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How to Review a Clinical Trial Protocol (Free Checklist Included)

by | Nov 8, 2023 | Clinical Research Careers, Clinical Trial Managers, Tips for Research Professionals, Tools for Research Professionals | 1 comment

Reviewing a clinical trial protocol can be overwhelming and time-consuming, but the protocol is a document that a study team needs to know inside and out.

The protocol can be updated through amendments, so a protocol review may happen several times throughout a trial.

Your protocol review will feel much more feasible with a good understanding of a protocol and the most critical areas to assess.

The three steps to reviewing a clinical trial protocol are assessing the essential sections, reviewing the entire protocol, and reading the informed consent template. To successfully review a protocol, you must have a list of the crucial sections and take notes throughout your review process.

What is a Clinical Trial Protocol and What is its Purpose?

A clinical trial protocol is a written document that describes how a clinical trial will be conducted. 

The purpose of a protocol is to:

  1. Communicate the intent and desired outcomes of a study
  2. Provide instructions for how to execute the clinical trial including drug or device administration
  3. Provide guidance on how to select and manage study participants including follow-up on safety events
  4. Ensure the integrity of the data collected

The protocol details the objective(s), design, methodology, statistical considerations, and organizational aspects related to the trial. In addition, it includes the background and rationale for the study and specific research questions the study is trying to answer. 

A study’s protocol keeps the study team, Sponsor, vendors, Institutional Review Board (IRB) or Ethics Committee (EC), and other regulatory personnel on the same page. 

All clinical trial protocols must adhere to the principles of Good Clinical Practice and receive approval before implementing.

What is a Protocol Amendment?

A protocol amendment is typically created if there is a change to the protocol that will affect the following:

  • Safety of the patients
  • Scope of the investigation
  • Scientific quality of the study

A protocol may also require an amendment if the information is unclear or missing. For example, the protocol may say that the patient needs to have three EKGs during their third office visit. If the three EKGs need to be precisely 30 minutes apart, but it is not specified in the protocol, a protocol amendment may be needed.

Another reason a protocol may require an amendment is if there is a change in inclusion or exclusion criteria. For example, the protocol may initially indicate that study participants must be women aged 25 to 40. However, during the study, the age group was expanded to age 25 to 50, which would require a protocol amendment.

PRO TIP: Many Clinical Trial Managers (CTMs) keep a running log of protocol changes needed. This way, when there is a protocol amendment, one amendment can capture multiple changes including administrative changes, which is much more efficient than needing numerous protocol amendments.

Typically, the CTM tracks the changes required in MS Excel and provides the information to the Sponsor or Medical Writer, who then writes the protocol amendment. 

Watch this short video to learn more about handling a protocol amendment as a CTM. 

When to Review Your Clinical Trial Protocol

As soon as a new approved clinical trial protocol is available, the Clinical Trial Manager, Clinical Research Associate (CRA), and other study team members should review the document. 

After completing the protocol review, study planning and organizing can begin.

If you join a study after it has started, one of the first things you should do is review the protocol. The protocol provides the background information you need to move forward successfully. 

CTMs are responsible for reviewing the clinical trial protocol at various times throughout the trial to help ensure the study stays in compliance and meets all expectations. 

How to Review Your Clinical Trial Protocol

Protocols can be hundreds of pages, so it’s easy to get lost in your clinical trial protocol review – or take more time than is needed. Also, you don’t want to miss reviewing an essential section. (Not all protocols are that long; the complexity of the trial typically determines the length.)

First and foremost, check to be sure you are reviewing the most current version of the protocol. 

Next, decide if you are more comfortable working with a hard copy or a file on your computer.

Then, look at the cover page; it contains a lot of information about the study. Here are some of the details that you may find on the cover page of the study protocol:

  • Protocol Title
  • Study Phase (I, II, III, or IV)
  • Open-Label?
  • Randomized?
  • Double Blind?
  • Multi-Center?
  • Single Center?
  • Study Sponsor
  • Version Number and Date

We created a list of key sections you’ll want to look for to make your protocol review less overwhelming and more productive. You can download the free checklist here. You can also review this protocol review tips video on the ClinEssentials YouTube channel for additional specifics on the essential sections noted within the free checklist. 

Throughout your review, take note of information you don’t understand; you may find your answers as you continue reading. Once you complete your review of the essential sections in the protocol, go back and review the entire document from start to finish. 

In addition, you want to review the trial’s informed consent template to learn about the study from the patient’s perspective. 

PRO TIP: If using a printed copy of the protocol, flag sections you will refer back to often with a sticky note such as Inclusion/Exclusion criteria, Prohibited Medications, Drug Administration, Safety Reporting and the Schedule of Events. 

Resources for Protocol Reviews (and more)

You should know your study protocol like the back of your hand. Make sure to always have an easily accessible electronic copy or a hard copy of the protocol to use as a reference.  

A clinical trial protocol is an essential document; detailed knowledge and proper reviews are crucial. Utilizing resources like this checklist will enable you to complete this task and set yourself up for ongoing success!

If you are interested in moving to a CTM role in the future, learn more about transitioning to the CTM role in this free downloadable guide.

If you are ready to take the next step in your career, we dive in deep on the topic of study protocols during the ClinEssentials CTM Training Course. If you are an aspiring or current Clinical Trial Manager, this course will help boost your understanding of the CTM role and your confidence to take on CTM responsibilities for all stages of a study. You can learn more about the CTM Training Course here

Tiffany Ashton, MAS, CCRA, has over twenty years of experience as a Clinical Research Professional. Tiffany is the Director of Operations for ClinEssentials, a consultant in the Clinical Trial Manager role, and the expert instructor for the CTM Training Course.

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