K3. Clinical trial agreements
When reviewing the clinical trial agreement, an accredited medical research ethics committee (MREC) and the CCMO will follow the CCMO Directive on the assessment of clinical trial agreements. The directive is applicable to research that falls under the scope of the WMO and when there is a written agreement between the parties involved in the financing, set up and execution of the research.
Review of the clinical trial agreement
The review of the clinical trial agreement is limited to the following two aspects, on the basis of the CCMO Directive on the assessment of clinical trial agreements:
- The provisions with regards to premature termination of the scientific research or the agreement;
- The provisions with regards to the publication of the study results of the scientific research.
Please note that similar provisions in the research protocol will also be assessed by the review committee (accredited MREC or CCMO).
To prepare the clinical trial agreement you may use the templates written by a collaboration of parties united in the Dutch Clinical Research Foundation (DCRF). The parties involved are the Cooperating Top Clinical Training Hospitals (STZ), the Netherlands Federation of University Medical Centers (NFU), the Association Innovative Medicines, Foundation the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital (NKI/AvL) and the Association of Contract Research Organisations in the Netherlands (ACRON).
Clinical trial agreement for use with VGO
If you submit a Site Suitability Declaration (Verklaring Geschiktheid Onderzoeksinstelling, VGO) as a declaration for the local feasibility of the study, you also need to submit a clinical trial agreement in accordance with the VGO procedure for local feasibility. Use of the VGO will become obligatory for all new research with a medicinal product as of 1 November 2021.
This standard agreement contains a paragraph stating that if the agreement is signed by the executive board/management before the review committee has approved the research, the executive board/management gives the researcher permission, subject to conditions precedent, to conduct the research in the centre.
Clinical trial agreement for use with Research Declaration
If you submit a Research Declaration as a declaration for the local feasibility of the study, you also need to submit a clinical trial agreement in accordance with the Research Declaration procedure for local feasibility. As of 1 November 2021, use of the Research Declaration will no longer be possible for new research with a medicinal product. For these studies you are required to submit a VGO and the corresponding clinical trial agreement.
The CCMO considers the clauses regarding premature termination of the study and regarding publication in these models to be in line with the CCMO Directive on the assessment of clinical trial agreements.
Submitting the clinical trial agreement
If there is a clinical trial agreement, this agreement is part of the primary submission of the research file to the review committee (accredited MREC or CCMO). The sponsor of the research may submit an unsigned version initially. The submitted clinical trial agreement must have a reference and version number.
If the sponsor has submitted an unsigned version, at the initial application, the sponsor must submit a signed clinical trial agreement to the review committee before the start of the study. In the accompanying cover letter you need to state whether the provisions assessed by the review committee, have been altered in the signed research contract. This is based on the principle that the signed version must be the same version as the one approved by the review committee.
A change concerning the two aspects of the clinical trial agreement that are reviewed by the review committee – criteria for early termination and publication of study results – is considered to be a substantial amendment and will be assessed again by the review committee. You need to state clearly in the accompanying cover letter what alterations have been made. Here too, a signed clinical trial agreement must be submitted to the review committee for information purposes after approval of the amendment has been obtained. For further reading on this, see the procedure for initial assessment as described above. Adequate version control and an accurate description of the alterations made in the various versions is of the utmost importance to obtain a prompt settlement from the review committee.
If there is no clinical trial agreement, this must be stated in the cover letter. Without such a statement, the review committee will assume that a clinical trial agreement is part of the research file. If the clinical trial agreement is absent the review committee will consider the research file to be incomplete.
In the case of multicenter research, if clinical trial agreements have been reached, at least one clinical trial agreement is required for the review of the research file. This is the reference clinical trial agreement. A written statement by the sponsor is sufficient for the other Dutch centers. In the statement it must be stated that the clinical trial agreements for the other centers are similar to the reference clinical trial agreement concerning the two aspects reviewed by the review committee. If such a statement is not included, then the clinical trial agreements of all participating centers must be submitted.