Managing your Trial
The following section will provide guidance to Cardiff University employees in managing Clinical Trials which are sponsored by Cardiff University.
The Clinical Trials Toolkit website is also a useful resource, including interactive “route maps” to help guide researchers through trial management processes.
The information below is based on the ‘managing your trial’ route map. The processes 3-13 may not apply to all Clinical Trials.
- 1. Trial Begins
- 2. Consent and Recruitment
- 3. Safety Reporting (Pharmacovigilance)
- 4. Progress Reporting
- 5. Management and Monitoring
- 6. MHRA Inspection
- 7. Audit
- 8. Addition of New Sites
- 9. Substantial Protocol Amendment
- 10. Urgent Safety Measures
- 11. IMP Management
- 12. Good Clinical Practice Training
- 13. Insurance/Indemnity
- 14. End of Trial
- 15. Archiving
A trial should not commence until RACD has issued a 'Sponsor approval to commence’ letter. The approval to commence letter will be issued after a Trial Initiation Visit has taken place. The aim of the visit is to ensure that all relevant approvals and documentation are in place prior to the commencement of a trial. For further information on the procedure for obtaining Sponsor approval to commence please refer to the SOP: Approval to commence a CTIMP. To arrange a Trial Initiation Visit please contact the Research Governance Team.
For further information please refer to the Clinical Trials Toolkit 'Are you ready to start checklist'
A trial participant, legally, must give informed consent, before he or she can be recruited into a trial. More information about informed consent can be found within Cardiff University Research Ethics web pages. The National Research Ethics Services (NRES) have also produced a document summarising the statutory requirements for informed consent for Clinical Trials recruitment purposes entitled Informed Consent in CTIMPs.
The Trial Protocol should detail the recording and reporting requirements for Adverse Events
-Reporting of Suspected Unexpected Serious Adverse Reactions (SUSAR)
Any SUSAR which is fatal or life-threatening should be recorded and reported to the MHRA and ethics committee within 7 days of when the Sponsor was first aware of the SUSAR. Within 8 days of a report, any additional relevant information should be sent to the MHRA. If non-fatal or life-threatening SUSARs occur, the MHRA and relevant ethics committee should be notified within 15 days. This responsibility is normally delegated to the CI.
Further guidance and template forms for Adverse Event reporting are available below:
- SOP for the Managing and Reporting of Research Related Adverse Events in CTIMPs
- Template SOP for Adverse Event Reporting
- Template SAE Report Form
- Investigator Template for Recording Adverse Events
- Annual safety report
For each IMP tested, the Sponsor must provide the MHRA and ethics committee with an annual safety report. The report should describe all new safety information relevant to each clinical trial and IMP tested. This responsibility is normally delegated to the CI. The annual safety report should include:
- An analysis of the subjects’ safety in the clinical trial(s) with an appraisal of its ongoing risk: benefit.
- A listing and summary tabulation of all suspected serious adverse reactions (including all SUSARs) that occurred in the Trial, including all serious adverse reactions from third countries.
Further information on what to include in an Annual Safety Report can be found in Section 5.2 of: Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use-April 2006
The Research Governance Team will notify the CI when the annual safety report is required by the MHRA and ethics committee. For further information please refer to the Summary of Clinical Trial Regulations and the Medicines for Human Use (Clinical Trials) Regulations 2004.
Progress reports will be required annually by the relevant ethics committee starting 12 months after the date that the favourable opinion was given. A copy of this report should also be submitted to RACD. Progress reports should be submitted annually until the end of the Trial. A progress report form and further information is available on the NRES Website.
Please note, there may be additional reporting requirements to funding bodies and R&D offices.
Monitoring requirements will have been determined by the Risk Assessment Form completed prior to trial commencement.
- Risk Assessment Form (RAF)
At the protocol development stage, a RAF form should have been completed. This may be used to plan the details of trial management and the approach to, and extent of, monitoring during the trial. These plans should be documented, together with the risk assessment, such that the management strategy is both transparent and justified. This documentation is intended not only to facilitate the management of the trial but also to help prepare for external audit.
- Trial management groups (TMG)
TMG meetings, including Independent Data Monitoring Committee and Trial Steering Committee, should be documented to facilitate the management of the trial and help prepare for an MHRA inspection and other external auditors.
Please visit our MHRA Inspection web pages for further guidance.
The Research Governance Team will arrange audit/monitoring visits to ensure that:
- the rights and well-being of human participants are protected
- conduct of trial is compliant with the approved protocol, with ICH GCP and with regulatory requirements.
The nature and extent of the audit/monitoring visits will vary depending on the type of research being conducted. The Sponsor will review the Trial Master File (TMF) using the and review the subject file to ensure that all essential trial documentation is being stored. Following the Monitoring visit, the Sponsor will produce a report and if necessary provide a list of actions for completion.
The process for the audit/ monitoring visit (for Clinical Trials sponsored by Cardiff University) is described in the Sponsor Monitoring Visit SOP
The addition of a new site will be treated as a substantial protocol amendment. The following actions are required
-Notify RACD: Inform the Research Governance Team
-Notify MHRA: The addition of new sites should be sent to the MHRA as a substantial protocol amendment but for NOTIFICATION only. There is no requirement to wait for a response from the MHRA, but your submission will be acknowledged. For further information, please visit the MHRA Website
-Notify REC: Apply to the REC for site-specific assessment for the addition of a new site. Please refer to the NRES Website for more information.
-Notify R&D: NHS R&D approval is required for each new site.
An individual must not conduct the Trial other than in accordance with: the protocol; the terms of the request for authorisation from the MHRA; and with the ethics committee opinion. A protocol amendment to a Clinical Trial requires the CI to notify the MHRA, ethics committee and Sponsor. Only after approval has been granted by the MHRA and ethics committee may the amendment be made.
According to the Regulations a substantial amendment to a Clinical Trial means an amendment which is likely to affect to a significant degree any of the following:
-the safety, physical and/or mental integrity of the participants;
-the scientific value of the Trial;
-the conduct or management of the Trial;
-and the quality and safety of the Investigational Medicinal Product (IMP).
The Clinical Trial Regulations state that the MHRA and ethics committee will give written notice within 35 days, specifying reasons for accepting/ not accepting the amendment. For further information on submitting a substantial amendment please refer to the
Version Control- The Research Governance Team must be notified about any amendments to study documentation.
If protocol amendments are made which include a newer version of the protocol, GP letter, and patient invitation/information letter, the Research Governance Team recommend that older versions are retained in the TMF with a diagonal line crossed through the front page with ‘superseded by version, on date’ written at the top of the document. A Version Control Log is available for you to use. Information on record can be found in Cardiff University Governance and Compliance web pages.
It must be noted that all correspondence to and from the MHRA and NRES should be retained in the Trial Master File and an additional copy sent to RACD.
If, during the trial, urgent safety measures need to be taken, the Sponsor, CI or PI may take the appropriate action in order to protect Clinical Trials participants against any immediate harm. In such cases the CI should inform the Sponsor, MHRA and relevant ethics committee in writing within 3 days of the event occurring by submitting a substantial amendment. The substantial amendment should include: a covering letter detailing the measures taken; the reason for them and the medical assessor contacted; a Notification of Amendment form; and supporting documentation. Guidance on how to submit a notice of substantial amendment is available on the NRES Website.
IMP management requirements should be detailed in the Protocol and trial agreements and retained in the TMF. IMP management should be discussed with and agreed by Pharmacy prior to submission to MHRA.
An individual must not conduct a Clinical Trial or perform functions of the Sponsor other than in accordance with the principles of GCP. If the Trial is conducted at more than one site, the Sponsor may delegate responsibility for duties to an appropriate individual at a specific site. For more information, please refer to:
- Good Clinical Practice Directive (Directive 2005/28/EC)
- International Conference on Harmonisation Guidance on Good Clinical Practice (Topic E6) (CPMP/ICH/135/95)
GCP Training must be completed by all members of a Trial team including the CI/PI identified on the Trial Delegation. GCP Training should be renewed every two years.
Indemnity/ Insurance letters will need to be reissued every year and these letters will be provided by the Research Governance Team. If any substantial amendments to the protocol have been made, this may affect the insurance. For more information please contact the Research Governance Team.
Please visit the End of Trial web pages for further guidance.
The TMF and Trial Subject File must be stored in an appropriate and secure central location. For more information please refer to the Cardiff University’s Governance and Compliance Division can provide further information on archiving, record management and off site storage arrangements.