Change your protocol, update your authorisation, report safety issues, submit safety updates and complete your end-of-trial study report.

Apply to change your trial’s protocol or documentation

These changes count as a substantial amendment to your clinical trial authorisation. You need to send a notification of amendment form, a revised application form and other documents to the Medicines and Healthcare Products Regulatory Agency (MHRA):

  • covering letter outlining the substantial and any non-substantial changes
  • signed notification of amendment form from the European Commission website
  • updated XML and PDF versions of the clinical trial application form if it’s changed since the last submission
  • proof of payment of your fee
  • reasons for the proposed changes
  • proposed changes to the protocol or other document (eg investigational medicinal product dossier), showing previous and new wording
  • supporting data for the change, including:

    • summaries of data
    • updated overall risk-benefit assessment
    • possible consequences for subjects already in the trial
    • possible consequences for the evaluation of results

You can make your submission using the Common European Submission Platform (CESP) or submit your documents as a single folder of separate files in PDF format. If it is impossible to submit a PDF version you can submit documents in MS Word format.

Label your CD securely as ‘Application for amendment’, with:

  • company name
  • EudraCT number
  • date sent

Send the CD to:

Information Processing Unit
Area 6
Medicines and Healthcare Products Regulatory Agency
151 Buckingham Palace Road
Victoria
SW1W 9SZ

Assessment process

We will assess your application within 35 days. Healthy volunteer trials and sponsor-determined phase I trials in non-oncology patients may qualify for a shorter assessment time (average 14 days). State in the heading of your covering letter if you think your trial is eligible.

Invalid applications

If your application does not meet the requirements it will not be assessed. You will be told the reasons why your application is invalid, which could include:

  • no proof of payment
  • incomplete notification of amendment form
  • required documents missing

Check the common errors seen at validation (PDF, 43KB, 1 page) to ensure you’re submitting a valid application.

For queries about electronic documents and submissions email RIS.CT@mhra.gsi.gov.uk.

Outcome of assessment

We will tell you the outcome of your application by post or by email if you are based overseas.

If your application is not successful we will tell you why and you may resubmit your application.

Fees

There is a single fee of £250 for changes that need assessment, regardless of the number of assessor disciplines involved in the assessment.

Make a payment to MHRA

You can pay online, by cheque or by BACs transfer.

When paying you should quote your EudraCT number in the ‘MHRA 1 reference/invoice number’ field.

For further information on how to pay fees contact the Cashiers Department on 020 3080 6507 or email: cashiers@mhra.gsi.gov.uk.

Change your contact details

You should send an email entitled ‘Change to Contact Details of the contact person for a CTA (Number XXXXX/XXXX/XXX-XXXX) – EudraCT Number XXXX/XXXXXX/XX’.

Email: ct.submission@mhra.gsi.gov.uk

The email must be sent as a signed and scanned attachment by the contact person listed on the application form and must include:

  • EudraCT number
  • CTA number
  • Protocol number
  • details of the previous contact person and/or contact details
  • details of the new contact person and/or contact details, to include:

The new contact person or details should be updated on the application form (which is part of your initial application form) and an updated XML should be included in the next submission of a substantial amendment so that the details can be uploaded into EudraCT.

If you want to change the sponsor or legal representative for your study you must submit a substantial amendment to MHRA. You can’t include any other changes with this amendment.

You can’t submit any other substantial amendments until you have confirmation from MHRA that the sponsor or legal representative has been changed.

If your want to change your sponsor you must include these additional documents with your submission:

  • a cover letter that includes the date of transfer of responsibilities
  • a letter on headed company paper from the current sponsor confirming the transfer of the study
  • a letter on headed company paper from the new sponsor confirming that they accept the role of sponsor for this study

During the assessment of your amendment you will receive:

  • a letter acknowledging receipt of the amendment
  • a letter confirming that the change has been registered and the old clinical trial authorisation (CTA) number has been closed on our system

Report an urgent safety issue

As a sponsor or trial investigator, you must act immediately if you find a safety issue during a clinical trial to protect subjects from any immediate threat to their health and safety.

Phone the MHRA’s Clinical Trial Unit on 020 3080 6456 to discuss the issue with a safety scientist, ideally within 24 hours. If we need more information a medical assessor will contact you.

You must then inform MHRA in writing within 3 days of the incident. MHRA will tell you how to do this when you speak to them, but it will usually be by email. Written notification in the form of a substantial amendment (annex 2) is also required.

What to report to MHRA

You must report all suspected unexpected serious adverse reactions (SUSARs) which happen during the course of the trial to MHRA.

You must report fatal or life-threatening SUSARs as soon as possible, but no later than 7 days after you are first aware of the reaction. Any additional relevant information must be sent within 8 days of the report.

You must report non-fatal or non-life-threatening SUSARs as soon as possible but no later than 15 days after you are first aware of the reaction.

You must report all UK-relevant SUSARs to MHRA.

The agency’s definition of ‘UK-relevant’ includes:

  • SUSARs originating in the UK
  • SUSARs originating outside the UK where the sponsor has an ongoing trial in the UK involving the same medicinal product

You must keep detailed records of all adverse reactions relating to a clinical trial. MHRA may require you to send copies of records if there is an investigation.

Further information is on the European Commission website.

Report a SUSAR in 1 of the following ways:

You will need to register your details with us before using the eSUSAR website. You should complete the eSUSAR registration form (MS Word Document, 44.5KB) and email it to esusar@mhra.gsi.gov.uk with the subject line ‘eSUSAR registration’.

Information that you need to include in a SUSAR report can be found on the European Commission website.

Submit development safety update reports (DSURs)

Your development safety update reports (DSURs) should take into account all new available safety information received during the reporting period.

The DSUR should include:

  • a cover letter listing all EudraCT numbers of trials covered by the DSUR, including any trials approved via the VHP process
  • an analysis of the subjects’ safety in the concerned clinical trial(s) with an appraisal of its ongoing risk/benefit
  • a line listing of all suspected serious adverse reactions (including all SUSARs) that occurred in the trial(s), including all SUSARs from third countries
  • an aggregate summary tabulation of SUSARs that occurred in the concerned trial(s)

Full details of what to include in a DSUR are on the European Commission website.

You can submit your DSUR using CESP or on a CD to:

Information Processing Unit
Area 6
Medicines & Healthcare Products Regulatory Agency
151 Buckingham Palace Road
Victoria
SW1W 9SZ

At the end of the DSUR reporting period the sponsor may assess the new safety information that has been generated and submit any proposed safety changes to the investigator’s brochure as a substantial amendment. This amendment should be supported by the DSUR and approved before the reference safety information (RSI) is changed.

The RSI for any investigational medicinal product involved in a clinical trial must stay consistent during each reporting period.

Suspend or terminate a trial

MHRA has the authority to make amendments to an authorisation or in certain circumstances suspend or terminate a trial. You can apply to MHRA to suspend or terminate your own trial.

Suspend a trial temporarily

If you suspend a trial temporarily you must notify MHRA and the Research Ethics Committee (REC) immediately or at least within 15 days.

The notification should be made as a substantial amendment using the notification of amendment form, clearly explaining what has been stopped and the reasons for the suspension.

Substantial amendments relating to temporary suspension and urgent safety measures must be submitted using CESP or as PDF documents on a disk to MHRA.

To restart a trial that has been temporarily suspended, you should make the request as a substantial amendment using the notification of amendment form, providing evidence that it is safe to restart the trial.

Terminate a trial

Complete the end-of-trial declaration form and include a brief explanation of the reasons for ending the trial. The form should be submitted using CESP or sent on a disk to the Information Processing Unit.

End of trial

A declaration of the end of a clinical trial should be sent to MHRA within 90 days of the global end of the trial.

It is not possible to submit amendments to the trial once the declaration form has been received.

End of trial study report

You must submit the end-of-trial study report to MHRA within 1 year of the global end of the trial. The trial officially ends when it is finished in all participating countries; don’t send the study report when only the UK part of the trial has finished.

You can submit your report using CESP or on disk, with 1 file for each document. All disks should be sent to the Information Processing Unit.

If a trial is terminated before the specified date of conclusion, the sponsor must notify MHRA and REC within 15 days of the date of termination.

Contact

For information about your submission contact the clinical trials helpline on 020 3080 6456 (Monday to Friday 8:30am to 4.30pm) or email clintrialhelpline@mhra.gsi.gov.uk.

For status and tracking enquiries you should call the Regulatory Information Service on 020 3080 7400 or email ris.ct@mhra.gsi.gov.uk.