A protocol is defined in the Part 1(2) of The Medicines for Human Use (Clinical Trials) Regulations 2004 as: “A document that describes the objectives, design, methodology, statistical considerations, and organisation of a clinical trial”
The protocol also provides information on the background and rationale for a trial and outlines the study plan for that trial. The plan must be carefully designed to safeguard the health and safety of the participants, as well as answer specific research question(s). The protocol describes:
- the type of participant
- the schedule of tests
- medications and dosages
- the duration of the trial
- and should include a definition of the ‘end of the trial’ (see End of Trial Declaration station).
Protocols (and many other documents produced as part of a trial) should be controlled documents; version numbered and dated using a formalised convention.
Involvement of patients and the public (PPI) helps to shape fundamental aspects of the protocol to ensure it takes into account the needs of participants. INVOLVE have a number of helpful examples which demonstrate the impact of PPI in research. Useful information and resources about PPI can be found in the Trial Planning & Design station.
The NIHR Research Design Service (RDS) may provide support relating to aspects of protocol development such as trial design, choosing appropriate outcome measures and statistical input for researchers based in England.
To support researchers to develop high quality protocols, the Health Research Authority have produced protocol guidance and a template to assist organisations and individuals to improve the consistency and quality of their CTIMPs. The template is in line with regulatory requirements and the SPIRIT guidelines. Although the template is not mandatory, it contains all the elements that review bodies wish to consider, so protocols which have regard for the guidance and template are less likely to raise queries that can cause delays. A consideration of section 6 is useful when preparing funding applications and will facilitate the development of the protocol if funding is awarded. It is also worth noting that many research funders have specific requirements for protocol content and presentation that should be considered.
For non-CTIMP research, it is good practice for the protocol to include as much of the information in the topics/sections of ICH GCP E6 and the SPIRIT checklist, as relevant.
Both SPIRIT and the NIHR HTA Programme endorse the COMET database which contains information on published and ongoing core outcome set studies, and is regularly updated.
DIRUM is an open-access database of resource-use questionnaires for use by health economists involved in trial-based economic evaluations. DIRUM also provides a repository of methodological papers related to resource use and cost measurement.
Information on protocol review and signoff can be found in the Final Protocol station.
- Unique Trial Number station
- EudraCT Number station
- Final Protocol station
- Substantial Amendment station
- SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) is an international initiative that aims to improve the quality of clinical trial protocols
- The Research Support Services Framework: In England, NHS organisations that sponsor trials, conduct activities in line with the RSS Framework. Key document: RSS Framework-Annex5-S03-Ensure study protocol is managed (May 2011)
- Recommendations for the design of MAMS (multi-arm multi-stage) trials
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- Trial Planning & Design
- Within the scope of the Clinical Trial Regulations?
- Risk Assessment
- Protocol Development
- GCP & Serious Breach Reporting
- Trial Management & Monitoring
- Trial Documentation
- Trial Supplies
- R&D Consultation
- Funding Proposal
- Peer Review
- Funding Secured
- Trial Master File
- Unique Trial Number
- EudraCT Number
- Confirm Sponsor
- Feasibility & Investigator Selection
- Contracts & Agreements
- Final Protocol
- CI Checklist Before Seeking Approval
- CTA Submission
- Ethics Submission
- R&D Submission
- Permissions & Approvals Obtained
- Final Trial Management Documentation
- Trial is Abandoned
- Trial Begins
- Informed Consent
- Safety Reporting
- Progress Reporting
- Ongoing Management & Monitoring
- MHRA Inspection
- Addition of New Sites & Investigators
- Substantial Amendments
- Urgent Safety Measures
- Temporary Halt or Early Termination
- Trial does not Recommence
- End of Trial Declaration
- Statistical Data Analysis
- Clinical Trial Summary Report
- Dissemination of Results
Key to Symbols
Demonstrates processes that can be done in parallel
Demonstrates that not all processes will apply to all trials
|Standard Process||Legal Requirement||Good Practice|
|Specific for trials within Directive's scope|
|Relevant to all trials|