During the study, new information may become available or changes may be made to documents in the study file (e.g. the protocol or the PIF) that have already been approved by the MREC. Any new documents or changes must be reported and, if substantial, reviewed again by the committee (MREC or CCMO).
Changes are deemed substantial if they are related to:
- The safety or the physical or mental integrity of the subjects
- The scientific value, set-up or management of the study
- The quality or safety of the investigational medicinal product or other research products
Examples of a substantial amendment include a new participating centre, additional blood samples, change of principal investigator or independent expert, new versions of an Investigator’s Brochure or IMPD, changes in the inclusion and exclusion criteria and additional study activities.
In the case of a substantial amendment, the amended documents must be submitted to the assessment committee (or the competent authority as well), as described on the website of the MREC Amsterdam UMC and the CCMO.
Non-substantial amendments need not be assessed or approved. When acting as the reviewing MREC, the MREC will ask to receive any non-substantial amendments for information purposes). When acting as the reviewing MREC, the competent authority need not receive the non-substantial amendments.
Examples of non-substantial amendments include minor changes in subject information that have no effect on the set-up or implementation of the study.
Information on reporting substantial amendments is available on the website of MREC Amsterdam UMC.
For medical-device trials that have been reported to the competent authority (the CCMO), there is no obligation to submit amendments to the competent authority, with the exception of amendments relating to the addition of an institution. In that case, the competent authority should receive the consent of the Executive Board. For more information see the website of the CCMO.
Substantial amendments to drug trials always require the submission via CTIS. See the site of the CMC for further information.