- HRA Approval review of amendments
- NHS R&D review of amendments
- NHS Research Ethics Committee review of amendments
- MHRA (CTIMPs) review of amendments
- MHRA (Medical Devices) review of amendments
- Confidentiality Advisory Group (CAG)
- National Offender Management Service (NOMS)
Where a project has HRA Approval you are expected to notify both substantial and/or non-substantial amendments using the appropriate form.
For further information refer to the Preparing Amendments page.
- Substantial amendments:
Where HRA Approval included NHS REC review and:
- The REC is in England, you only need to submit the amendment to the REC.
- The REC is in Scotland, Wales or Northern Ireland you should submit the amendment to the REC and copy email@example.com.
Where the project did not require NHS REC review you should submit the substantial amendment to firstname.lastname@example.org.
- Other (non-substantial) amendments: Where the lead NHS R&D office is in England you should submit the amendment to email@example.com. Where the lead NHS/HSC R&D office is outside England, please follow the instructions below. Information will be shared with the HRA if there are NHS sites in England.
Where the amendment includes notification to the REC they will process the notification in accordance with REC standard procedures.
The HRA Assessment Team will categorise the amendment according to the UK amendments process and inform the applicant within 5 days. If there are participating NHS/HSC sites in other nations, the HRA will share the amendment and categorisation with the other participating nations.
The applicant can then send the amendment and the categorisation information to participating NHS organisations so that, where necessary, arrangements can be put in place to continue the site’s capacity and capability to deliver the study.
It is the applicant’s responsibility to communicate the categorisation and the amendment to English sites (i.e. the local research team, the R&D office and the LCRN, where appropriate).
- a flow chart outlining the amendment process is available in the Training Resources section of the HRA website
- a template email for sponsors to share information with sites can be downloaded here.
Amendments for studies set up using pre-HRA Approval processes are submitted in exactly the same way as HRA Approval studies. Where the amendment introduces a new site for a HRA Approval study special arrangements apply. Click here for further guidance.
For studies led in Scotland, Wales and Northern Ireland
For studies where the lead NHS R&D office is in Northern Ireland, Scotland or Wales the categorisation (see below) will be undertaken by the lead nation. Compatibility arrangements are in place across the 4 UK nations and amendments shared across participating UK nations.
All amendments made during your study, after NHS/HSC permission has been gained, should be notified to NHS/HSC R&D. This applies both to substantial and non-substantial amendments.
Amendments must be notified using the appropriate form. For further information refer to Preparing Amendments page.
For multi-centre studies, the form and amended documents should be submitted to the lead nation coordinating function as follows:
- Northern Ireland
Amendments should be emailed to firstname.lastname@example.org
Amendments should be emailed to nhsg.NRSPCC@nhs.net
Amendments should be emailed to email@example.com
For single-centre studies please contact the lead nation coordinating function for advice on submission.
The amendment should be notified in parallel with ethical and regulatory review so that the implications of the amendment can be assessed and necessary arrangements made.
Note that the Sponsor/CI is responsible for providing details of the amendment, including copies of revised documents, to all participating investigators and study teams.
Arrangements are being put in place across the UK for categorisation of amendments into those that need review by individual NHS organisations, and those that can be implemented once approved by the ethics committee (and MHRA or other regulatory body), where relevant. Please refer to the leaflet for researchers (v1.1, November 2014; pdf) and information about the principles of this UK process for management of amendments is available in Resources.
A change control procedure should be initiated at each site informed about an amendment to allow the impact of the amendment to be assessed and relevant arrangements put into place at the site. Once approved by the ethics committee (and MHRA or other regulatory body, where relevant) the amendment should be implemented at the NHS organisation.
Finalising revised financial schedules and sending a formal confirmation of the continued permission of the NHS organisation can follow after the implementation, within an agreed timetable, in order to avoid delays to implementation of the amendment.
Where a site is unable to accommodate the requirements of an approved amendment, the research would have to be terminated at that site.
If amendments are not submitted to R&D offices as soon as possible, this may delay implementation of the amendment as it may not be possible to make the necessary practical arrangements, e.g. scheduling additional X-rays, to accommodate the requirements of the amendment.
Note: For studies led in England, refer to the section on HRA Approvals above.
Flow diagrams setting out the process of ethical review of substantial amendments (CTIMPs and non-CTIMPs) are provided in Resources.
Any valid amendment submitted as a substantial amendment will be accepted for review. If the sponsor is satisfied that an amendment is not substantial, there is no requirement to notify the REC although non-substantial amendments may be notified for information only at the sponsor’s discretion. Sponsors and CIs may seek advice from the REC office on whether an amendment should be considered substantial.
Please note that Notice of Substantial Amendment forms submitted to REC must be electronically authorised in IRAS; this will be checked at validation. Notice of Substantial Amendment forms generated from Minimal Dataset studies (i.e. function used for projects that pre-date IRAS) are currently exempt from this requirement.
For general information about notification of substantial amendments to the MHRA, what to submit and associated fees please refer to the MHRA website.
The following guidance only applies to amendments to clinical investigations of medical devices subject to regulation by the Competent Authority (i.e. those that have a Notice of No Objection from MHRA).
You must notify MHRA Devices of all proposed changes to the investigation (not only those classified as substantial amendments for the purposes of ethical review) and await a letter of no objection from MHRA Devices before you implement them. This includes changes made at the request of the REC. Failure to notify proposed changes could result in the manufacturer being liable to prosecution.
For details of how to notify MHRA refer to the MHRA website.
A research certificate can be extended if the subject numbers in the original application have not been met or if some of the originally specified investigations for individual subjects will fall outside the duration of the certificate. Such a request should be submitted by letter, containing all relevant information, rather than by a new application form.
Where a material change to the original application is minor, an application for variation of a certificate can be made by letter. This should include a full justification for the variation. Major changes will require an application for a new certificate.
All certificates relate to the appointment and facilities quoted in the application, and the ARSAC should be informed promptly of any material change in these circumstances since the certificate may need to be varied.
An amendment to your application should be made using the CAG amendment template. Where necessary your completed amendment form should be accompanied by revised/additional documentation. Please see guidance from the Confidentiality Advice Team if you are unsure what to provide.
You will need to submit an amendment to CAG any changes are made to the following:
- Data flows
- Data items
- Data sources
- Purposes of application
- Data controller (please note that an amended application form and supporting documents setting out the new data controller arrangements will be required, you are advised to contact the Confidentiality Advice Team prior to submission)
- Data processor
- Duration amendment
If you are unsure whether an amendment needs to be submitted after reviewing the template please contact the Confidentiality Advice Team. The CAT may advise that you submit the amendment for information only at this stage.
Once you have submitted the completed amendment form the Confidentiality Advice Team will confirm if the amendment contains sufficient information, whether it is valid and the process and timelines for its review. You may be asked to provide further information prior to confirmation that your amendment is valid.
If the amendment can be reviewed outside a full CAG meeting an outcome should be provided within 30 days of receipt of a valid amendment, if the amendment is referred to a full CAG meeting an outcome can be expected within 60 days of receipt of a valid amendment. The Confidentiality Advice Team will inform you if your amendment is referred to a full CAG meeting as soon as possible. Please note that final approval for the amendment will not come into effect until a final approval letter is issued. The possible outcomes of review of the amendment are that the amendment is:
- Fully supported
- Conditionally supported
- Not supported
The National Research Coordinator should be notified of all amendments to the information provided in your original application. Amendments to the scope or nature of an approved research project must not be made without prior agreement.
You should be aware that it is not necessary to submit a Notice of Substantial Amendment form for this review body.