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Amendments for projects conducted in NHS/HSC



Amendments for projects conducted in the NHS/HSC



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 provided on behalf of the UK which can be found on the Health Research Authority (HRA) website. In the majority of cases it will not be necessary to submit an amendment.

Introduction


An amendment is a change to a research project after an applicant has received the initial approvals. If you plan to make an amendment to your research project, you will need to determine whether you need to notify the review body(ies) from whom you have received approvals. Different review bodies have different requirements. These are set out in IRAS guidance on notification of amendments.

IMPORTANT: The guidance provided on this page applies only to research projects with NHS/HSC R&D Permission or HRA and HCRW Approval. If your study does not yet have these, please refer to IRAS Help pages for seeking NHS/HSC R&D Permission or HRA and HCRW Approval.

The guidance on this page does not apply to:
  • Research Tissue Banks (RTB) and Research Databases (RDB) as these do not need NHS/HSC R&D Permission or HRA and HCRW Approval;
  • Urgent Safety Measures. These should be sent to all participating organisations on receipt to ensure the participants' safety. Subsequent notifications, including resulting amendments should be submitted, as appropriate and according to relevant guidance; or
  • Notifications of the end of a study. These are not amendments and should be notified using the appropriate Notice of End of Study form.


The guidance is divided into the following sections:

Amendment classifications


All amendments to projects with HRA and HCRW Approval or NHS/HSC R&D permissions should be submitted according to the process that is applicable for your project except where the activity should not be notified as an amendment.

Once you have submitted the amendment, it is categorised by the lead country to ensure that the amendment is handled in a manner that is appropriate to the scale of the amendment and the potential risks to, and the liability of, the NHS/HSC organisation(s) implementing the amendment - see table below. Please note that:
  1. This categorisation is completed once for each amendment submission; and
  2. When you receive the correspondence confirming the category it will contain instructions about how to proceed and so please ensure that you read this correspondence in full.


Category: This category includes any amendment to a research project that has:

A
Implications for, or affects, all participating NHS/HSC organisations hosting the research project.

B
Implications for, or affects, specific participating NHS/HSC organisations hosting the research project.

C
No implications that require management or oversight by the participating NHS/HSC organisations hosting the research project. However the amendment should still be provided for information.

Note - Updated Investigator Brochure (IB; Clinical Trials of Investigational Medicinal Products (CTIMPs) only):
Where the IB update, annual or otherwise, constitutes a non-substantial amendment for REC and MHRA and this is the only amendment (e.g. the update to IB does not give rise to updated pharmacy manual or protocol) the updated IB should not be submitted for categorisation. These amendments will always be category C and they will not be assessed by NHS/HSC if submitted. The IB should be provided to each participating NHS/HSC organisation.

New NHS/HSC site
Guidance on adding additional NHS/HSC sites is provided in the section below.
Where the amendment is to add a new NHS/HSC site to the project, the set-up of this new site should proceed according to the process for local study set-up for the nation where the new site is located.


For single centre studies in Northern Ireland and Scotland, the above categorisation processes do not apply as there is no study wide review for single centre studies in these nations; the amendment can be submitted directly to the site. Please refer to the table below for details of how and where to submit your amendment in this situation.

Applicants may be familiar with amendments being classified as 'substantial' or 'non-substantial' (also known as 'minor'). These distinctions are used by both Research Ethics Committees (RECs) within the UK Health Departments' Research Ethics Service (for all research) and the Medicines and Healthcare products Regulatory Agency (MHRA) for Clinical Trials of Investigational Medicinal Products (CTIMPs). It is the Sponsors responsibility to decide whether an amendment is substantial and therefore whether it needs to be notified to REC and/or MHRA. While this system of classifying amendments is not used by NHS/HSC (see table above), if an amendment is substantial the same form may be used to notify REC/MHRA and NHS/HSC. For more information see sections below on 'Amendment notification forms' and 'How to submit amendments'.

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Amendments to add additional NHS/HSC sites


General considerations

The addition of new NHS/HSC participating organisations should be submitted separately to other amendments in order to expedite the review process.

If you are adding a site that is in a nation not previously involved in the project, you should make this clear when submitting your amendment to the lead nation. This will help to ensure that the relevant information is passed on as efficiently as possible.

If your amendment involves the addition of non-NHS sites only, you do not need to notify this as an amendment to NHS/HSC as long as there are no direct implications for any participating NHS/HSC sites.

You do not need to provide an updated IRAS Form Part C alongside an amendment to add a new NHS/HSC site. You should provide the new site name on the amendment form.

Northern Ireland or Scotland

For new NHS/HSC sites in Northern Ireland or Scotland an NHS/HSC Site Specific Information (SSI) Form should be emailed to the participating organisation along with any relevant supporting documentation as listed on the NHS/HSC SSI Form’s checklist tab.

England or Wales

NHS sites in England or Wales do not use NHS/HSC SSI Forms. Please refer to the section on “Expectations for site level information for participating NHS organisations in England and Wales under HRA and HCRW Approval.”

For non-commercial projects, a Statement of Activities (SoA), and a Schedule of Events (SoE) should be provided for each NHS ‘site type’. If the new site(s) being added are:
  • a ‘site type’ covered by an existing, approved SoA/SoE, then you should confirm in your amendment form that the new site(s) are covered as an existing site type.
  • new site types, then a new generic SoA/SoE for this 'site type' should be completed and submitted alongside the amendment.



Amendments to add Participant Identification Centres (PICs)

PICs are organisations through which potential participants will be identified and referred to research sites, but at which no research activity will take place. More information on PICs can be found within the IRAS Help section.

If you wish to add PICs to your project and the use of PICs was not described in your original application or a subsequent amendment (i.e. the response to IRAS Form question A73-1 was ‘No’) then you will first need to submit a substantial amendment to add this method of recruitment to your project.

If the use of PICs was described in your original application or a subsequent amendment and you now wish to add additional PICs, you will notify this differently as follows, depending on the location of the PIC:
  • England: If you are adding PICs in England, you do not need to submit this to the lead nation for categorisation. You do need to notify the R&D office of the PIC and work with them and the local research team to ensure that they have everything in place to undertake PIC activity.
  • Northern Ireland, Scotland or Wales: If you are adding PICs in Northern Ireland, Scotland or Wales, the relevant National Coordinating Function will facilitate the setting up of a PIC in their region. In order to initiate this you should submit the addition of the PIC as a non-substantial amendment to the lead nation for the study. They will share this information with the National Coordinating Function of the participating nation(s), who will communicate with the R&D office of the PIC on your behalf. You should liaise directly with the research team at the PIC to ensure that they have all the necessary documentation and resources in place to undertake PIC activity. No activity should take place at the PIC until local permission (i.e. R&D permission for sites in Northern Ireland or Scotland, or confirmation of capacity and capability for sites in Wales) has been granted.


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Activities that should not be notified to NHS/HSC as amendments


There are some activities that are undertaken during a project, which should not be submitted as amendments for NHS/HSC review and categorisation. These include:
  1. Addition of translated versions of participant facing documentation.
  2. Where there has been a routine review or renewal process during the study with an outcome that does not change the research project. For example:
    • Where a Data Monitoring Committee meeting concludes a study should proceed without any changes.
    • Where insurance is renewed but there is no change to the level or breadth of cover.
    • Annual updates and reviews of study documentation that do not make any changes, such as an annually updated edition of the Investigator's Brochure where no changes are made except the last review date.
  3. Changes to the research team at participating NHS/HSC organisations, except where it is the appointment of a new Principal Investigator (PI). Appointment of a new PI at a participating NHS/HSC organisation is notifiable as an amendment.
  4. Updating of participant information wording to comply with GDPR requirements where only the unmodified standard wording provided by HRA, on behalf of the UK, has been used.
  5. Addition of new Participant Identification Centres (PICs) in England.

Note: while the activities listed above should not be submitted as amendments for review and categorisation, they may need to be sent to participating sites (Principal Investigator (PI), site teams, local NHS/HSC R&D offices) so that the local site files can be updated. In these circumstances, the local NHS/HSC R&D office are not expected to review and categorise the amendment.

There may also be amendments of a confidential nature that the Sponsor is required to submit to the MHRA that have no implications for, or affect, the participating NHS/HSC organisations hosting the research project. In these circumstances the amendments should not be notified to NHS/HSC. This would also apply to updates to an Investigator's Brochure (IB) that do not have any impact on participating NHS/HSC organisations, the departments within participating NHS/HSC organisations supporting the research and/or the researchers at the site(s).

If, after reading the guidance above, you are not sure whether the change to your project should be submitted for NHS/HSC review and categorisation, please send an email to IRAS.queries@nhs.net providing as much information as possible about your proposed amendment and your IRAS ID. Advice will be sought from a group that has been established for reaching UK-wide consensus on amendments that do not need NHS/HSC review and categorisation. We aim to provide this advice within 5 working days of your request.

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Grouping of amendments


Unless your amendment is time critical, you can group several changes together in one submission. If the change is time critical you should submit this change on its own. The grouping of changes facilitates the review of your amendment and facilitates the implementation of the changes to your project.

Some examples of when grouping may be appropriate are:
  • When you need to make a series of amendments all relating to a specific change.
    For example, an amendment to update the protocol, which will lead to revision of the participant information sheet (PIS) and consent form. These changed documents should be submitted as one package of related amendments.
  • A series of sequential amendments with unrelated changes all within a short space of time of each other (often at the start of a study). In this situation you are encouraged to consider submitting all amendments together.
  • Where you expect the likely categorisation of several amendments that you wish to submit within a short timeframe to be the same, then you should consider whether them to submit them as a single package. Note that where a package of amendments is submitted the whole package is given the highest category of any of the component amendments (e.g. if your package includes amendments that are individually category A and C, the whole group would be categorised as A).
  • Where you wish to correct simple typographical errors, which do not change the meaning of the protocol, or which alter the format, but not the wording, of the project documentation. These changes may be included when you submit a future amendment.

The following amendments should not be grouped with other amendments:
  • Addition of new NHS/HSC participating organisations; and/or
  • Change of local Principal Investigator (PI).

The addition of new NHS/HSC participating organisations and/or changes to PIs should be submitted separately to other amendments to expedite the review process. While it is best practice to have had an initial discussion with a site, it is not necessary to have agreed with the hosting organisation that they will be a site before submitting the amendment to add the new NHS/HSC site. Note that if you are adding multiple new NHS/HSC sites then these may be grouped into a single amendment submission.

IMPORTANT NOTE: If you are intending to group your amendments and the package includes both substantial and non-substantial then you should use a substantial amendment form to describe the substantial amendment(s) and a non-substantial amendment form to describe the non-substantial amendment(s). You should submit the forms and supporting documentation according to the process that is relevant for your project; in some instances this may mean you should not group the substantial and non-substantial amendments.

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Amendment notification forms


Substantial amendments

Should be notified using a Notice of Substantial Amendment Form. These forms are generated in IRAS by navigating to the Amendments tab of your project form, and clicking 'Create Notice of Substantial Amendment' button. The response you have given to IRAS Filter Question 2 will ensure that IRAS generates the appropriate type of substantial amendment form for your study. The same Notice of Substantial Amendment form should be used to notify the amendment to all the appropriate bodies i.e. REC, MHRA (CTIMPs) and NHS/HSC. The form should be appropriately authorised prior to submission and any supporting documentation supplied as part of your notification package. Note: if the project is a CTIMP then you may use the 'Annex 2 Form' available from EudraCT as an alternative to using the form generated in IRAS although the forms are identical.


Non-substantial amendments and projects that do not have NHS/HSC REC review

Amendments should be notified using the template form for notifying non-substantial amendments.

The Non-Substantial Amendment Form should be authorised prior to submission.

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Numbering your amendments


To keep track of your amendments, you should allocate each amendment a reference number. We recommend that the amendments are numbered sequentially. You should also maintain a clear record of the amendments in the form of an amendment log. An example of an amendment log is provided here. If you are notifying several review bodies of an amendment, consistency of approach in the numbering system is recommended to avoid confusion.

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Submitting your amendment for NHS/HSC review and categorisation


It is not currently possible to submit amendments electronically in IRAS. You should therefore email your amendment (form(s) and any supporting documentation). The route for submission of your amendment to NHS/HSC will depend on a number of factors. Please refer to the table below:

Lead country: Location of REC: Is the amendment a Notification of Substantial Amendment that is submitted to REC?* Submit your amendment to NHS/HSC as follows:
England England Yes Email to the REC only (they will share with the HRA Amendments team)
Scotland, Wales or Northern Ireland Yes Email to hra.amendments@nhs.net at the same time as submitting to the REC
Anywhere in the UK No Email to: hra.amendments@nhs.net only

Northern Ireland - multi centre studies Anywhere in the UK Yes or No Email to: research.amendments@hscni.net
Northern Ireland - single centre studies Yes or No Submit directly to HSC Trust / research site

Scotland - multi centre studies Anywhere in the UK Yes or No Email to: nhsg.NRSPCC@nhs.net
Scotland - single centre studies Yes or No Email directly to the NHS Board

Wales Anywhere in the UK Yes or No Email to: Research-permissions@wales.nhs.uk


* More information on the requirements for notifying the REC of an amendment can be found here.

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What happens after you have submitted your amendment?



After you have submitted your amendment you should wait to receive communication, which will usually be in the form of an email or letter. IMPORTANT: You should read all correspondence very carefully as it may require further action from you before the amendment can be implemented.

The communication will confirm:
  • Whether the submission is complete.
  • The amendment category A, B or C or new NHS/HSC site.
  • The implementation date (if applicable).
  • How to implement the amendment:
    • For category A and B amendments you should follow the guidance below on how to implement, and what steps you should take with your participating NHS/HSC organisations. Note that the categorisation communication you receive will link to the guidance below.
    • For category C and new NHS/HSC site only amendments the communication will provide information on how to implement the amendment.

Please note the following points which apply to NHS/HSC organisations in all nations:
  • Sponsors should not expect to receive a letter or email of confirmation from NHS/HSC organisations before implementing the amendment.
  • Category A and B amendments may be implemented sooner than 35 days in cases where all regulatory approvals have been issued and where the NHS/HSC organisation has confirmed that the amendment may be implemented prior to this date.
  • The coordinating function of the lead nation will, upon categorisation, share the amendment with the coordinating function of any other participating nation(s). There is no need to separately submit to each nation.


Implementing category A and B amendments in participating NHS/HSC organisations


In England and/or Wales:

Once you receive your categorisation email, you should share your notice of amendment and, if applicable, amended documents together with the categorisation email with relevant participating NHS organisations in England and/or Wales.
  • In doing so, you should include the NHS R&D Office, LCRN (where applicable) as well as the local research team.
  • A template email to notify participating NHS organisations in England and/or Wales is provided on the HRA website.

Once you have notified participating NHS organisations in England and/or Wales of the amendment, they should prepare to implement the amendment.
You may then implement your amendment at all participating NHS organisations in England and/or Wales 35 calendar days from the day on which you provide the organisation(s) with the categorisation email and your amended documents; so long as:
  • HRA and HCRW Approval has been issued for the amendment. You should first check your categorisation email as to whether HRA and HCRW Approval for the amendment is listed as pending or as issued.
    • Where it is pending, you should not implement the amendment until you receive a separate email from the HRA or HCRW confirming HRA and HCRW Approval
    • Where it is approved, you may implement the amendment after 35 days, providing points (b) and (c) are satisfied.
    • If HRA and HCRW Approval is issued after the 35 day deadline, you may implement the amendment upon receipt of HRA and HCRW Approval, providing points (b) and (c) are satisfied.

  • A participating NHS organisation does not request additional time to assess.
    • If you are notified that a participating organisation needs more time to assess the amendment you should not implement until they are ready to do so. You should work with the organisation to resolve any outstanding issues.

  • A participating NHS organisation does not decline to implement the amendment
    • If a participating NHS organisation declines the amendment, you should discuss with that organisation and take appropriate actions in agreement with the NHS organisation.


In Northern Ireland and/or Scotland

For multicentre studies with sites in Northern Ireland or Scotland, the National Coordinating Function will provide the categorisation email. There is no need for you to send the categorisation email to the R&D offices of participating organisations in these nations as the National Coordinating Function will pass this on to them along with any amended documents on your behalf.

However, you should share these documents upon receipt of the categorisation email with the research teams at relevant participating NHS/HSC organisations in Northern Ireland and/or Scotland who should prepare to implement the amendment.

You may then implement your amendment at all participating NHS/HSC organisations in Northern Ireland and/or Scotland on the date that is provided in your categorisation email, so long as:
  • You have received all regulatory approvals necessary for the amendment
    • If the last regulatory approval is received after the 35 day deadline, you may implement the amendment upon receipt of this approval, providing points (b) and (c) are satisfied.
  • A participating NHS/HSC organisation does not request additional time to assess.
    • If you are notified that a participating organisation needs more time to assess the amendment you should not implement until they are ready to do so. You should work with the organisation to resolve any outstanding issues.
  • A participating NHS/HSC organisation does not decline to implement the amendment
    • If a participating NHS/HSC organisation declines the amendment, you should discuss with that organisation and take appropriate actions in agreement with the NHS/HSC organisation.




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Guidance version 2.0; published 15 November 2018



 
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