The transition period from the Directive to the EU Regulation on Clinical Trials of Medicinal Products (CTR) has ended on 30 January 2025. From 31 January 2025, all trials with medicinal products that have at least one active trial site in Denmark must therefore be transferred to CTR.
Changes to trials transferred from the Directive, including updating the application dossier in accordance with the requirements of the EU Regulation.
Upon submission of the first Substantial Modification (SM) application after the clinical trial has been transferred to CTR:
Part I:
All Part I documents of the trial must be updated to meet the requirements for CTR. The sponsor can wait to submit the first SM for Part I until there are plans for the Part I dossier, however, all Part I documents must be updated before applying for the addition of new member countries to the trial. See also CTCG Best Practice below.
Part II in Denmark:
Sponsor does not have to submit the SM to Part II in Denmark for transition trials, unless significant changes are made to the trial that deal with the Part II dossier.
For the first SM application for a transition trial involving Part II, the relevant documents in the Part II dossier must be updated in accordance with the rules under the CTR. For transition attempts in Denmark, only updating and submitting documents is required for the Part II aspects that are affected by the significant changes in the SM application.
- For example, if the amendment concerns the addition of a new trial site in Denmark, documents must only be submitted for this new trial site and its associated investigator.
- 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.
- For example, if the change concerns the addition of (new) recruitment material (e.g. a poster or pamphlet), only the new recruitment material and an updated version of the document about the recruitment process must be submitted.
- For example, if the change relates to a revised experimental budget, only the updated budget and an updated version of the funding document must be submitted.
Other documents under Part II (which are not affected by the requested changes) can be left as submitted during the transition application, including "placeholder documents".
In Denmark, the sponsor does not have to complete the Part II dossier, including completing and submitting all European CTR templates at the first SM to Part II after transition.
If the Danish Appendix to the Protocol has not already been submitted with the transition application, applicants with multinational trials are encouraged to submit the currently approved version of this document (for example, under the Part II section of CTIS that is updated in the SM application). The Danish appendix to the protocol is helpful for the MREC’s assessment of the significant changes in the SM application, compared to what has previously been approved under the Directive.
The first time an SM application concerns participant information and/or consent form after transfer to the EU Regulation, MREC requires the following updates:
- The EU trial number (20xx-xxxxxx-xx(-xx)) and the original English title of the clinical trial shall be added/updated in the participant information and consent form in accordance with CTR, Article 29(2)(e)
- It should be added/updated in the participant information that a summary of the study results will be made available on the EU portal (euclinicaltrials.eu) and that the summary can be found by searching for the EU trial number.
- Please note that it should no longer be stated that results are published and can be found on eu.trialregister.eu.
- The period for archiving data shall be changed to 25 years after the end of the trial, cf. CTR, Article 58.
- The name of the approving research ethics committee must be addressed to "The Medical Research Ethics Committees (MREC)" in the participant information, if it was not the MREC that approved the trial under the Directive.
- The correct version of the booklet "Your rights as a participant in a clinical trial with medical products" must be submitted and properly referenced in the participant information. The correct version of the pamphlet can be found here. The booklet "Participant's Rights in a Health Science Research Project" and the brochure "Before You Decide" are not valid for clinical trials under CTR and must be removed from the participant information and CTIS.
- If minor participants under the age of 15 are included in the study, age-appropriate information material must be submitted to this(these) group(s) of trial participants, cf. Executive Order on Clinical Trials of Medicinal Products, section 3(3), (4).
A number of guidelines have been prepared for use in applications for SM for transition attempts. Please note, however, the special requirements for updating the Part II dossier for trials in Denmark, as described above.
Further information about transition attempts
Read here about clinical trials under the Directive that are not transferred to CTR.