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Amendments

Amendment guidance - all review bodies



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 the National Offender Management Service
Notifying amendments to HRA Approval



Notifying amendments to the Research Ethics Committee

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.

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

Substantial amendments

A substantial amendment is defined as a change to the terms of the REC application, the protocol or any other document submitted with the application, 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
Addition of new research sites or changes to the local Principal Investigators listed in Part C of IRAS qualify as substantial amendments if the study requires site-specific assessment (SSA). Please refer to the correspondence from your Research Ethics Committee to check whether your study requires SSA, or seek advice from the REC office.

Notifying substantial amendments - CTIMPs

For all CTIMPs, substantial amendments must be notified to the main REC and the MHRA using the European Commission form, which is available in IRAS or available on the EudraCT website at http://eudract.emea.europa.eu/document.html.The form should be authorised by the named applicant.

Please submit a single copy of the relevant form to the REC, together with all relevant enclosures.

For guidance on submission of substantial amendments to the MHRA, please see http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Clinicaltrials/MakingclinicaltrialsubmissionstotheMHRA/index.htm.

All substantial amendments should be approved in principle by the sponsor(s) before submission.

Notifying substantial amendments - all other projects

Please use the Notice of Substantial Amendment form available in IRAS. Access to the form will be enabled in IRAS as soon as your Submission History for the REC form shows there is a completed version of your initial application for ethical review.

The completed Notice of Substantial Amendment form should be authorised using electronic authorisation in IRAS.

Please submit a single copy of the form to the REC, together with all relevant enclosures.

All substantial amendments should be approved in principle by the sponsor(s) before submission.

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

All amendments made during your study, both substantial and non-substantial, should be notified using the appropriate form.

For multi-centre studies, the form and amended documents should be submitted to the coordinating function for where the lead NHS/HSC office is located:

For single-centre studies, please contact the lead nation contact listed above where the single-centre study is in either England or Wales. If the single-centre study is in Scotland or Northern Ireland please submit the amendment directly to the site.

The amendment should be notified in parallel with any ethical and regulatory review(s) so that the implications of the amendment can be assessed and necessary arrangements made.

The Sponsor (or delegate) is responsible for providing details of the amendment, including copies of revised documents, to all participating investigators and study teams.

For further information on amendments including forms and categorisation of amendments please see the HRA website.

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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
Addition of new trial sites or changes to investigators listed in the initial applications to MHRA and the ethics committee qualify as substantial amendments.

Notifying substantial amendments Substantial amendments to CTIMPs must be notified using the European Commission form, available in IRAS and in 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.
Notifications should be sent directly to MHRA Devices. Details of where to send notifications can be found on the MHRA website at:
http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=194

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Notifying amendments to the Confidentiality Advisory Group (CAG)

CAG should be notified for information of all amendments to the information provided in your original application.

Please notify CAG in writing. It is not necessary to submit a Notice of Substantial Amendment form.

Amendments may be implemented immediately. CAG will contact you if any further information is required or if the amendment could affect the approval given under Section 251 of the NHS Act 2006.

Further guidance may be sought from the Confidentiality Advice Team (see Contact Us).

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Notifying amendments to ARSAC

ARSAC should be notified for information of any changes to the administration of radioactive materials exposure during a study, e.g. dose changes, new modalities, new classes of study participant.

Such changes will normally meet the criteria for notifying substantial amendments to the Research Ethics Committee (or GTAC). Please provide ARSAC with a copy of the Notice of Substantial Amendment when this is submitted to the REC, together with relevant enclosures (e.g. amendments to protocol and Participant Information Sheet).

In a multi-site study, it is not necessary for each ARSAC certificate holder to notify ARSAC. It is helpful if either the ARSAC certificate holder at the lead site or the trial co-ordinator can provide a single notification. ARSAC will contact certificate holders if any further information is required and/or the changes could affect existing certification.

Further guidance may be sought from the ARSAC Secretariat.

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Notifying amendments to the National Offender Management Service (NOMS)

The NOMS 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 Approval

Where a project has HRA Approval you are expected to notify both substantial and/or non-substantial amendments using the appropriate form. For more information please refer to HRA website.

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