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Oxford University Hospitals NHS Foundation Trust
Research and Development

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Clinical trial planning

Clinical Trial Protocol development

A Clinical Trial Protocol is a document that describes in details the objectives, design, methodology, statistical consideration and organisation of a trial. The Clinical Trial Protocol is one of the essential documents required for a Clinical Trial and it is important that this is developed early on in the study preparation process. Although you may have prepared a Clinical Trial Protocol during preparation for funding application, there are additional aspects that you need to consider for a Clinical Trial.

The R&D Department has produced a generic Clinical Trial Protocol template which can be adapted to suit the Clinical Trial Protocol development and review process for your particular trial or department.

Specific funding requirements

All research should be fully funded and not subsidised by the NHS; there are many avenues open to researchers for applying for research funding.

The funder of the research can be a separate organisation from the Sponsor, and there can be multiple funders and multiple sponsors. You should contact OUH R&D Department as early as possible in the planning of your Clinical Trial of an Investigational Medicinal Product (CTIMP) to ensure that, firstly, the funding application is appropriately costed, and then costs and payments are identified where they need to flow through to clinical departments, or to other trusts if it is a multicentre study.

Examples of costs are:

  • production, labelling and packaging of the trial medicines
  • statistical services
  • GCP monitoring and audit
  • CTA application fee
  • amendment fees
  • code-breaking services
  • archiving costs.

Sourcing the Investigational Medicinal Product (IMP)

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 medicines with a marketing license, 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.

You may wish to approach a Clinical Manufacturing Organisation for supply of the IMP including packaging and labelling and randomisation services.

  • Involve the OUH contract team early for support on agreements which may need to be put in place for IMP supply, generation of reports (i.e. DSUR) and for the awarding of any educational grant.

European Clinical Trials Database of all clinical trials (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 for the trial, the EudraCT Number.

Clinical Trials Authorisation (CTA)

All studies that fall into the category of CTIMPs require authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA). Application is via the Integrated Research Application System (IRAS) and OUH R&D Department will be happy to advise.

Information regarding the submission process can be found on the MHRA website.

You will need to pay a standard application fee to the MHRA and a fee for any amendments submitted after the initial approval until trial completion.

Protocol registration

Most journals require many studies to have been listed on an independent, free to access, validated public register.

These include:

  • 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.

Acceptable registries include:

Agreements

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 Medical device
  • funding / educational grant
  • laboratory and/or pharmacy services
  • out-of-hours code breaking services
  • emergency medical cover
  • participation of other sites (in multicentre studies).

OUH R&D can help identify what agreements are required. The OUH contract team will help put these in place.

Delegation of Sponsor functions

Whilst the Trust, 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, OUH R&D 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.

Delegation within the Study Team

The day-to-day running of your trial will inevitably involve other staff to whom accountability is delegated by the Chief / Principal 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.

Trial Master File

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. R&D 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 Guideline for Good Clinical Practice (GCP) (Section 8) lists particular requirements for the contents of a TMF.

A GCP compliant Trial Master File contents page is available, and can be adapted as required. Please see our documents page.

All study documents should be version controlled by number and date.

Standard Operating Procedures

The Clinical Trial Regulations require you to have Standard Operating Procedures (SOPs) in place prior to the start of the study. These should cover the range of activities involved in the study conduct and are designed to ensure that practice is standard, regardless of who is carrying out the activity. Staff involved in the study should have been trained in the activities for which they are responsible and a clear concise SOP should give guidance as to how to perform an activity to anyone unused to that particular procedure.

The OUH R&D Department has a range of template SOPs, including an SOP Template.

These SOPs have been designed to be adapted/adopted by individual investigators. R&D staff will be able to identify which SOPs are required for your study.

If you are planning to adapt/adopt any of the R&D template SOPs, please contact us so that we can inform you should there be any major changes to them in the future.

Data management and Case Report Form design

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 to authorised users
  • have a clear audit trail (what data additions and amendments have been made, when and by whom)
  • be validated (tested) as 'fit for purpose'.

The following templates are available:

Training

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 / Principal 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.

OUH R&D and the Clinical Trials and Research Governance (CTRG) Team jointly organise GCP training days on a regular basis. Contact the CTRG administrator for details.

In addition, an online GCP course is available free to employees of OUH and the University of Oxford, or anyone working on a study sponsored or hosted by either organisation.

OUH requires that staff refresh their GCP training every three years.

Clinical trial set-up meeting

Even though OUH is sponsoring the research, the Trust must still formally approve the clinical trial - please refer to the applying for NHS permission section for more information.

After Trust Approval has been given, and only for clinical trials sponsored by OUH, the study will be officially initiated by a member of the R&D team. At this meeting issues relating to the conduct of the trial can be discussed, for example:

  • Delegation of Authority to the Chief Investigator
  • Investigational Medicinal Product (IMP) storage and dispensing
  • training undertaken
  • consent procedures
  • safety reporting
  • monitoring arrangements.