How to Design a Clinical Trial Protocol

How to Design a Clinical Trial Protocol

June 22, 2021 By

A clinical trial protocol is a document that is designed to outline all details of a clinical trial. It is the main document referred to throughout the trial lifecycle and is arguably one of the most important documents in a clinical study – whether during the regulatory submission phase, or the execution of the trial itself. Some of the details required in a protocol include, but are not limited to: the trial design, primary and secondary outcomes, study population and sub-populations, eligibility criteria, adverse events, statistical analysis, and regulatory considerations/oversight. The protocol must be drafted ahead of a regulatory submission. In many cases, a protocol is written as a collaborative effort between the Sponsor of the clinical trial, the Contract Research Organization (CRO), and the study or site team. Input from the research/scientific, laboratory, clinic, data, and regulatory teams are integral to the creation of a protocol.

A protocol should be clear, concise, and well-planned. Some considerations for planning a clinical trial protocol involve the entire study team. It is very important to consider the time required for all assessments to be completed by the study staff as well as the participant(s). For outlining procedures that will take place during individual study visits, it is critical to ensure that the description of the flow of visits in the protocol makes sense. Ideally, the procedures to be conducted at each visit should be listed sequentially. This provides more linear guidance to the staff who will be conducting the trial. It will also help guide the creation of other documents required for clinical trials, such as Case Report Forms (CRFs) and the proposed monitoring plan.

As is the case with any other document or publication, appropriate reference annotation is essential. Reference styles may differ between organizations, but generally any widely accepted reference style that is used in scientific publications is appropriate to use in a clinical trial protocol. References are usually used in the Background section of a protocol, providing any details about previous research done on the investigational product or related substances. This section helps to lead the way to explaining why this clinical trial will further prove any previous hypotheses.

It is important to note that when designing a protocol, you want to set yourself up for success. When drafting one, always ask yourself, “How easy is it to deviate from this point?”. Protocol Deviations are sometimes necessary while conducting a clinical trial. Deviations can be major or minor, but they are important to document irrespective of their severity. In order to minimize deviations that may occur, a protocol must be carefully written in such a way that deviations will not be triggered easily. Some ways that this can be overcome include: ensuring staff that will be delegated by the Principal/Qualified Investigator (PI/QI) are assigned appropriately to their tasks outlined in the protocol, ensuring you give yourself a specified buffer time when deciding on timepoints for sample collection, and adding clauses that gives the PI/QI discretion to assess certain aspects on a case-by-case basis. Subject safety is of utmost importance in clinical trials and maintaining that safety while enrolled in a clinical trial is one of the main functions of the PI/QI’s duties.

Clinical Trial protocols are generally reviewed by a government regulatory body, as well as an independent ethics review board. Once a protocol is approved by both parties, this document cannot be changed in any way. Any changes made must be approved prior to implementation unless a participant’s safety is at risk. Always make sure you are using the most recently approved version of the protocol when conducting clinical trials.

Finally, I would caution against creating a clinical trial protocol that are rigid or limited in fashion and/or developed during a short time period. It is absolutely critical to ensure due diligence, making sure all relevant parties have had sufficient time to review for accuracy, flow, and feasibility – incorporating feedback received from all parties takes both time and critical-thinking. Input from the Sponsor, PI/QI, and other team members will prove invaluable. This feedback will help to create a robust, thorough protocol that meets regulatory and ethical research standards.

If you want to leave the protocol for your next clinical trial to the experts, dicentra offers services including protocol writing, protocol review, and handling the entirety of a regulatory submission for a clinical trial. Contact us today for more information!