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.

For clinical trials submitted via CTIS according to the rules of the CTR, the ABR form and EudraCT form expire. For currently ongoing clinical trials, the ABR form and EudraCT form will continue to exist as long as these studies have not been transferred to CTIS. See our website for more information about the transition period.

For studies submitted in EudraCT, and not yet transferred to CTIS, a Frequently Asked Questions document is available. It also contains information about the transition to CTIS as of 31 January 2025. See the frequently asked questions about EudraCT on the European Medicines Agency website.

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 the CV may be submitted without a signature in CTIS. This does not apply to the Site Suitability Declaration (Verklaring Geschiktheid Onderzoeksinstelling, VGO). A validated digital signature is accepted for this document. 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).

In October 2023 EMA published revised transparency rules for CTIS (see: Transparency rules: general information). Based on these revised transparency rules, CV and VGO will not be published in the public portal of CTIS. As long as the revised rules are not technically implemented in CTIS, the sponsor is allowed to upload a document in the slot “for publication” with the text “The present document is no longer subject to publication in line with revised CTIS transparency rules. Further information is provided in section 4 of the ‘Q&A on the protection of Commercially Confidential Information and Personal Data while using CTIS’ published on the ACT EU website – Implementation of the Clinical Trials Regulation” (see also annex I of the Q&A on the revised transparency rules in CTIS). In the slot “not for publication”, the sponsor shall upload the documents with signatures.

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. Validated standard questionnaires, such as the quality of life questionnaire SF36, do not need to be included. 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.

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.

No, the marginal review by the competent authority (CCMO or Ministry of Health, Welfare and Sport) shall be repealed for clinical trials submitted in CTIS.

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. If a sponsor does not have the possibility to report SUSARs in Eudravigilance due to a lack of resources, the CCMO can be contacted. The annual safety report (ASR/DSUR) must be submitted in CTIS.

For CTD clinical trials all SUSARs must also be reported via Eudravigilance. If a sponsor does not have the possibility to report SUSARs via Eudraviglance, he can report this in the SUSAR module of ToetsingOnline. The competent authority will report SUSARs occurring in the Netherlands in Eudraviglance. In addition, the obligation to report all SUSARs to the MREC remains. SUSARs no longer need to be reported to the competent authority. However, the annual safety report (ASR/DSUR) has to be submitted to the MREC and to the competent authority.

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.

All relevant information on so-called ‘transition trials’, clinical trials authorised under the Clinical Trials Directive (CTD) that need to be transitioned to the Clinical Trials Regulation (CTR), can be found on the following CCMO webpage: Transition trials: CTD to CTR.

The CTIS public portal is not (yet) a WHO primary registry. However, it does meet the requirements for prospective registration set by the International Committee of Medical Journal Editors (ICMJE) for publication in scientific journals.

Currently, CTIS is an official data provider to the International Clinical Trial Registry Platform (ICTRP) of the World Health Organization (WHO). It is EMA’s intention that the CTIS public portal will be a WHO registry, but this application is not yet finalized. 
 

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