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Substantial & non-substantial amendments

Amendments are changes made to the research after a favourable ethical opinion has been given. They can be ‘substantial’ or ‘non-substantial’. 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:

  1. the safety or physical or mental integrity of the subjects of the trial;

  2. the scientific value of the trial;

  3. the conduct or management of the trial; or

  4. the quality or safety of any investigational medicinal product used in the trial.

Examples of substantial and non-substantial amendments

Substantial:

  • changes to the design or methodology of the study, or to background information affecting its scientific value;
  • changes to the procedures undertaken by participants;
    any change relating to 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 chief investigator or key collaborator;
  • a change to the insurance or indemnity arrangements for the study;
  • 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 REC application.

Some changes, however, will have no significant implications for participants or for the conduct, management or scientific value of the study and can be regarded as ‘non-substantial’ or ‘minor’ amendments.

 Non-Substantial:

  • 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 chief investigator’s research team (other than appointment of key collaborators);
  • changes to the research team at particular trial sites (other than appointment of a new principal investigator in a CTIMP);
  • 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;
  • inclusion of new sites and investigators in studies other than CTIMPs;
  • extension of the study beyond the period specified in the application form

Changes to contact details for the sponsor (or the sponsor’s representative), chief investigator or other study staff are minor amendments but should be notified to the main NHS REC for information. You should notify both the main NHS REC and the relevant local NHS REC if the principal investigator’s contact details have changed.

You must inform the main NHS REC of all substantial amendments by completing a notice of substantial amendment. Non-substantial amendments do not need to be notified. For further details please see NHS HRA: UK Process for Management of Amendments.