What is a clinical trial protocol?

A clinical trial protocol is a comprehensive plan that describes how the trial will be conducted. The Principal Investigator (PI) and the trial team must conduct the trial in accordance with the approved protocol.

The clinical trial protocol describes the scientific and medical rationale, objectives, design, and statistical considerations. It ensures the safety of the trial participants and the integrity of the data collected. The protocol serves as a blueprint to ensure standardisation. If someone were to repeat the study, they would be able to do so exactly by following the protocol.

What is included in a clinical trial protocol? 

• Title page: This is the initial point of reference, containing general information about the trial and administrative details.
• Introduction: Offering a contextual understanding, this section outlines the background and rationale behind the trial, clarifying the scientific basis and necessity. 
• Objectives/purpose: This segment clearly delineates the trial's goals. It specifies the precise objectives or hypotheses being investigated, providing a clear direction for the study.
• Trial design: This section details the trial's structure, including its type (such as parallel group, crossover, factorial, or single group), allocation ratio, and framework (superiority, equivalence, noninferiority, explanatory).  
• Selection and exclusion of participants: This outlines participant inclusion and exclusion criteria, ensuring the trial's integrity and relevance to the target population.
• Treatment of participants: Describing the interventions or treatments administered to participants, this section explains the procedures followed during the trial.
• Assessment of efficacy: This section identifies the methods that will be used to evaluate the effectiveness of the interventions under investigation, providing insights into the trial's outcomes. 
• Safety and reporting monitoring: This section details protocols for monitoring, reporting and assessing participant safety to ensure ethical standards are upheld throughout the trial. Provide guidelines for documenting and addressing adverse events; this section emphasises participant welfare and safety.
• Discontinuation of the study: This section identifies the criteria and safeguards for prematurely terminating the trial where there are ethical or safety concerns. 
• Statistics: Statistical methodologies and analyses are identified to ensure the robustness and validity of the trial's findings.
• Quality control and assurance: This section details measures to maintain the quality and integrity of trial procedures and data collection processes.
• Ethics: Addressing ethical considerations and ensuring compliance with ethical guidelines and regulations prioritises participant welfare and rights.
• Data handling and record keeping: Describing procedures for data collection, storage, and management ensures the accuracy and integrity of trial data.
• Publication policy: Clarifying policies regarding disseminating trial results and publishing findings promotes transparency and accountability.
• Project timetable/flowchart: Providing a visual representation of the trial timeline and workflow facilitates efficient project management and coordination.
• References: Citing relevant literature and sources provides context and supports the scientific validity of the trial.
• Supplements/appendices: Including additional materials or documentation, such as informed consent forms, study instruments, or regulatory approvals, enhances the completeness and comprehensibility of the protocol. Refer to the SPIRIT Checklist for further guidance on ensuring the inclusion of essential protocol components in interventional clinical trials.

Is a clinical trial protocol different to a trial project plan?  

A clinical trial project plan and a trial protocol are both essential documents in the planning and execution of a clinical trial, but they serve different purposes and contain distinct elements.

A clinical trial project plan serves as an operational roadmap outlining the practical and logistical considerations essential for effectively executing the trial. The project plan is a dynamic document that may need to be updated in response to operational, regulatory, budgetary, or other changes encountered during the course of a clinical trial. 

The clinical trial protocol is a comprehensive document that describes the scientific and medical rationale, objectives, design, and statistical considerations. It serves as a blueprint to ensure standardisation so that if someone were to repeat the study, they would be able to do so exactly by following the protocol.