The required documentation may be seen in annex 11.
Amendments
Any amendments should be clearly identifiable.
When submitting a substantial amendment, the application form Request for authorisation of a substantial amendment to a clinical trial on a medicinal product for human use to the competent authorities and for opinion of the ethics committees in the community needs to be filled.
Substantial amendment forms together with the relevant documentation should be submitted to the committee according to the European Commission’s Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human use. The application form and guidance notes may be accessed on:
In the light of the circumstances, notably the occurrence of any new event relating to the conduct of the trial or the development of the IMP where that new event is likely to affect the safety of the subjects, the sponsor and the investigator shall take appropriate urgent safety measures to protect the subjects against any immediate hazard. These safety measures may be taken without prior authorisation from the committee. The sponsor shall communicate to the committee the new events, the measures taken and their plan for future action as soon as possible. This should be by telephone in the first place followed by a written report. The written report should be submitted within eight (8) calendar days of the decision (except in the case were the urgent safety amendment involves the premature termination of a clinical trial, where notification should be made within fifteen (15) days). No fee will be attributable in this case.
If the committee is notified of any amendments that are relevant to the Medicines Authority only and these do not require assessment by the committee, no fee will be attributable to the committee.
Any other non-substantial amendments should be notified to the committee as soon as possible.
End of clinical trials
End of trial notifications should be made using the Declaration of the end of a clinical trial notification form.
The end of trial form together with any documentation, should be made according to the European Commission’s Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human use. The end of trial form and guidance notes may be accessed on:
Transitional arrangements
Clinical trials currently taking place which started before 1st May 2004 should be notified to the committee and they should comply with pharmacovigilance and good practice obligations.
Fees
Fees of clinical trials may be accessed on the website of the committee.
Reduced fees for clinical trial applications for academic research without financial support from industry may apply. The applications will be evaluated on a case by case basis and this concession will be at the discretion of the committee.
Appropriate proof of payment should always be attached with the application form. Payment of the relevant fee should be made at:
Bank Details:
Account Name:
Account Number:
IBAN:
Swift Code:
NB When effecting the payment the amount should be remitted in full, net of all bank charges.
Contact for further information
Applications and notifications should be submitted to:
Health Ethics Committee
Castellania Palace
15, Merchant's Street
Valletta VLT 03
Malta
Europe
Tel: (+00356) 25599000
Fax: (+00356) 25599385
Email:
B: Regulation of other clinical trials
Other clinical trials including those involving devices and interventions should also gain approval from the Health Ethics Committee before commencing. The application for such research should be picked up from the committee’s office (see ‘Contact for further information’). The documentation which is required to be handed in with these applications may be found in annex 12.
Amendments
Before a substantial amendment is implemented this should be authorised by the committee.
Substantial amendments are those amendments which are likely to have a significant impact on:
• the safety or physical or mental integrity of the subjects;
• the scientific value of the trial;
• the conduct or management of the trial; or, where applicable,
• the quality or safety of any device used in the trial.
In the light of the circumstances, notably the occurrence of any new event relating to the conduct of the trial where that new event is likely to affect the safety of the subjects, the sponsor and the investigator shall take appropriate urgent safety measures to protect the subjects against any immediate hazard. These safety measures may be taken without prior authorisation from the committee. The sponsor shall communicate to the committee the new events, the measures taken and their plan for future action as soon as possible. This should be by telephone in the first place followed by a written report. The written report should be submitted within eight (8) calendar days of the decision (except in the case were the urgent safety amendment involves the premature termination of a clinical trial, where notification should be made within fifteen (15) days). No fee will be attributable in this case.
Any other non-substantial amendments should be notified to the committee as soon as possible.
The notification of a substantial amendment should include the following information:
- covering letter, including reason for qualification as a substantial amendment;
- description of the amendment and reason/s;
- the new version of modified documents where the changes are so widespread and/or substantial that they justify a new version, identified with updated number of version and date. The changes should be clearly marked;
- supporting information including an updated overall risk benefit assessment, and where applicable, possible consequences for subjects already included in the trial and possible consequences for the evaluation of the results.
End of clinical trials
When a clinical trial finishes, this should be notified to the Health Ethics Committee as soon as possible.
Transitional arrangements
Clinical trials currently taking place should be notified to the committee and they should comply with pharmacovigilance and good practice obligations.
Appendices
Annex 1 Clinical Trials Regulations, 2004 (LN 490). Accessed on:
Annex 2 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Accessed on:
Annex 3 Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human use. Accessed on:
Annex 4 Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial. Accessed on:
Annex 5 Request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities and for opinion of the ethics committees in the community. Accessed on:
Annex 6 Request for authorisation of a substantial amendment to a clinical trial on a medicinal product for human use to the competent authorities and for opinion of the ethics committees in the community. Accessed on:
Annex 7 Declaration of the end of a clinical trial. Accessed on:
Annex 8 The check list of the information appended to the application (check list K).Accessed on:
Annex 9 Useful supporting documentation on the EudraCT database. Accessed on:
Annex 10 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use should be followed. Accessed on: Of particular relevance is the Note for guidance on good clinical practice (CPMP/ICH/135/95).
Annex 11 – documentation needed for clinical trials on investigational medicinal product:
The applicant should include one printed copy and one soft copy (on electronic storage media)of the following documents (if applicable) with the initial clinical trial application form. The documents of the printed copy should be submitted in the order given below. The soft copy should contain the following documents saved in the order shown below. This annex should also be filled in, printed, and submitted with the relevant documentation. An electronic copy of this annex should also be submitted after being completed.
Tick if Tick if not
supplied applicable
One printed copy of the documents described below
(including this annex after being completed)
Disk with one electronic copy of all documents listed below
(if applicable), including this annex after being completed
If you, or a related company (including companies from whom
you have acquired the rights to the product or active substance and
companies with whom you have a licence agreement), have made
any previous application to the Health Ethics Committee for a trial
involving the same active substance, including any application that
was previously not accepted, kindly state EudraCT number and
sponsor protocol number of the previous application(s)
EudraCT number(s):
Sponsor protocol number(s):
Bank receipt of payment (the clinical trial title and EudraCT
number should be written on it if the applicant applies for more
than one trial)
Receipt of confirmation of the EudraCT number i.e. a copy of the
email containing the notification of the EudraCT number which
was received by the applicant
Covering letter
Application form
Tick if Tick if not
supplied applicable
Module 2 of the Detailed guidance on the application format
and documentation to be submitted in an application for an Ethics
Committee opinion on the clinical trial on medicinal products for
human use
Disk with the file for EudraCT containing the exact information
contained on the printed CT application form handed to the
Health Ethics Committee. The file should be saved and named
with the EudraCT number of the clinical trial
List of competent authorities to which the application has been
submitted and details of decisions, if available
If the applicant is not the sponsor, a letter of authorisation
enabling the applicant to act on behalf of the sponsor (the
wording ‘to act on behalf of’ would signify signing /
communicating on behalf of the sponsor)
Subject related
Informed consent form
Subject information leaflet
Arrangements for recruitment of subjects
Protocol related
Protocol with all current amendments
Protocol summary in English
Peer review of the scientific value of the trial, when available,
not compulsory
Ethical assessment made by the principal / coordinating
investigator, if not given in the application form or protocol
Tick if Tick if not
supplied applicable
IMP related
Investigator’s brochure
Summary of Product Characteristics (for products with
marketing authorisation in the Community)
Outline of all active trials with the same IMP
Viral safety studies, if applicable
TSE Certificate when applicable
Examples of the label in English and/or Maltese
Facilities & staff related
Facilities for the trial
CV of the coordinating investigator in the MS concerned
(for multicentre trials)
CV of each investigator responsible for the conduct of the trial in
a site in the MS concerned (principal investigator)
Information about supporting staff in each site
Finance related
Provision for indemnity or compensation in the event of
injury or death attributable to the clinical trial
Any insurance or indemnity to cover the liability of the
investigator and sponsor
Compensation to investigators
Compensation to subjects
Agreement between the sponsor and the trial site
Agreement between the investigators and the trial sites
Certificate of agreement between sponsor and investigator when
not in the protocol
Tick if Tick if not
supplied applicable
Other
Informed consent letter of authorisation holder when
cross-referencing is made
Proof of establishment of the sponsor or its legal representative
in the Community
All available contact numbers - mobile, home, places of work
including clinics and private hospitals, fax of primary place of
work, pager - should be attached with the application. All local
investigators participating in the conduct of the research should
make themselves available and accessible to the Health Ethics
Committee
The intention of the sponsor on whether to continue to supply the
IMP or other therapies, for example, supportive therapy, after the
research ends together with the time periods and conditions
involved (if not already provided in the protocol).
Copy of the opinion of other ethics committees, if applicable
In this case, any differences between the documentation (including the version) submitted to the other ethics committees and to the Health Ethics Committee should be highlighted.
Letter signed by Head of department(s) / Consultant(s) concerned
when patients / relatives and / or records of their department are
involved.
Annex 12 - documentation needed for all other clinical trials:
The applicant should include one printed copy and one soft copy (on electronic storage media)of the following documents (if applicable) with the initial clinical trial application. The documents of the printed copy should be submitted in the order given below. The soft copy should contain the following documents saved in the order shown below. This annex should also be filled in, printed, and submitted with the relevant documentation. An electronic copy of this annex should also be submitted after being completed.
Tick if Tick if not
supplied applicable
One printed copy of the documents described below
(including this annex after being completed)
Disk with one electronic copy of all documents listed below
(if applicable), including this annex after being completed.
The disk should also contain the application containing the exact
information contained on the printed application form handed to
the Health Ethics Committee.
Bank receipt of payment (the Clinical Trial title should be written
on it)
Covering letter
Application form
Investigator’s brochure
List of other bodies to which the application has been
submitted and copy of opinion, if available
In this case, any differences between the documentation (including the version) submitted to the other bodies and to the Health Ethics Committee should be highlighted.
If the applicant is not the sponsor, a letter of authorisation
enabling the applicant to act on behalf of the sponsor (the
wording ‘to act on behalf of’ would signify signing /
communicating on behalf of the sponsor)
Examples of the label in English and/or Maltese
Tick if Tick if not
supplied applicable
Subject related
Informed consent form
Subject information leaflet
Arrangements for recruitment of subjects
Protocol related
Protocol with all current amendments
Protocol summary in English
Peer review of the scientific value of the trial, when available,
not compulsory
Facilities & staff related
Facilities for the trial
CV of the principal investigator
CV of the coordinating investigator in Malta
(for multicentre research studies)
Information about supporting staff in each site
Finance related
Provision for indemnity or compensation in the event of injury
or death attributable to the clinical trial
Any insurance or indemnity to cover the liability of the
investigator and sponsor
Compensation to subjects
Compensation to investigators