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Amendments

Amendments are defined as changes to the protocol and other approved information.

This section covers:

  • Definitions of amendments:
    • Substantial
    • Non-substantial amendments
  • Preparing amendments for OUH sponsored studies
  • OUH R&D review of amendments
  • Documents required for valid local submission of amendments

Amendments are changes made to the research after review body approval has been given. The following sections provide information about each review body's requirements and, where appropriate, guidance about how different types of amendments are handled by that review body.

Amendments requiring approval cannot be implemented until the relevant approvals are in place, except in the case of urgent safety measures.

Where OUH is the research Sponsor, the R&D team review and approve all amendments to protocols before submission to regulatory bodies. This is essential to ensure that indemnity is not affected by the change(s).

Definition of amendments

Substantial amendments

A substantial amendment is defined as change to the terms of the protocol or any other supporting documentation that is likely to affect to a significant degree:

  • the safety or physical or mental integrity of participants
  • the scientific value of the research
  • the conduct or management of the research
  • the quality or safety of any investigational medicinal product used.

Addition of new sites, or appointment of a new Principal Investigator at an existing trial site (for CTIMPs only), are substantial amendments since they change the conduct or management of the research.

Examples of substantial amendments

  • 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;
  • Inclusion of a new trial site (not listed in the original application) in a CTIMP;
  • Appointment of a new Principal Investigator at a trial 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 REC application.

A substantial amendment is made after original approvals from the REC, MHRA (Clinical Trials only), Health Research Authority / NHS permission and Local Trust Management Approval have been received.

If the amendment requires immediate implementation due to safety concerns (Urgent Safety Measures) this must be discussed with the MHRA as soon as possible and a formal amendment submitted within three days.

In all other cases the REC, MHRA (Trials only), Sponsor Health Research Authority / NHS permission must approve substantial amendments, before they are implemented.

Amendment process post 31 March 2016

From 31 March 2016, all historic studies led from England, or with NHS sites in England, will go through an HRA amendment process - including all studies set up prior to CSP, through CSP, non CSP (ie, non-Portfolio) and HRA Approval studies).

Studies that did not originally have an HRA Approval will not have a full review undertaken when an amendment is submitted to the HRA and will not receive an HRA Approval - the HRA will simply review the amendment to ensure its legality.

However, if the amendment is to add a new site, it will be reviewed to come under HRA Approval so that the new sites confirm capacity and capability and are assured that it meets the national criteria. This will be a proportionate and pragmatic review and the HRA will request that it receives the current document set, but not a new submission.

There will be no requirement to complete a new IRAS form but there will be requirement to complete the Statement and Schedule.

HRA will see all amendments, including minor, and where ethical review is required, sponsor will receive REC favourable opinion for the amendment and 'continuing approval' for the amendment from HRA.

Local sites must review amendments insofar as that there will be a capacity and capability assessment of the impact of the amendment, in terms of continuing to deliver the study for which OUH will be Local Trust Management Approval.

Non-substantial amendments

Non-substantial amendments should be notified to the Sponsor where they may affect indemnity. However, they do not need REC, HRA or MHRA approval. Records of the amendment and when it was implemented must be kept in the Research File (Trial Master File for Clinical Trials).

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 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 (please see the changes outlined above for addition of new sites to studies that have not had an HRA approval, post 31 March 2016);

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 HRA and the main REC for information.

Preparing amendments for OUH sponsored studies

All amendments to OUH-sponsored research must be submitted to the R&D team for approval before submission to appropriate bodies for their approval, including non-substantial amendments.

Notice of substantial amendment forms are created in IRAS; the system automatically generates the type of notice of substantial amendment form that is appropriate to the project category.

To generate the Notice of Substantial Amendment form in IRAS, open your study, highlight the REC application on the Navigate page and then select the Amendment tab and follow the instructions provided. Notice of Substantial Amendment forms and any accompanying documentation should be emailed to the HRA / REC.

If you submitted your original NHS REC application using systems or procedures that pre-date IRAS, please create a minimal dataset in IRAS in order to create an amendment form.

You should summarise the change(s) included in the amendment and briefly explain the reasons in each case on the notice of amendment.

You should submit the documents that have been modified, showing both the previous and new wording so that the changes can be readily identified, with the form. Where the modified documents (for example, the study protocol) are lengthy and the changes are not so widespread or significant as to justify a new version, you can provide extracts or list the changes in a separate document.

The Sponsor or Chief Investigator may also include other supporting information, such as a summary of trial data, an updated safety analysis or a report from a trial monitoring committee. Where the amendment could significantly affect the scientific value of the research, you should provide further evidence of scientific and/or statistical review.

For CTIMPs, the EU Notification of Substantial Amendment form is used. This form is available in IRAS or may be obtained via EudraCT. In accordance with the European Commission guidance, the form may be submitted by the Sponsor, the Sponsor's legal representative, the Chief Investigator, or another person or organisation authorised by the Sponsor.

For non-CTIMPs, the NRES Notice of Substantial Amendment form generated in IRAS must be used. The form should be electronically authorised in IRAS by the Sponsor and the Chief Investigator. Without any of the authorisations, the amendment will not be validated.

Note: Notice of Substantial Amendment forms generated in Minimal Dataset projects (i.e. projects where original applications were made pre-IRAS) are exempt from requirement for electronic authorisations.

Once HRA / REC and/or MHRA approval has been received, the host sites for the research should be notified directly to the OUH R&D office. This applies both to substantial and non-substantial amendments.

OUH R&D review of amendments

For research where OUH is not the Sponsor but the host of the research, all amendments made during your study, by the Sponsor and Chief Investigator, should be notified to either the coordinated permission system that initially processed your application (CSP), or, where that system was not used, directly to the OUH R&D office. This applies both to substantial and non-substantial amendments.

All amendments can be submitted directly to the R&D office via email.

For research where OUH is not the sponsor but the host of the research, a valid set of documents will be required before the amendment is approved. OUH approval may be through the issue of an email or letter approval depending on the nature of the amendment. Some amendments may generate a change to the contract for the research.

Documents required for valid local submission of amendments

Substantial amendments

CTIMP

  • Valid EU Notification of Substantial Amendment form
  • All supporting documents submitted to REC
  • Local documents with local headers and contact details
  • REC approval letter
  • MHRA approval letter (please highlight if MHRA approval is not required)
  • Detailed description of the amendment

Non-substantial amendments

CTIMP

  • REC Acknowledgement (if applicable)
  • Supporting documents
  • Local documents with local headers and contact details
  • Description of the amendment

Substantial Amendments

Non-CTIMP

  • Valid NRES Notice of Substantial Amendment form
  • All supporting documents submitted to REC
  • Local documents with local headers and contact details
  • REC approval letter
  • Detailed description of the amendment

Non-Substantial Amendments

Non-CTIMP

  • REC Acknowledgement (if applicable)
  • Supporting documents
  • Local documents with local headers and contact details
  • Description of the amendment