Questions and answers CTR – The Netherlands

For questions about the assessment of clinical trials with medicinal products in the Netherlands, please email: ctr@ccmo.nl.

In that case, you may contact the representative for clinical trials in the relevant UMC. The email addresses for questions on clinical trials with medicinal products of the seven UMCs in the Netherlands are listed below.

It is not necessary to ask informed consent for this again. Participants that are still in the trial could for instance be informed about this upon the next update of the ICF. It can also be communicated in different ways, such as verbally or via a website, there are no guidelines for this.

For new clinical trials submitted via CTIS, there is no ABR form or EudraCT form. For transition trials authorised under the Clinical Trial Directive and transitioned to CTIS, the ABR and EudraCT forms are not part anymore of the CTIS application.

No, the CTR does not provide for this. In order to be able to continue to ensure that the agreements with regard to the publication and termination of the clinical trial are in accordance with the Richtlijn Beoordeling Onderzoekscontracten (CCMO Directive on the assessment of clinical trial agreements), questions on these two matters have been included in the form 'Compensation for trial participants, investigator, funding clinical trial and other arrangements' (research dossier Part II). This form can be found on Financial and other arrangements.

No, an independent expert is no longer required under the CTR.

The CCMO templates are mandatory, with the exception of the template CV of the investigator.

In the Netherlands, a signature is required for the Site Suitability Declaration (Verklaring Geschiktheid Onderzoeksinstelling, VGO) submitted in CTIS. A validated digital signature is also accepted for this document. A signature is not required for the CV of the principal investigator, preferrably a CV without signature is submitted. A signature is considered personal data. Any document with a signature and to be published based on the transparency rules for CTIS should be redacted (see: Redacted and unredacted documents).

On 18 June 2024 revised transparency rules were published for CTIS (see: Transparency rules: general information). Based on these revised transparency rules, CV and VGO are no longer published in the public portal of CTIS.

Documents, such as questionnaires and diaries, used to record study endpoints must be described in the study protocol and can be added as annexes to the protocol. They can also be submitted as separated documents in the Protocol section in CTIS (document code D4). See also the page on the protocol.

For clinical trials submitted before 1 November 2021, the Research Declaration (Onderzoeksverklaring) can be used for the new sites. The use of the Site Suitability Declaration (Verklaring Geschiktheid Onderzoeksinstelling, VGO) is voluntary for studies submitted before 1 November 2021.

No, it is enough to mention the EU Clinical Trial number without the last two digits in the documents. The last two digits refer to whether it concerns a first submission (EU clinical trial number ends with -00) or a re-submission of the same dossier (EU clinical trial number ends with -01 or higher). By leaving these last two digits out in the documents, the EU clinical trial number in the documents do not have to be changed when re-submission is required.

No, this is not allowed. Only the centers for which the set of documents is complete should be submitted in CTIS. This means a signed VGO, a CV and a declaration of interests of the principal investigator.

Each affiliate must be registered separately in the OMS system and receives an unique ID. The OMS distinguishes between Organization IDs and Location IDs, where Organizations are country specific and locations under an Organization are located in that same country. For each country you create an Organization with Location (s). For more information, see the document on EMA's website.

The organizations that need to be registered in OMS to be available for CTIS are sponsors or co-sponsors, third party contractors (e.g. CRO), EEA trial sites, and Marketing Authorisation Holders.

The EudraVigilance product database (XEVPMD) applies to medicines authorised in the EU (AMPs) and to IMPs used in clinical trials. The active substances have to be registered as well. See also paragraph 5 (Product management in CTIS) of the Sponsor Handbook. See for more detailed information the document on EMA's website.

No. The addition of a new participating center is a substantial amendment (of Part II). A substantial part II amendment can only be submitted in a Member State if:

• the Member State concerned has issued a positive decision on the clinical trial, and
• no other substantial amendment to the same clinical trial is being assessed in the Member State concerned.

For more information on substantial modifications, see Submission of a substantial modification.

A temporary replacement of a principal investigator (PI) should be reported as a Substantial Modification on Part II, containing the CV and Declaration of Interest (DoI) of the temporary PI. The details of the original PI should be maintained in the Trial Sites section in CTIS, and their CV and DoI should not be deleted. This way, no changes in CTIS are required when the PI returns. It is not necessary to report the return of the PI, it is sufficient to mention this in the cover letter of the next Substantial Modification. 

No, this requirement does not exist anymore for clinical trials under the CTR.

For CTR clinical trials all SUSARs must be reported via EudraVigilance. This means that every sponsor of a clinical trial must have access to EudraVigilance or must apply to the EMA for such an access. The annual safety report (ASR/DSUR) must be submitted in CTIS.

This is the same as under the old legislation (Directive 2001/20/EC (CTD)). The investigator must report the SAE to the sponsor within 24 hours of it being discovered. The protocol defines the type of SAE that does not require immediate notification. The sponsor shall include an aggregated table of SAEs in the Annual Safety Report (ASR) to be submitted in CTIS. Individual SAEs are not reported in CTIS. If a SAE is suspected to be related to the IMP and is not described in the Reference Safety Information, the SAE should be reported as a SUSAR. SUSARs must be submitted via Eudravigilance.

No, SUSARs always have to be submitted to Eudravigilance.

Yes, the CTIS public portal is a WHO primary registry that meets the requirements for prospective registration set by the International Committee of Medical Journal Editors (ICMJE) for publication in scientific journals.
 

No, CTIS is specifically for the submission and assessment of clinical trials conducted in the European Union.