Clinical Trials

The Research and Innovation Division can assist investigators through the Clinical Trials approval process and can advise investigators what is available in wide network of support at Great Ormond Street Hospital (GOSH) and the UCL Great Ormond Street Institute of Child Health (ICH).

Research involving a Clinical Trial with an Investigational Medicinal Product (CTIMP) in an interventional study falls under the EU Clinical Trials Directive (2001/20/EC) and is subject to The Medicines for Human Use (Clinical Trials) Regulations 2004. A clinical trial of investigational medicinal product cannot start until:

• Authorisation is granted by the MHRA (Medicines and Healthcare Products Regulatory Agency)
• Approval from Health Research Authority (HRA) Approval is obtained and NHS REC Approval has been granted where appropriate. A separate REC application is not required it’s done in the one application to the HRA  It also replaces the need for an NHS R&D Form] and
• A no objection letter from relevant R&D office or the NIHR Clinical Research Network is the final step for the study to commence  (confirming their capacity and capability to deliver the study.
  • Researchers wishing to conduct research in the NHS in Wales or Scotland, or Health and Social Care (HSC) in Northern Ireland, must obtain ‘NHS (or HSC) management permission’ (also referred to as ‘R&D approval’ or ‘R&D permission’) for each NHS/HSC research site.

The Division of Research and Innovation can assist investigators through the approval process and can advise investigators what is available in terms of support at GOSH and ICH.

A Clinical Trial of an Investigational Medicinal Product (CTIMP) is defined in the Medicines for Human Use (Clinical Trial) Regulations 2004 as:

Any investigation in human subjects, other than a non-interventional trial, intended:

• to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products,
• to identify any adverse reactions to one or more such products, or 
• to study absorption, distribution, metabolism and excretion of one or more such products, with the object of ascertaining the safety or efficacy of those products.

All CTIMPs require a Sponsor who takes responsibility for all aspects of the trial. If you are planning to carry out a CTIMP involving human subjects and would like to discuss GOSH sponsorship then please contact Clinical Trials team as per the contact details provided below:
Dr Vanshree Patel (Head of Governance, Clinical Trials and Contracts), 020 7905 2271 (x4-2271)

Ilyas Ali
Clinical Trials Manager
Ilyas.Ali@gosh.nhs.uk  

Subarna Sriskantharajah
Clinical Trials Coordinator
Subarna.Sriskantharajah@gosh.nhs.uk  

More guidelines and information on Clinical Trials (CTIMPs) are given in the following sections:

• Initial submission
• Trial conduct
• Trial end

The minimum following documentation should be provided to the Clinical Trials Manager before sponsorship of CTIMPs can be assessed.

• Draft/final protocol or trial proposal
• Details of trial funding
• Details of drug supply

A protocol is defined as “a document that describes the objectives, design, methodology, statistical considerations and organisation of a clinical trial”. The term protocol also refers to, successive versions of the protocol and protocol amendments. The clinical trial protocol should have a specific standard according to ICH Good Clinical Practice (GCP) guidelines. Please refer to the Protocol Template in standard operating procedures and forms subsection of this page which can be adapted for your Clinical Trial Protocol development. The Clinical Trials Team will provide support and advice to ensure your clinical trial protocol is Good Clinical Practice compliant. This is required before GOSH Sponsorship can be confirmed.

For CTIMPs, where GOSH is asked to act as the Sponsor or co-sponsor, we will carry out a CTIMP risk assessment by completing the risk assessment form which includes identifying risks related to protocol and its procedures and mitigating them. The Clinical Trials Team will complete the risk assessment with assistance from the Chief Investigator and the trial team as necessary.

We have an expert advisory panel to review CTIMP studies and consider Sponsorship by GOSH. Once a protocol has been agreed and a risk assessment has been completed, the Clinical Trials Team will arrange for your study to be reviewed by the Sponsorship Committee to discuss the risk elements. If the trial has high risk elements, individuals from the trial team may be invited to the meeting to present the trial in a format defined by the Committee or clarify the queries via email.

GOSH/ICH R&D office is responsible for keeping detailed records of all serious adverse events/reactions in clinical trials of investigational medicinal products where GOSH is the Sponsor or host organisation. For GOSH sponsored studies, the R&D office is responsible for reporting SUSARs to the Competent Authority (MHRA), Ethics Committee and other Principal Investigators according to Article 16(4) and Article 17 (1a, b and d) of the Clinical Trials Directive. For externally sponsored studies GOSH has a responsibility for patient’s safety as the hosting organisation.

All SAEs/SUSARs from GOSH sponsored and externally sponsored studies (where GOSH is a site) shall be reported to GOSH/ICH R&D Office within 24 hours of the notification of the event or within the timeframes specified for SAEs and SARs in your CTIMP protocol. Please refer to the Pharmacovigilance; Reporting and Recording of S/AEs SOP (6 - GOSH-ICH-05-CT06) in standard operating procedures and templates subsection on this page.

The R&D Department has a template Serious Adverse Events Reporting Form (Form 44 SAE_R_Reporting_Form) which you can use to report SAEs/SUSARs or Form 20 (Form 20: Report of Other Important Safety Issues)for any other important safety issues during the study conduct (Both can be found under standard operating procedures and templates subsection), you will need to email a copy of the signed form to the following email address:

• CTIMP.safety@gosh.nhs.uk 

It is a condition of the Clinical Trials Authorisation (CTA) from the MHRA that a Development Safety Update Report is submitted on each anniversary of issue of the CTA. This report should also be copied to the main Research Ethics Committee (REC) and the R&D Department. A Development Safety Update Report template is available for you to use, please email CTIMP.Safety@gosh.nhs.uk or Clinical trials manager to obtain a copy.

You may take appropriate urgent safety measures to protect clinical trial subjects from any immediate hazard to their health and safety. The measures should be taken immediately. You do not need to wait for Licensing Authority approval before implementing urgent safety measures.

The Chief Investigator should phone the Clinical Trial Unit at the MHRA and discuss the issue with a safety scientist immediately. The Chief Investigator should also inform the Clinical Trials Manager immediately and Trials Manager will notify the MHRA and the Ethics Committee, in writing, of the measures taken and the reason for the measures within three days.

A substantial amendment should be submitted subsequently to incorporate the changes made to the protocol or any other documents.

A substantial amendment is defined as an amendment to the terms of the protocol or any other supporting documentation that is likely to affect to a significant degree:

• the safety or physical or mental integrity of the subjects of the trial;
• the scientific value of the trial;
• the conduct or management of the trial; or
• the quality or safety of any investigational medicinal product used in the trial. 

The REC, MHRA and relevant R&D department must approve substantial amendments, before they are implemented (Where a project has HRA Approval and has been reviewed by a REC, the substantial amendment only needs to be reviewed by REC). Some substantial amendments only require authorisation by the REC, such amendments do not have to be notified to the MHRA. Where the substantial amendment requires authorisation by the MHRA and the REC, submission to both bodies is still required.

MHRA do not need to be notified of non-substantial amendments but the sponsor should be notified including when it was implemented, and records should be kept in the Trial Master File. Other (non-substantial) amendments: Where the lead NHS R&D office is in England you should submit the amendment to hra.amendments@nhs.net and for studies where the lead NHS R&D office is in Northern Ireland, Scotland or Wales the categorisation will be undertaken by the lead nation.Please refer to the SOP(10 - GOSH-ICH-07-CT10) in the standard operating procedures subsection. The Clinical Trials Manager will review all the amendment documents before you submit to Ethics and MHRA.

Please inform R&D promptly if you decide to halt a trial temporarily. The MHRA and Ethics Committee should be notified immediately and at least within 15 days from when the trial is temporarily halted. The Trials Manager will assist you in the notification that should be made as a substantial amendment using the notification of amendment form and clearly explain what has been halted (e.g. stopping recruitment and/or interrupting treatment of subjects already included) and the reasons for the temporary halt.

To restart a trial that has been temporarily halted, the Trials Manager will assist you to request the reopening as a substantial amendment using the notification of amendment form and providing evidence that it is safe to restart the trial.

If you decide not to recommence a temporarily halted trial or decide to terminate a trial before the date specified for its conclusion please inform R&D at the earliest as MHRA and Ethics Committees should be notified within 15 days of this decision, using the End of Trial Declaration form available from the EudraCT: European Clinical Trials website and including a brief explanation of the reasons for ending the trial.

The definition of the end of the study should be clearly defined in the protocol and any change to this definition should be notified as a substantial amendment. In most cases, it will be the date of the last visit of the last participant or the completion of any follow-up monitoring and data collection described in the protocol.

Final analysis of the data (following ‘lock’ of the study database) and report writing is normally considered to occur after formal declaration of the end of the study.

The Clinical Trials Team should be notified promptly of the trial completion and the Trials Manager will notify the MHRA and Main REC within 90 days of the end of the Clinical Trial by completing the End of Trial Form (Where a project has HRA Approval and has been reviewed by a REC you need only inform the REC when your study has ended)

Regulation 29A of the Medicines for Human Use (Clinical Trials) Regulations 2004 [Statutory Instrument 2004/1031], as amended by Statutory Instrument 2006/1928, contains a requirement for the notification of "serious breaches" of GCP or the trial protocol.

“The sponsor of a clinical trial shall notify the licensing authority in writing of any serious breach of -

• (a) the conditions and principles of GCP in connection with that trial; or
• (b) the protocol relating to that trial, as amended from time to time in accordance with regulations 22 to 25, within 7 days of becoming aware of that breach.

For the purposes of this regulation, a “serious breach” is a breach which is likely to effect to a significant degree –In case of any suspected breach of GCP or protocol, the Chief Investigator or Principal Investigator should complete Form F20: Report of Other Important Safety Issue, and send it to the GOSH/ICH R&D Office or CTIMP.safety@gosh.nhs.uk  for review. All suspected serious breaches MUST be notified to the GOSH/ICH R&D Office within 24 hours of the breach being identified. The Chief Investigator and the GOSH/ICH R&D office clinical trials team should evaluate the incident to confirm whether the breach fulfills MHRA definition of a serious breach. If the incident is identified as a serious breach, then the Joint R&D office clinical trials team will compile all the supporting documentation pertaining to the breach and submit to MHRA within 7 days of assessing the event as a serious breach. The SOP, (12 - GOSH-ICH-11-CT12) for serious breach can be found under standard operating procedures subsection.

• (a) the safety or physical or mental integrity of the subjects of the trial; or
• (b) the scientific value of the trial.”

The publication policy of a Clinical Trial should be addressed in the protocol. The Chief Investigator should provide a summary of the Clinical Trial Report within one year of the end of the trial to the Clinical Trials Team and this will be submitted to the main REC.  The Chief or Principal Investigator and or the Sponsor are also responsible for uploading the end of trial summary results to EudraCT as per the commission’s guidelines on posting and publication of result-related information. You don’t need to submit this clinical trial summary report to the MHRA as well however you must send a short confirmatory email to CT.Submission@mhra.gsi.gov.uk once the result-related information has been uploaded to EudraCT, with ‘End of trial : result-related information: EudraCT XXXX-XXXXXX-XX’ as the subject line.

More information on conduct of CTIMPs can be found at HRA and MHRA GOV UK websites:

http://www.hra.nhs.uk/about-the-hra/our-plans-and-projects/assessment-approval/

https://www.gov.uk/guidance/clinical-trials-for-medicines-manage-your-authorisation-report-safety-issues#end-of-trial