Plans for communicating significant protocol amendments to relevant parties (e.g., trial participants, ethical committees) {25}
After the protocol has been submitted to the ethics committee (EC), any substantial change will require a formal amendment. The amendment must be signed by all of the signatories to the original protocol. Once the study has started, amendments should be made only in exceptional cases. The ethics committees must be informed of all amendments. Approval must be sought for ethical aspects and obtained from the competent authorities