Guidance for submission of transition trials

Ongoing trials authorised under the Directive that have active sites on 30 January 2025 must be transferred to the EU Clinical Trial Regulation (CTR). If the transfer is not approved by 30 January 2025, the trial must be stopped, otherwise it will be conducted illegally. The Sponsor/Investigator is therefore encouraged to familiarise themselves with the information below and plan and prioritise in good time whether there are ongoing trials approved under the Directive that must be transferred to the CTR.

Which trials should be transferred to the CTR?

An active site means that there has not been a Last Patient/Last Visit (LPLV) and that trial-specific activities with trial subjects are still ongoing at the site. In the case of a multinational trial where there are no longer active sites in Denmark, cf. the above, but which is still ongoing in other member states, the trial must only be transferred to the CTR in these countries. In the case of a mononational trial where the Danish Medicines Agency has received a notification of trial termination (LPLV), the trial does not need to be transferred to the CTR.

Before the trial is transferred

All applications for substantial amendments (protocol amendments) for trials under the Directive must be finalised before transfer. Remember to take into account the processing time at the Danish Medicines Agency and the Scientific Ethics Committees (SEC). If the submission is clearly marked "Preparing for transition", both authorities will try to prioritise fast processing.

For multinational trials, ensure that all documents in Part I of the application are harmonised or consolidated. This means that the protocol must be the same in all member states, or any national differences must be included in the protocol (as a single document). In addition, the Investigator's Brochure and Investigational Medicinal Product Dossier may need to be harmonised or consolidated before transfer. See CTCG best practice below.

If harmonisation or consolidation results in significant changes to the documentation, these must be approved as substantial amendments (protocol amendments) prior to transfer. Remember to take into account the processing time at the Danish Medicines Agency and VMK. If the submission is clearly marked "Preparing for transition", both authorities will try to prioritise fast processing.

If the changes are not significant, it must be made clear in the cover letter when submitting the application for transfer. The cover letter must also state which versions of the documents have previously been approved under the Directive, as well as the approval date for these and which Scientific Ethical Committee has approved the trial under the Directive. VMK recommends using the template for the cover letter prepared by CTCG, see below.

Application for transfer to the EU Regulation

It has been agreed between the EU member states that the actual processing of "transitioning applications" is shortened to one week after the application has been declared valid - typically about 32 days from submission, as the application must first be validated. However, reservations are made for longer processing times in the event of major deficiencies in the submitted material in Part II. The assessment is solely an administrative process, and no new scientific ethical assessment of the trial is carried out. Please note that the application must be approved and not just submitted by 30 January 2025.

Practical guidance for Part II of the transition application

VMK generally follows the guidance on the European Commission's Eudralex Volume 10: Guidance for the transition of clinical trials (https://health.ec.europa.eu/document/download/10c83e6b-2587-420d-9204-d49c2f75f476_en?filename=transition_ct_dir-reg_guidance_en.pdf)

The cover letter

The cover letter must contain information about:

  • The name of the ethics committee that authorised the original trial application. This can be a regional scientific ethics committee (which must be stated by name), the Scientific Ethical Medical Committees (SMC) or the National Scientific Ethics Committee (NSC).
  • That all documents submitted in the CTIS portal under Part II for Denmark are the documents currently approved by the relevant scientific ethics committee. It is recommended to use the template for the cover letter prepared by CTCG, see link under further information.

Part II documents

The only mandatory documents for Part II of the application are the currently approved versions of the participant information(s) and consent form(s).

For the mandatory sections in the CTIS portal "Recruitment arrangements", "Financial arrangements" and "Proof of insurance", we recommend uploading a so-called placeholder document, which contains a description/confirmation that this aspect has been assessed and approved by the ethics committee that has assessed the trial under the Directive (and therefore included in the authorisation under the Directive).

For multinational trials, we also encourage the applicant to upload the currently approved version of the Danish Appendix to the protocol (for example under "Proof of insurance"). This document should contain the country-specific information authorised under the Directive for the sections "Recruitment arrangements", "Financial arrangements" and "Proof of insurance".

There is no requirement to submit additional documentation in Part II and the other fields in the CTIS portal can therefore be left blank. If the applicant wishes to submit additional documentation in connection with the transition application, please note that only documents authorised under the Directive will be accepted. We recommend that additional documentation is clearly indicated in the cover letter, as per the template provided by CTCG.

The applicant must inform the original committee that authorised the trial under the Directive's rules that the clinical trial has been transferred to the CTIS and will therefore be regulated by the CTR rules going forward.

Trials in emergency situations

For clinical trials in emergency situations, the rules under the CTR differ significantly from the rules under the Directive in Denmark, including the requirements for recruitment and obtaining informed consent. Therefore, submission of a substantial modification is required to fulfil the conditions in article 35 of the CTR (clinical trials in emergency situations) immediately after the transition application is approved. The applicant will be asked in the processing of the transition application to confirm that such an amendment request is planned.

Practical guidance on the first substantial modification for the transition attempt / dossier completion in Part II of the application

For the first substantial modification to a bridging trial covering Part II of the application, relevant documents in Part II must be updated according to the rules under the CTR. For transition trials processed in Denmark, only the documents affected by the substantial modification need to be submitted and updated. For example, if the change involves the addition of a new trial site in Denmark, only documents for this new trial site and its corresponding study director/investigator need to be submitted. For example, if the amendment concerns a new analysis of biological material, only an updated version of the biological material document and the updated participant information must be submitted.

Additional information

A number of guidelines have been prepared for use in applications for transfer to the EU Regulation:

 

Last updated 01-02-2024

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