Research Governance Monitoring How To

SLaM/IoPPN R&D: guidance for submission of amendments v3

This guidance is for researchers (including students) at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) or South London and Maudsley NHS Foundation Trust who require confirmation of sponsorship for an amendment to their researchstudy, where the original sponsorship was managed by the SLaM/IoPPN R&D office.Amendments are changes made to a research study after regulatory approval (e.g. a favourable ethical opinion, MHRA approval) has been given. Amendments can be ‘substantial’ or ‘non-substantial’ depending of the nature of the changes involved.

The Health Research Authority (HRA) oversees NHS ethics committees and a UK wide process for handling amendment for NHS R&D. This includes guidance on what constitutes substantial and non- substantial amendments, the amendment submission process as well as whether or not NHS sites need to be notified of an amendment.

If the R&D approvals for your study were originally managed through NIHR CSP, please be aware that as of 31 March 2016 amendments are categorised by the HRA and are no longer submitted to NIHR CSP.

Detailed guidance on amendments is on the HRA website:

Please also see the attached HRA leaflet ‘hraapproval-amendments’

Sponsorship

All amendments must be notified to the sponsor, and agreement from the study sponsor is required before an amendment is submitted to ethics and/or R&D. In order that we can review your amendment for sponsorship please email the following documents to us at . If your study is a Clinical Trial of an Investigational Medicinal Product, please ensure that you have also forwarded the amendment to your KHP CTO CRA for review.

If the amendment is substantial:- Draft IRAS substantial amendment form and new/amended documentation.
If the amendment is non-substantial:- HRA non-substantial amendment form (available from R&D office or new/amended documentation.

Please use the track change function to show where documents have been amended.

All amendments – please complete the amendment sponsor request form and return this to us with the amendment documents. The amendment sponsor request form asks for information on the following:

Whether the amendment is substantial or non substantial

Please refer to the guidance in appendix A when categorizing your amendment and contact us if you are unsure whether the amendment is substantial or non-substantial.

Whether the cost of the amendment is covered under your existing funding, or whether there is additional funding. For all new funding sources, please provide details and include a copy of the funding confirmation with the amendment, for example an external funding award letter, or email from the BRC or internal department. Where funds are held at SLaM or the IoPPN please also forward the SLaM or IoPPN grant cost code. We need this information to pass onto the relevant grants offices at IoPPN and SLaM and for our R&D reporting.
Whether the amendment affects the original end date of the study, and if so whether the funder has been notified and issued a funding extension (if required).

If you have any questions about your funding or how the amendment will impact on the funding conditions please contact your grant office directly for advice

Whether an annual progress report has been submitted to the REC within the last 12 months (as required by the NHS ethics service, and for our sponsor records). If not, please include a completed annual progress report with your amendment documents when you send them to us for review. Details are on the HRA website here:
If your amendment involves changes to PET scans (dosage or number of additional scans),the NHS REC will need reauthorization from the medical physics experts. When you send us the Notice of Substantial Amendment form, please make sure that the reauthorised NHS REC form is included with your submission for us to review and confirm sponsorship. You can request the signatures from the CI and the sponsor after we confirm sponsorship.

Please list the NHS trusts that have given R&D approval/confirmed capacity and capability. We need this to ensure they are all notified of the amendment and for our sponsor records. Please also list any NHS trusts (if any) where you have submitted an R&D application and approval is pending.

When we receive your amendment in the R&D office we will acknowledge receipt and it will be reviewed by a facilitator who will contact you if there are any changes required or if we need more information.

Sponsor sign off for amendments

When the amendment is ready for submission we will arrange sponsor sign off for you. Once this is in place and you have the sponsor and Chief Investigator signatures please do the following (instructions will also be included in the sponsorship confirmation email):

Submission of amendment

Email the amendment and documents in a zip file to the REC manager (contact details are on your ethics approval letter, contact details for all NHS RECs can also be found on the HRA website), and copy in the HRA

Substantial amendments will be validated and then reviewed by REC subcommittee, or occasionally a full committee. The outcome will be confirmed to you by formal letter within 35 days.
Non-substantial amendments or any amendments that do not require NHS REC review should be submitted by email to . using the HRA non-substantial amendment form. Where a non-substantial amendment is to be notified to the REC for information only (for example if the non-substantial amendment involves a change to the protocol or any documents originally reviewed by the REC), copy the REC into the email to the HRA.

If your study is a CTIMP, your KHP CTO CRA will liaise with you regarding the MHRA submission of the amendment, if this is needed.

Notifying sites of amendments and NHS R&D review

In terms of site approval and whether NHS sites are required to be notified of amendments, the Health Research Authority (HRA) groups amendments into three different categories (A, B and C) for the purpose of handling them in a manner appropriate to the amendment and who needs to review it The categorization of your amendment will be confirmed by the HRA when you submit the amendment for review. The classifications are as follows:

Category A: the amendment affects all sites that will all need to review.
Category B: the amendment affects specific sites, these sites will need to review
Category C: No sites need to review and you can implement the amendment as soon as you have REC approval (if this is required for the amendment).

Where sites are required to review the amendment they have 35 days (or until REC approves if this is after the 35 day date) to tell you they are not able to accommodate amendment or to or ask for more time for review. You can then implement the amendment.

Please see Appendix B for the HRA categorisations of amendments

When the HRA has categorised the amendment and sites need to be informed, please follow the steps on the flowchart in the HRA leaflet ‘hraapproval-amendments’

The R&D office will support you with notifying sites

Please check that you have the email contact details for the R&D offices of all sites involved. An up to date contacts list is on the R&D forum website:

Please copy all correspondence to our R&D office email address . As the sponsoring R&D office we are responsible for ensuring that your amendments go through the correct approvals process and are notified to sites appropriately, and that we keep a full record of the amendment.

Please be aware that it is the Chief Investigator’s responsibility to ensure that sites and local PIs have the correct up to date REC approved study documents. This is not provided by local R&D offices.
Appendix A

Categorising amendments to research projects (non CTIMPS)

HRAdefinition of a substantial amendment: one that is likely to affect to a significant degree:

(a) the safety or physical or mental integrity of the subjects of the trial,

(b) the scientific value of the trial,

(d) the quality or safety of any investigational medicinal product used in the trial.

HRAguidance on whether an amendment is substantial:

‘In deciding whether an amendment is substantial, consideration needs to be given to whether the proposed changes will affect the research “to a significant degree”. Particular account should be taken of any implications for the safety or welfare of participants, and of any information that participants might require to give informed consent to continue to participate in the research as amended. It is recommended that where there is any doubt about the potential implications of the amendment for participants, it should be treated as a substantial amendment and ethically reviewed by the REC’

The following changes should normally be regarded as substantial:

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;
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. -

Minor amendments: There will be changes to the details of research that have no significant implications for participants or for the conduct, management or scientific value of the study and can be regarded as non-substantial or minor amendments. Examples might be as follows:

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 (please note that we have been advised by the HRA that this only applies to key collaborators listed at A63)
changes to the research team at particular trial sites (other than appointment of a new principal investigator in a CTIMP); (please note that we have been advised by the HRA that this only applies to PIs)
changes in funding arrangements;
changes in the documentation used by the research team for recording study data; (please note that we have been advised by the HRA that this only applies where these changes mean that there is a change to the protocol)
changes in the logistical arrangements for storing or transporting samples;
inclusion of new sites and investigators in studies other than CTIMPs;
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 main REC for information.

Amendments requiring submission of a new application NRES SOPS v5.1

A new application should only be required where a proposed amendment would fundamentally alter the nature of the research and the extent of the involvement of, or risk to, existing and/or potential participants. Examples might be where the proposed amendment involves:

A change in the primary purpose or objective of the research, such as introduction of additional genetic studies;
A substantial change in research methodology;
Introduction of new classes of investigations or other interventions (rather than simply re-scheduling or modifying those already approved);
Recruitment of a new type of participant (especially if these would be regarded as being from vulnerable groups);
A proposed sub-study with a different Chief Investigator and/or an intention to publish the results separately from the parent study.

Where an amendment involves the submission of a separate protocol, the REC should normally require the submission of a new application.

Appendix B

HRA categorisation of amendments A,B and C

Category A – Amendment to a research study that ALL participating NHS organisations are expected to consider
This category includes any amendment to a research study that has implications for, or affects, ALL participating NHS organisations hosting the research study.
All participating NHS organisations will be informed of, and have access to the amendment.
All participating NHS organisations are expected to consider the amendment to determine whether they are able to continue NHS research permission.

Category B – Amendment to a research study that only those participating NHS organisations affected by the amendment are expected to consider
This category includes any amendment to a research study that has implications for, or affects, SPECIFIC participating NHS organisations hosting the research study.
Only those participating NHS organisations affected by the amendment will be informed of the amendment. However, all participating NHS organisations will have access to the amendment through the relevant national co ordinating function.
Only those participating NHS organisations affected by the amendment are expected to consider the amendment to determine whether they are able to continue NHS research permission. Note: Where the amendment is the addition of a new research site, the submission of a SSI application for a new research site should proceed through the NHS permission process appropriate to the addition of a new site in accordance with the requirements of the nation where the new research site is to be added.

Category C – Amendment to a research study that participating NHS organisations are not expected to consider
This category includes any amendment to a research study that has no implications that require management or oversight by the participating NHS organisations hosting the research study.
All participating NHS organisations will have access to the amendment.
Participating NHS organisations are NOT expected to consider the amendment or give continued permission for these amendments.