K3. Clinical trial agreements
For the assessment of clinical trial agreements (CTAs) by the acknowledged medical research ethics committees (MRECs) and CCMO, the revised CCMO Directive on the assessment of clinical trial agreements is followed. The guideline applies to research that falls within the scope of the WMO and involves a written agreement between the parties involved in financing, designing or conducting the trial.
CTA assessment
Based on the CCMO guideline Assessment of research contracts, the assessment of the CTA is limited to two aspects:
- The provisions in the CTA regarding early termination of the medical study or agreement;
- The provisions in the CTA regarding the publication of the results of the medical study.
The ethics committee (acknowledged MREC or CCMO) incidentally also assesses similar provisions in the research protocol.
CTA template
To speed up the submission process, you are strongly advised to use the (unmodified) CTA template. This template was developed and agreed upon by a collaboration of parties united in the Dutch Clinical Research Foundation (DCRF).The parties involved are:
- Collaborating Top Clinical Teaching Hospitals (STZ),
- Dutch Federation of University Medical Centres (NFU),
- the Innovative Medicines Association (VIG),
- Foundation the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI/AvL),
- Association of Contract Research Organisations in the Netherlands (ACRON),
- Princess Máxima Centre for Paediatric Oncology (Máxima).
If, in exceptional cases, an adaptation of the CTA template is nevertheless necessary, the deviation from a clause is preferably recorded in an annex.
CCMO is of the opinion that the clauses in this CTA template concerning the premature termination of research and the disclosure of research results are in line with CCMO guideline Assessment of Research Contracts.
Site Suitability Declaration (VGO)
From 1 November 2021, use of a Site Suitability Declaration(VGO) is mandatory for new studies with a medicinal product. The CTA template includes a paragraph describing that if the contract is signed by the board of directors/directorate before the review committee has approved the study, the board of directors/directorate authorises the investigator, under conditions precedent, to conduct the study at the institution.
CTA template for industry-sponsored research
A new CTA template for industry-sponsored research has been in use as of 14 February 2024.
The CTA template for industry-sponsored research has two versions:
- Version A for agreements between sponsor and participating centre;
- Version B when the CRO is involved as a party to fulfil financial obligations to the participating centre and/or the principal investigator.
Note! If this template is used for research other than research with a medicinal product (i.e. research falling within the scope of the WMO, MDR, IVDR, Embryo Act), provisions 21.2 and 21.3 do not apply.
A guidance to the templates is also available.
CTA template investigator-initiated research not modified
No new version is yet available for investigator-initiated research (it is still under development). Currently, of this contract type, a choice can be made between a contract template for use with VGO and a contract template for use with a Research Declaration As indicated above, use of the VGO is only mandatory for studies with a medicinal product.
CTA template non-WMO research
A CTA template developed by the DCRF for non-WMO research is also available.
CTA submission
If a CTA is part of the research file, you should have submitted it at the start of the assessment by the assessing ethics committee (accredited METC or CCMO). The sponsor of the research may decide whether to submit a signed version immediately at that time or initially only an unsigned version. The CTA you submit must always bear an attribute with version number.
If the sponsor submits an unsigned version at the start of the review, the sponsor must still submit a signed CTA to the review committee for notification before the review starts. In the accompanying offer letter, you should indicate whether or not the provisions reviewed by the ethics committee have been amended in the signed CTA. The starting point is that the signed version is the same version already approved by the ethics committee.
An amendment concerning the two aspects in the CTA on which the ethics committee adjudicates - criteria early termination and disclosure of study results - is considered a substantial amendment and will have to be reviewed again by the ethics committee. In the accompanying offer letter, you should clearly indicate what the amendments are. Again, after approval of the CTA amendment, a signed CTA must be submitted to the ethics committee for notification. Otherwise, see the procedure described above for the initial review. Adequate version management and a description of the amendments in the various versions are important for quick handling by the review committee.
If no CTA has been concluded, you should mention this in the offer letter accompanying the research file. Without such a passage in the offer letter, the assessing review committee will have to assume that a CTA is part of the research file. In the absence of the CTA, it will have to consider the research file incomplete.
Multicentre studies
In multicentre studies, if CTAs are concluded, at least one CTA is required for case review. This is the reference CTA. For other Dutch centres, a written statement from the sponsor/provider is sufficient. This must state that the CTAs of the other centres are identical to the reference CTA with regard to the two components assessed by the ethics committee. In the absence of such a statement, you must submit the CTAs of all participating centres.