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Amendments

Amendment guidance - all review bodies



Coronavirus / COVID-19 - key guidance




IMPORTANT:

On 2 June 2020 changes were introduced to the way amendments are notified to Research Ethics Committees and NHS/HSC



Notifying Amendments to projects with NHS REC review and/or HRA and HCRW Approval / NHS/HSC R&D permissions

Notifying amendments to the Research Ethics Committee
Notifying amendments to NHS/HSC R&D offices
Notifying amendments to MHRA Medicines
Notifying amendments to MHRA Devices
Notifying amendments to the Confidentiality Advisory Group (CAG)
Notifying amendments to ARSAC
Notifying amendments to Her Majesty's Prison and Probation Service (HMPPS)
Notifying amendments to HRA Approval
Submission of amendments to Research Ethics Committees (RECs) and NHS/HSC on or after 2nd June 2020


IMPORTANT NOTE: If you are considering an amendment to comply with the General Data Protection Regulations (GDPR) then before you go any further please refer to the information on the Health Research Authority (HRA) website. In the majority of cases it will not be necessary to submit an amendment.

 

 



Notifying Amendments to project-based research with NHS REC review and/or HRA and HCRW Approval / NHS/HSC R&D permissions


On 2 June 2020 the process for preparing and submitting amendments to RECs and/or HRA and HCRW Approval / NHS/HSC R&D across the United Kingdom changed.
  • For all project-based research, notice of substantial amendment and non-substantial amendment forms are no longer used and have been replaced by the Amendment Tool.
  • Research Tissue Banks (RTBs) and Research Databases (RDBs) continue to use the Notice of Substantial Amendment Form generated in IRAS to notify substantial amendments to the REC.
  • For all types of research, amendments and supporting documentation should be uploaded and submitted for review via the online submission functionality.



Amendment Tool

 
The Amendment Tool applies to all project-based research (defined as any of the IRAS Project Filter question 2 categories except for RTBs and RDBs) and replaces the Notice of Substantial Amendment (NOSA) Form and the non-substantial amendment form.

For CTIMP amendments that require submission to the MHRA, the Tool must be completed alongside the Annex 2 form according to the instructions below.

It is no longer possible to create a new NOSA in IRAS for project-based research, and the non-substantial amendment template form is no longer used. Any amendments must be prepared using the Amendment Tool as amendment forms will no longer be accepted.

 

The process for completing the Amendment Tool is as follows:

1. Download the Amendment Tool from the link below and fill in information about your amendment on the ‘Amendment Tool’ tab, referring to the on-screen guidance notes. When complete, the declaration section should be completed by the sponsor or person with explicit delegated authority from the sponsor (authorised delegate). Amendments must not be submitted without prior authorisation from or on behalf of the sponsor. Please speak to your local Research and Development or Innovation Department and check local SOPs for the processes within your organisation.The ‘Lock for submission’ button will turn green when this is completed. If the amendment involves more than 10 changes, please contact amendments@hra.nhs.uk for support.

2. Click ‘Lock for submission’. This will generate a locked pdf copy of the completed tool. Save this to your computer ready for upload later.

3. If your project is a CTIMP and the amendment requires notification to MHRA (Medicines), in addition to the Amendment Tool you must also complete the European Commission “Annex 2” form for submission to MHRA. This is available under the ‘Annex 2’ tab of the Amendment Tool which is enabled only when the information entered into the amendment tool tab indicates that an Annex 2 notification is required. Refer to the on-screen guidance when completing this form. The Annex 2 form will need to be signed. This can be done by either adding in an image of the signature to the excel form prior to locking the form, or you can print, sign and scan the pdf. When complete, click ‘Lock for submission’ which will generate a locked pdf copy of the completed Annex 2 form. Save this to your computer ready for upload later. Alternatively it can be downloaded from the EudraCT website at http://ec.europa.eu/health/documents/eudralex/vol-10/index_en.htm.

 

The current version of the Amendment Tool is available here:

Amendment Tool v1.2 (11 Jun 2020).xlsm

 

NB: The Amendment Tool is an excel document which uses macros. A pop-up message may appear the first time you use the tool warning that macros have been disabled. In this case please select ‘Enable Content’.

 

Support

A brief training video introducing the amendment tool and its functionality can be accessed on youtube.

The Amendment Tool is not currently compliant with the Web Content Accessibility Guidelines version 2.1 AA standard for use with a screen reader. In the longer term we hope to move this over to a new digital platform and make it fully accessible. In the interim period, if you need help in accessing this tool, or if you have any technical issues with completing the tool, please email: amendments@hra.nhs.uk

For queries on how to complete the Amendment Tool or questions on the results from it, once complete, support can be accessed as follows. Please flag in the email subject that your query relates to the Amendment Tool so that it can be identified and handled efficiently.

For England and Wales led studies: amendments@hra.nhs.uk

For Scotland led studies: nhsg.nrspcc@nhs.net

For Northern Ireland led studies: Research.Amendments@hscni.net

The Amendment Tool is being rolled out as part of a new process for processing amendments across the UK. If you would like to provide feedback on the new process, please complete the online Amendment Process Survey

 

Online Submission of Amendments

 

As of 2 June 2020, all types of project submit amendments to the REC and/or HRA and HCRW Approval / NHS/HSC R&D coordinating functions via online amendment submission.

When you have completed the Amendment Tool (or Notice of Substantial Amendment form in the case of RTB and RDB projects) and finalised and gathered all supporting documentation for your amendment you should proceed to submit your amendment online.

The online amendment submission functionality requires a separate login to your main IRAS account. If you have not used it before you may need to set up a new account. Please follow the on-screen instructions. If you have any difficulty creating an account, please contact the Technical Helpdesk for support on: helpdesk@myresearchproject.org.uk

When you have logged in, refer to the on-screen step-by-step instructions which will guide you through the process. You will be asked to enter the IRAS ID, and answer some simple questions about your amendment. Some of these questions require you to enter information exactly as it appears on the Amendment Tool (or amendment form in the case of RTB/RDB projects), so have this available to refer to.

You can then upload all documentation relating to your amendment, and proceed to submit. You will receive an automated email to confirm submission of your amendment.

Upon submission the amendment will be shared with REC and/or NHS/HSC as applicable.

 

After you have submitted your amendment

For substantial amendments notified to the REC, you should await communication from the REC with the outcome of their review.

If your project involves the NHS/HSC, further details of the steps to take after you have submitted your amendment can be found here.

 

Modified Amendments

Where the REC gives an unfavourable opinion of a substantial amendment, the sponsor or Chief Investigator may submit a modified amendment taking into account the Committee’s concerns. In this case a new amendment tool should be completed, indicating that it relates to a modified amendment at the relevant question. It should then be submitted to the REC alongside all supporting documentation by email. Where applicable, the REC will share the amendment and Amendment Tool with the relevant national coordinating function for the lead nation.

Modified amendments must not be submitted using online submission.

REC email addresses can be looked up on the HRA website

 


Amendments to add the involvement of adults lacking capacity for the first time, or extend involvement of adults lacking capacity to a new nation

Because of the specific REC review requirements, it is not possible for this type of amendment to use online submission.

The type of amendment and level of information you need to provide will vary depending on the location of the lead nation and nation/s where the amendment will be implemented. You should therefore contact the REC that originally issued favourable opinion for the study, flagging in your covering email that the amendment involves adding the involvement of adults lacking capacity. They will be able to advise on how to submit and any additional steps you need to take. REC email addresses can be looked up on the HRA website.

 

Support

A brief training video introducing the online amendment submission functionality can be accessed on youtube.

For any technical queries about accessing or using online amendment submission, contact: helpdesk@myresearchproject.org.uk

 Any queries about the amendment itself should be directed to the REC that issued favourable opinion for the study.

Any queries about the amendment itself for non-REC studies can access support as follows. Please flag in the email subject that your query relates to an amendment and include the project IRAS ID so that it can be identified and handled efficiently.

For England and Wales led studies: amendments@hra.nhs.uk

For Scotland led studies: nhsg.nrspcc@nhs.net

For Northern Ireland led studies: Research.Amendments@hscni.net

 

 


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Notifying amendments to the Research Ethics Committee



IMPORTANT:

On 2 June 2020 changes were introduced to the way amendments are notified to Research Ethics Committees and NHS/HSC



Further ethical review is required for any substantial amendment made once the study has started. A favourable opinion must be obtained prior to implementing the amendment, unless it is an urgent safety measure.

For CTIMPs and clinical investigations of medical devices only, substantial amendments should also be notified prior to the start of the study where, exceptionally, significant changes are requested by the Medicines and Healthcare products Regulatory Agency (MHRA) as part of the regulatory approval process and these changes are relevant to ethical review.

For guidance on submission of substantial amendments to the MHRA, please see https://www.gov.uk/guidance/clinical-trials-for-medicines-manage-your-authorisation-report-safety-issues.

Guidance on notifying amendments to project-based research can be found here.

Notifying substantial amendments – Research Tissue Banks (RTBs) and Research Databases (RDBs)

 
Please use the Notice of Substantial Amendment form available in IRAS. This is created from the Amendment tab associated with the RTB/RDB form.


The completed Notice of Substantial Amendment form should be electronically authorised by all parties listed on the form’s authorisations tab in IRAS.


When authorisations are in place, submit of the final PDF of the form (created via the Submission Tab of amendment form) to the REC, together with all relevant enclosures via online amendment submission according to the instructions provided on the amendment form’s submission tab.


Further guidance

For further guidance about notifying substantial amendments to RECs and review procedures, please see the Health Research Authority (HRA) website

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Notifying amendments to NHS/HSC R&D offices



IMPORTANT:

On 2 June 2020 changes were introduced to the way amendments are notified to Research Ethics Committees and NHS/HSC





For guidance on managing amendments to research conducted in the NHS/HSC please refer to the guidance here.

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Notifying amendments to MHRA Medicines

Any substantial amendment to a clinical trial of an investigational medicinal product (CTIMP) must be notified both to the MHRA and the ethics committee before it is implemented, unless it is an urgent safety measure.

Notification is not required for amendments not meeting the criteria for substantial amendments.

Substantial amendments

A substantial amendment is a change to the terms of the request for clinical trial authorisation or the ethics committee application, or to the accompanying particulars or documents, which significantly affects one of the following:
  • The safety or physical or mental integrity of study participants
  • The conduct or management of the study
  • The scientific value of the study
  • The quality or safety of any investigational medicinal product used in the study

Notifying substantial amendments Substantial amendments to CTIMPs must be notified using the European Commission form, available under the 'Annex 2' tab of the Amendment Tool, or on the EudraCT website at: http://ec.europa.eu/health/documents/eudralex/vol-10/index_en.htm .

For further guidance about procedures for notifying substantial amendments to the MHRA, please see: https://www.gov.uk/guidance/clinical-trials-for-medicines-manage-your-authorisation-report-safety-issues



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Notifying amendments to MHRA Devices

The following guidance applies to amendments to clinical investigations of medical devices subject to regulation by the Competent Authority.

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.

When notifying MHRA of changes, please provide the following information in writing:
  • the MHRA reference number for the trial;
  • details of the proposed change(s) to the clinical investigation plan or the design of the device;
  • the reason for the change(s); and
  • a signed statement by or on behalf of the manufacturer that the proposed change(s) do not predictably increase the risk to the patient, user or third party.
  • A copy of the completed Amendment Tool
Notifications should be sent directly to MHRA Devices. Details of where to send notifications can be found on the MHRA website at: https://www.gov.uk/guidance/notify-mhra-about-a-clinical-investigation-for-a-medical-device 


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Submitting amendments to the Confidentiality Advisory Group (CAG)

CAG should be notified of all amendments to the information provided in your original application. This is because support to process confidential patient information without consent is based on the precise details originally provided to CAG and so any change will not be covered by the existing support until a formal amendment is made and the amendment is supported.

You will need to complete and submit an amendment form to CAG where changes are intended to any of the following:
  • Data flows
  • Data items
  • Data sources
  • Purpose 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 and/or you need further guidance please contact the Confidentiality Advice Team (CAT; see Contact Us). 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 the review of the amendment are that the amendment is:
  • Fully supported
  • Conditionally supported
  • Not supported


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Notifying amendments to ARSAC

ARSAC should be notified of any changes concerning the administration of radioactive substances as this may affect the approval granted. Such changes include, but are not limited to:
  • Changes to the study title
  • Changes to the number of administrations of radioactive substances from Section A1 of the original Preliminary Research Assessment (PRA) form
  • Addition or removal of a procedure involving the administration of a radioactive substance
  • Addition of a new study population with a different clinical condition (including changing the age of the participants)
  • Changes to the radiation risk information in the participant information sheet (PIS) following changes to the protocol


Such changes will normally meet the criteria for notifying substantial amendments to the Research Ethics Committee (or GTAC). Notification should be made to the ARSAC Support Unit by the sponsor, by email with the following information:
  1. Short summary of the changes
  2. Notice of Substantial Amendment when this is submitted to the REC
  3. Updated PRA form if there are changes to the number of administrations or procedures involving radioactive substances (note you will need to revise the integrated dataset Part A and/or Part B3 and then create an up to date PDF of the PRA form via the Submission tab)
  4. Any other relevant enclosures, for example Participant Information Sheet

All information should be emailed to the ARSAC Support Unit at ARSAC@phe.gov.uk .

Once you have submitted your amendment request, ARSAC will send you a reference number and details on how and when to pay the £250 fee.

While ARSAC assesses the amendment, you remain authorised within the limits of the initial submission and administrations may continue in line with the original application.

Once approval has been granted to you, individual installations can proceed with the amended study for all procedures on their licence. It is not necessary for each installation to notify ARSAC of amendments.

Further guidance may be found on the ARSAC website or by contacting the ARSAC Support Unit.

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Notifying amendments to Her Majesty's Prison and Probation Service (HMPPS)

The National Research Coordinator (details provided on Contact Us page) should be notified of all amendments to the information provided in your original application.

It is not necessary to submit a Notice of Substantial Amendment form.

Amendments to the scope or nature of an approved research project must not be made without prior agreement.

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Notifying amendments to HRA and HCRW Approval



IMPORTANT:

On 2 June 2020 changes were introduced to the way amendments are notified to Research Ethics Committees and NHS/HSC



Where a project has HRA and HCRW Approval you are expected to notify amendments according to the guidance here.

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Page last updated: 25 June 2020



 
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