Amendments

  • WMO

During the study, new information may become available, or changes may be made to previously approved study documents (e.g. the research protocol or the subject information letter). Any new documents or modifications must be reported and, if deemed substantial, assessed again by the review committee (MREC or CCMO) through the submission of an amendment..

Substantial amendments

A modification is considered substantial if it affects:

  • The safety, health (physical/mental integrity) or rights of participants;
  • The scientific value, design, or management of the study;
  • The robustness or reliability of the generated research data;
  • The quality or safety of the investigational medicinal product or other research products.

Examples of a substantial amendment include:

  • A new participating centre;
  • Additional study procedures, such as an additional blood sample;
  • Change of principal investigator or independent expert;
  • New version of the Investigator's Brochure (IB) or Investigational Medicinal Product/Device Dossier (IMPD/IMDD);
  • Changes to the in- or exclusion criteria.

However, for clinical investigations involving a medical device the following applies: if the substantial modification leads to a change in the legal framework of the study, a new research file must be prepared and submitted to the review committee. This is the case when, for instance:  

  • a study that was previously approved under the Medical Device Directive (MDD) replaces the medical device under investigation. Then, the MDR will apply;
  • an Article 82 study changes into an Article 62 study.

    Non-substantial amendments

    Non-substantial amendments do not require review or approval. However, the review committee takes note of minor modifications for information purposes.

    Examples of non-substantial amendments include:

    • Textual corrections;
    • Modifications that do not affect the study's design or implementation.

    Submission to the review committee

    The CCMO website provides comprehensive information on amendments for each study type: medicinal products, medical devices, IVDs and other studies subject to the WMO.

    Amendments for clinical trials involving medicinal products require submission via CTIS. For further details, refer to the CMC website.  

    For other research subject to the WMO, MDR or IVDR, amendments must be submitted to the review committee via the Research Portal. Consult the MREC website for local procedures and the CCMO website for guidance on using the Research Portal.

    Neither substantial nor non-substantial amendments need to be submitted to the CCMO as the competent authority.