A substantial amendment is defined as an amendment to the terms of the application, or to the protocol or any other supporting documentation, that is likely to affect to a significant degree:
- the safety or physical or mental integrity of the subjects of the study;
- the scientific value of the study;
- the conduct or management of the study; or
- the quality or safety of any investigational medicinal product used in the trial.
For all studies, it is the responsibility of the sponsor to determine whether an amendment is substantial.
Examples of substantial and non-substantial amendments are available in the Resources.
Some review bodies only need to review substantial amendments. Other review bodies will have different criteria for changes that are relevant to their remit. Please refer to guidance provided about which review bodies need to be notified of amendments.