Guide to Substantial Amendments
An amendment is generally considered to be any change made to the study that impacts the ethics review application, the protocol or any other supporting documentation after the study has been approved by the Research Ethics Committee and the study has started.
A substantial amendment or substantial ‘modification’ is a change to the research study that is likely to have a significant effect on any of the following:
- The safety, health, rights, physical or mental integrity of the subjects of the study;
- The scientific value of the study, or the robustness or reliability of the data generated by the study;
- The conduct or management of the study; or
- The quality or safety of any investigational medicinal product or device used in the study.
A non-substantial amendment is any change to the research study in terms of the REC application, the protocol or any other supporting documentation that does not meet the definition of a substantial amendment.
Once a study has begun, the Principal Investigator or Sponsor may wish to make amendments to the study protocol. The Principal Investigator or Sponsor may make an amendment to a study protocol, other than a substantial amendment, at any time.
NREC review process for amendments
Substantial amendments must be reviewed and approved by the appropriate NREC before they are carried out.
Non-substantial amendments do not need to be reviewed by the NREC, but applicants may need to notify the National Office of some non-substantial changes or modifications such as change in contact points etc, or other material information coming to pass after the study has started.
It is up to the Principal Investigator or a Sponsor to determine whether an amendment should be considered ‘substantial’ or ‘non-substantial’.
Below are some examples of study changes that would be considered substantial or non-substantial amendments.
Examples of substantial amendments:
- changes to the design or methodology of the study, or to background information likely to have a significant impact on its scientific value;
- changes to the procedures undertaken by study participants;
- changes likely to have a significant impact on the safety or physical or mental integrity of participants, or to the risk/benefit assessment for the study;
- significant changes to study documentation such as participant information sheets, consent forms, questionnaires, letters of invitation, letters to GPs or other clinicians, information sheets for relatives or carers;
- a change of sponsor(s) or sponsor’s legal representative;
- appointment of a new study lead Principal Investigator;
- a change to the insurance or indemnity arrangements for the study;
- inclusion of a new study site (not listed in the original application);
- appointment of a new Principal Investigator at a study site in a CTIMP;
- temporary halt of a study to protect participants from harm, and the planned restart of a study following a temporary halt;
- a change to the definition of the end of the study;
- any other significant change to the protocol or the terms of the NREC application.
Examples of non-substantial amendments:
- minor changes to the protocol or other study documentation, e.g. correcting errors, updating contact points, minor clarifications;
- updates of the investigator’s brochure (unless there is a change to the risk/benefit assessment for the trial);
- changes to the Principal Investigator’s research team
- changes to the research team at particular trial sites;
- changes in funding arrangements;
- changes in the documentation used by the research team for recording study data;
- changes in the logistical arrangements for storing or transporting samples;
- extension of the study beyond the period specified in the application form.
(Source: some of the content has been adapted from the Health Research Authority’s website.)