The definition of a participating centre is:
‘The Dutch (research) institution where or from where one or more procedures are carried out on human research subjects for the sake of the study, insofar the subjects are required to undergo procedures or changes to behaviour is part of these procedures; a participating centre is the practice where one or more professionals in individual health care practice their profession.’
As of the 1st of March 2012 the CCMO External Review Directive 2012 (RET 2012) was enforced; it was changed as of the 1st of July 2015 (in Dutch). The RET 2012 applies to all multicentre research that falls under the Medical Research Involving Human Subjects Act (WMO), irregardless of whether it is research with a medicinal product.
The essence of the RET 2012 is the research declaration (version in force until 1-7-2015 and version in force from 1-7-2015) of the participating centre, which is issued by the head of the department, the care group manager or a person in a similar position. The local feasibility declaration which used to be signed by the management of the institution has been scrapped from the RET 2012. However, the board still has to give permission for execution of the study in its own institution after the reviewing MREC has approved the study. Only after permission from the board can a research commence in the centre concerned.
In the multicentre procedure no role has been created for the local (medical ethical) committees of the local participating centres. Therefore, an MREC of a participating centre may not again review a protocol after it has already been reviewed by another MREC. So in the case of multicentre research (and external monocentre research), MRECs of participating centres may not carry out a WMO review.
The boards of directors of the UMCs and STZ hospitals subscribe to the Guideline External Review 2012. This means that they respect the decision of the accredited MREC and that there will not be a double review of a research file. The boards of directors have made this known by signing the institution declaration (in Dutch). In doing so, the boards of directors of all these Dutch institutions ensure that the research file including the information for the participant of a study in their own institutions will not be again reviewed by their own local reviewing committee. Investigators can be assured that participation in multicentre research in these institutions is efficiently organised.
The research file containing the research declaration(s) is processed by an accredited MREC. You are required to submit the research declaration(s) of participating centres within 14 days of the initial submission of the research file. The reviewing committee is not obliged to include research declarations received after this deadline in the primary review. The MREC can process these declarations after they have issued the primary decision. It is therefore advised to include as many research declarations as possible in the research file before you submit the initial submission for review to the reviewing committee.
The majority of the MRECs review multicentre research for all of the institutions in the Netherlands; however a number of MRECs cover a limited region in the case of multicentre research.
In the ABR form you can include all the centres where the research will in all probability be carried out, even if the research declarations are missing from any of the centres given in this list. With regards to research with a medicinal product you can fill in the same participating centres as given in the EudraCT form. Research declarations which are made available after the issuance of the primary decision by the reviewing committee do not have to be sent to the competent authority.
Clinical Trial Agreement(s)
If clinical trial agreements are reached in the context of execution of multicentre research, the following applies to the submission of clinical trial agreement(s) in the medical/ethical review of multicentre research:
- there is at least one clinical trial agreement needed per participating centre. This is the reference clinical trial agreement.
- for all other centres a declaration by the sponsor will suffice. This must include text stating that the clinical trial agreements from the other centres are similar to the reference clinical trial agreement which has been reviewed by the MREC on the basis of the two aspects of the CCMO guideline review clinical trial agreements (premature termination research + publication research results).
Are both the reference clinical trial agreement and the declaration present? Then submission of the remaining clinical trial agreements of the study concerned to the reviewing committee (MREC or CCMO) is not necessary. Without the reference clinical trial agreement all agreements from the participating centres must be sent with the documents as appendices to the clinical trial agreement. The same applies to when the declaration is missing.