How to submit study amendments

You may find that a lot of the work listed in these pages has already been going on in parallel to getting R&D Approval.  As the PI for the study you are responsible for making sure all the things listed below have been completed before patients are recruited to the study.  However, you can delegate these tasks to the relevant research nurse or other member of staff working on the study.

If you are a Nurse, Research Fellow or other member of staff working with the PI on a study you should support the PI to ensure the work listed below is completed and kept up-to-date.

Prepare the Local Paperwork for Study Startup

The trial documentation such as patient Information sheets (PIS’s) and consent forms (CF’s), GP letter templates or other trial related paperwork that needs to have local contact details added and be put on local headed paperwork should have been created ready to be added to the Site Specific assessment ( SSI) application.

If the study is commercial, then the likelihood of the sponsor company providing a site study file is probable, however, if your study is academic then it will be your responsibility to create a site file from scratch using either an National Institute of Health Research (NIHR) template or one that can be provided by the R&D office. These site file contents list are generic so not all sections may apply to your study the templates can be adapted as required.

Substantial Amendments

A substantial amendment is defined as an amendment that is likely to affect to a significant degree any of the following:

  • the safety or physical or mental integrity of the subjects of the trial
  • the scientific value of the trial
  • the conduct or management of the trial, or the quality or safety of any investigational medicinal product used in the trial.

This would include:

  • A change of sponsor(s)
  • Appointment of a new Chief Investigator
  • Inclusion of a new research site in a study requiring a site specific assessment consideration of local issues in a multi-centre study
  • Appointment of a new Principal Investigator at a research site
  • Change of inclusion or exclusion criteria
  • Changes to the recruitment process
  • If the study is extended and it has the potential to generate significant cost implications

Researchers must not implement the substantial amendments until they receive MHRA/REC approval and R&D Approval unless this would compromise patient safety.

For further details refer to the following link:

Minor Amendments

  • Minor amendments cover changes such as:
  • Correction of typographical errors in the protocol or other study documentation
  • Appointment of new support staff
  • Changes in the documentation used for recording study data
  • Changes in the logistical arrangements for storing or transporting samples

Although R&D approval is not required for minor amendments the PI must notify the R&D Governance office of all amendments to a study.

For further details refer to the following link:

Who Decides Whether an Amendment is Substantial?

For a clinical trial of a medicinal product it is the sponsor of the trial who has the legal duty to decide. If the Trust is the sponsor then you should contact the R&D Governance Office. For all other research it is the Main REC which makes the decision. If you are in doubt whether to submit an amendment as minor or substantial you should seek advice from the R&D Governance Office or from the main REC.

Reporting Amendments

All amendments should be notified to the R&D Governance Office.  Please send a copy of the EU/NRES amendment form with a copy of any new versions of the protocol or supporting documentation to R&D Governance Office.

Failure to notify the R&D Governance Office of an amendment could result in the study being suspended, closed or under investigation under the Scientific Misconduct Procedures.

As well as reporting amendments to the R&D Governance Office, the CI or Sponsor may also be required to report it as follows:

  • Main Research Ethics Committee – all Substantial Amendments
  • MHRA – substantial amendment of a CTIMP
  • Participating Site PIs and R&D Offices – all amendments

Please note that full R&D approval will be issued once the relevant REC and MHRA approvals have been provided to the R&D Governance office. Substantial amendments will be authorised by the Head of R&D Governance.

Details on how to report substantial amendments can be found on the HRA website:

Urgent Safety Measures

In the interest of the subject Urgent Safety Measures may be implemented without delay. Any such amendments must be notified to REC, MHRA, Sponsor and R&D immediately and a Substantial Amendment submitted within three days, documenting the reasons for the measures taken.