Clinical Trials of Investigational Medicinal Products (CTIMP)
Study preparation requirements for clinical trials of investigational medicinal products
The chief investigator of a clinical trial has responsibility for the design, conduct and reporting of the trial. This includes ensuring the welfare of participants whilst in the trial, the safety of staff and that the trial is conducted according to good clinical practice and legal requirements.
All clinical trials need to undergo a risk assessment before initiation so that foreseeable risks and inconveniences can be weighed against the anticipated benefit for individual trial subjects and the general population as a whole.
A trial must only be initiated and continued if the anticipated benefits justify the risks.
Contact the Research Governance, Ethics & Assurance Team early in the planning process for advice on costs to be included in your funding application, such as:
- production, labelling and packaging of the trial medicines
- statistical services
- GCP monitoring and audit
- CTA application fee
- amendment fees
- code-breaking services
- archiving costs
Early in planning you need to:
- identify the supplier of your IMP, who should also supply an up-to-date investigator's brochure (for unlicensed IMPs), IMP dossier (if required), or summary of product characteristics (SmPC – for marketed drugs), and provide prompt updates on any safety issues that arise during trial conduct
- involve the Medical Sciences team early for support on agreements which need to be put in place for IMP supply and for the awarding of any educational grant.
If a pharmaceutical company is involved in the provision of their drug for your trial they may also wish to be involved in safety reporting.
You may wish to approach a clinical manufacturing organisation for supply of the IMP including packaging and labelling and randomisation services.
EudraCT is the European clinical trials database of all clinical trials. Registration is compulsory for every clinical trial with at least one site in the European community, and provides a unique identification number for the trial. You can do this online on the EudraCT website.
The CESP system allows for a single electronic submission for clinical trials to all European regulatory agencies as required. All clinical trial applications are to be made through CESP. This also applies to amendments and DSURs.
Initial registration
To register with CESP, please contact RGEA.Sponsor@admin.ox.ac.uk with a registration name (first name, last name) and preferred email address. This can be a generic email address monitored by multiple users and the name of the individual user or clinical trial.
Following your registration you will receive an email with:
- a link to the CESP web platform
- contact details and opening hours for the CESP support team
- your CESP username
To complete your registration, follow the link in the email to the CESP log-in page where you will be required to set your password. If you do not receive this email please check your junk email folder; the password link will time out and demands prompt action.
For details of registration and submission please refer to:
Clinical trial submission to MHRA should be made through the MHRA submissions portal. This also applies to amendments and DSURs.
To register and gain access to MHRA Submissions, please contact the Research Governance, Ethics & Assurance Team (for University of Oxford sponsored trials only). Please provide names and University email addresses of who you want registered. Once you have been registered by us, you will be sent an automated email with a link to the platform which you will need to action quickly as it is time limited. Access to the platform will then follow using your University single sign on.
For further guidance on how to submit once you have access please refer to the MHRA webinar training video: submitting via MHRA submission.
All studies falling into the category of CTIMPs require authorisation by the Medicines and Healthcare Products Regulatory Agency. Application is via the Integrated Research Application System (IRAS) and the Research Governance, Ethics & Assurance Team will be happy to advise.
You will need to pay a standard application fee and a fee for any amendments until trial completion.
Journals that follow the Guidelines released by the International Committee of Medical Journal Editors (ICMJE) require many studies to have been listed on an independent, free to access, validated, public register.
This includes:
- trials whose primary purpose is to affect clinical practice
- trials providing evidence of clinical effectiveness or adverse effects
- investigations of the biology of disease
- collection of preliminary data that may lead to larger clinical trials
- device trials
The trial must be registered before the first patient is recruited. Authors whose trial is unregistered will have to convince the editor that they had a sound rationale when they decided not to register their trial.
Acceptable registries include:
- clinicaltrials.gov, for which the University has an account. Registration cannot be created until all regulatory approvals are in place. Please email RGEA.Sponsor@admin.ox.ac.uk if you would like an individual user account, including the CI’s full name, title, work phone and email address.
- International Standard Randomised Controlled Trial Number Register (ISRCTN). There may be a charge for registration. Some funding bodies require ISRCTN registration.
If any third party (including commercial involvement, facilities or services from an NHS trust or other university) is involved, then contracts and agreements need to be in place prior to trial start. These include:
- supply of the Investigational Medical Product
- funding/educational grant
- laboratory and/or pharmacy services
- out-of-hours code breaking services
- emergency medical cover
- participation of other sites (in multicentre studies)
- collaborations
- material transfer
The Research Governance, Ethics & Assurance Team together with the Research Funding & Contracts Team, can help identify what agreements are required.
Whilst the University, as sponsor, is legally responsible for the overall conduct of your trial, the regulations allow for accountability for certain functions to be shared or delegated by written agreement.
Prior to trial start, the Research Governance, Ethics & Assurance Team will need to agree with you which functions it is appropriate to delegate to the chief investigator or other individuals/organisations.
Delegation of accountability for specific functions depends on the resources available for your particular trial and the level of experience and related training acquired.
The day-to-day running of your trial will involve other staff to whom accountability will be delegated by the chief investigator via a written legal agreement.
Staff accepting these accountabilities must sign the delegation log, which must be filed in the trial master file/investigator site file.
Delegation to additional sites will normally be through the contract/agreement between the University and the trial site.
The regulations require a trial master file (TMF) to be kept for a clinical trial.
It should be set up as soon as there are documents requiring filing. We recommend they are filed together, in a coherent format to enable ease of access and so they are readily available for GCP monitoring, audits or inspections.
The Guidelines for Good Clinical Practice (GCP) (Section 8) list particular requirements for the contents of a TMF. To aid compliance the following are available and can be adapted as required:
Design of a clear case report form (CRF) and a system for recording and storing data electronically are essential aids to GCP compliance.
Whilst many researchers have access to software specially designed for the construction of databases, this is not essential for producing a compliant database.
A database should:
- have a written specification (what it is intended to do) – to be filed in the TMF
- be secure but accessible by those authorised to do so
- have a clear audit trail (what data additions and amendments have been made, when and by whom)
- be validated (tested) as 'fit for purpose'
Templates:
Regulations require that each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task. This applies to the chief investigator and to any staff to whom accountability is delegated. The chief investigator is responsible for ensuring all staff are appropriately trained for their role.
Training includes the protocol, relevant SOPs and GCP training. All training must be recorded and records accessible for monitoring, inspection and auditing.
