Initial concept to submission
| Please note that the CTRG pages are currently under development. If you have any questions please contact elaine.chick@admin.ox.ac.uk |
- Sponsorship
- Specific Funding Requirements
- Protocol Development
- Participant Information Leaflets and consent forms
- Sourcing your Investigational Medicinal Product (IMP)
- Insurance and Indemnity
- EudraCT Number
- Clinical Trials Authorisation (CTA)
- Ethics Application
- NHS Permissions
Sponsorship
The Sponsor
- takes legal responsibility for initiation and management of the study
- provides insurance for the study
- is required for all clinical studies not just trials
- is not necessarily the funder. Many funding bodies are unable to provide sponsorship
The University usually assumes Sponsorship when a University employee has designed the study and is acting as the Chief Investigator. The University must actively consent in writing if it is to act as Sponsor.
If you would like the University to sponsor your study, please contact CTRG as early as possible. As a minimum:
- at the time of funding application for Clinical Trials of an Investigational Medicinal Product.
- at least 5 working days before submission of an ethics application for all other clinical research.
CTRG will need the following documents:
IRAS full dataset and site-specific information forms, see https://www.myresearchproject.org.uk/Signin.aspx - download instructions  (628kb) |
| Detailed Protocol |
| Participant Information Leaflet |
| Informed Consent Form |
| Principal/Chief Investigator CV (NRES format) |
| GP Letter (if applicable) |
| Advertisement(s) including texts of email or radio adverts (if applicable) |
| Confirmation of Funding |
| Independent peer review, if applicable (i.e. if you do not already have an independent review as part of your funding application or project development. A template is available.) |
CTRG will review documentation prior to ethics submission and ensure that any insurance issues are addressed.
Ongoing sponsorship is subject to the following:
- All substantial amendments are approved by CTRG before submission to a REC or the MHRA
- Non substantial amendments including changes in end date, recruitment numbers and sites are notified to CTRG
- All Annual Progress Reports, Development Safety Update Reports (Trials only) and End of Trial/Study notifications must be copied to CTRG
Specific Funding Requirements
You should contact CTRG as early as possible in the planning of your Clinical Trial. They can advise on additional costs to be incorporated into your funding application, for example:
- Production, labelling and packaging of the study medicines
- Statistical services
- GCP monitoring and audit
- CTA application fee
- Code-breaking services
- Archiving costs
Protocol Development
A protocol is one of the essential documents required for a Clinical Trial. It describes in detail the objectives, design, methodology, statistical consideration and organisation of the trial. It is important that this is developed early on in the trial preparation process. Although you may have a protocol prepared for a funding application, there are additional aspects that you need to consider before submission to regulatory bodies. CTRG have produced an SOP Template for Study Protocol Development and Review (52kb) that can be adapted to suit your particular trial or speciality.
GCP Compliance
Your study protocol must comply with the requirements of the Clinical Trials Regulations. A GCP-compliant Clinical Trial Protocol Template (56kb) has been designed to ensure all aspects of the trial procedures have been considered, including the requirements for protocols from the Declaration of Helsinki (2008, clause 14). CTRG are happy to review your protocol for compliance and to give advice where it is needed.
Alternatively, you can refer to Section 6 of the ICH Guidelines for Good Clinical Practice (GCP) 
(380kb) for an outline of the requirements.
Peer review
If the research study has not been reviewed by the funder via a competitive process to ensure quality then you must provide an independent peer review: Independent peer review template (110kb)
Statistical review
The Centre for Statistics in Medicine may be willing to give you support if you do not have a statistician within your department.
Pharmacy Review
If you are planning to use an NHS pharmacy, then they should be included in the protocol review.
Document Control
You will need to ensure document control throughout the review procedure. CTRG have an SOP Template for Document Control (56kb), which can be adapted to suit your study or department.
Safety Reporting
This is one of the most important aspects of a Clinical Trial protocol. Consider whether the burden of reporting can be reduced without compromising safety:
- If your trial uses a licensed medicine, do you need to gather data on non-serious adverse events?
- If there are foreseeable serious adverse events, e.g. due to disease progression, can these be documented in the protocol to avoid the need for immediate reporting?
In both cases they must be clearly stated in the protocol approved by the MHRA and REC.
The safety section in the CTRG protocol template provides guidance on this and the CTRG team are happy to advise.
The Regulations require that all Serious Adverse Events (SAEs), unless excluded in the protocol, are reviewed by an appropriate Safety Monitoring Committee. If there is no trial-specific or department-specific Safety Monitoring Committee, CTRG may be able to make arrangements for your SAEs to be reviewed by the Oxford University Hospitals NHS Trust/University of Oxford Trials Safety Group (TSG). An SOP Template for Safety Reporting (96kb) is available.
Participant Information Leaflets and consent forms
It is important that the information given to participants, before obtaining their written informed consent to take part, is clear and concise. NRES (National Research Ethics Service) provides detailed guidelines, use of which will avoid unnecessary delay at sponsor and ethics review. The guidelines are updated from time to time so it is important to use the current version.Sourcing your Investigational Medicinal Product (IMP)
Early in planning you need to:
- Identify the source of your IMP who should also supply an up-to-date Investigator's Brochure (for unlicensed IMPs), IMP Dossier (if required), and provide prompt updates on any safety issues that arise during trial conduct. 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. Alternatively, you may wish to approach a Clinical Research Organisation for supply of the IMP including packaging and labelling and randomisation services.
- Involve Medical Research Services early for support on agreements which need to be put in place for IMP supply and for the awarding of any educational grant.
Insurance and Indemnity
For most studies, CTRG can confirm indemnity within the letter of Sponsorship. However, certain categories of trials and studies must be referred to the University insurance office for individual consideration. CTRG can do this for you. These are any research involving:
| Children under 5 years old |
| Investigation of processes of conception/contraception |
| Participants who are pregnant |
| Participants from outside the UK |
| Administration of drug/device/vaccine which has been designed, developed or manufactured by the University
|
| Any genetically engineered product |
Unless your study is on the CTRG database, indemnity is not assured. It is important that both the ethics application form and the Participant Information Leaflet include the correct indemnity statements. This is assessed individually on review of the study or trial. CTRG will advise on the appropriate wording.
EudraCT Number
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, the EudraCT Number. You can do this online at https://eudract.emea.europa.eu/.
Clinical Trials Authorisation (CTA)
All studies falling into the category of Clinical Trials require authorisation by the Medicines and Healthcare products Regulatory Agency. Application is via the Integrated Research Application System (IRAS) and CTRG will be happy to advise. An SOP Template for Preparation of a Clinical Trial Authorisation (51kb) is available for your use.
You will need to pay a standard application fee and an annual fee until trial completion.
Ethics Application
The Integrated Research Application System (IRAS) is used for all new ethics applications.
Clear guidelines are provided by NRES (National Research Ethics Service) on how to complete the form. CTRG staff will be happy to give you advice. Question-specific guidance is available on the IRAS website.
IRAS is a single form-filling system for applying for the relevant approvals from the following review bodies:
| Administration of Radioactive Substances Advisory Committee (ARSAC) |
| Gene Therapy Advisory Committee (GTAC) |
| Medicines and Healthcare products Regulatory Agency (MHRA) |
| Ministry of Justice |
| National Offender Management Service (NOMS) |
| NHS / HSC research offices |
| NRES/ NHS / HSC Research Ethics Committees |
| National Information Governance Board (NIGB) |
The forms are web-based and can be worked on repeatedly prior to submission. Documents to submit are itemised on a checklist provided on IRAS. These include:
| The protocol |
| Participant Information Sheet |
| Informed Consent Form |
| GP Letter (if any) |
| Advertisement (if any) |
| Sponsorship Letter (which includes a statement on indemnity) |
| Peer review |
| Study type specific documents such as questionnaires |
Once CTRG have approved your application you will need to book a slot for review by an ethics committee. You will be given an REC reference to add to your forms. CTRG will need this reference to issue a letter of Sponsorship and Indemnity approval and the signature page from your ethics application form. Please note that the final forms (without the DRAFT watermark) are generated on the IRAS site via a 'Submission' tab.
CTRG have produced an SOP Template for Ethics Committee Applications V3.1 (51kb) that can be adapted to suit your particular study.
NHS Permissions
If your study involves recruitment of staff or patients from an NHS Trust, or uses Trust facilities, you will need to get approval from the relevant R&D Department. A Site Specific Information (SSI) Form must be generated on IRAS and sent to the NHS Trust R&D office.
Co-ordinated System for NHS Permissions (CSP)
You can use CSP to gain NHS permission if your study
- is eligible for the NIHR CRN Portfolio. You need to complete a short Portfolio Adoption Form (PAF) via IRAS, for which you should receive a response within two working days; or
- is adopted by the Comprehensive Clinical Research Network, the Primary Care Research Network or one of the six Topic-specific Clinical Research Networks;or
- is NIHR-funded through Biomedical Research Centres (BRCs), Biomedical Research Units (BRUs) or Collaborations for Leadership in Applied Health Research and Care (CLAHRCs)
Further information about eligibility and the application process can be found on the NIHR CSP website.