How to Write Site-Friendly Protocol Amendments in Clinical Trials

Clinical trial protocol development and maintenance are some of the most critical steps in the lifecycle of a research study. One of the most common (and important) maintenance pieces is the rollout of protocol amendments. 

The StudyTeam platform contains functionality to display aspects of the protocol – such as I/E criteria and visit schedules – from all relevant protocol versions. OneStudyTeam has deep expertise in assessing clinical trial protocols and protocol amendments, and implementing the relevant changes within StudyTeam so sites and sponsors can easily add, track, and assess data from the correct protocol version(s) as they manage and monitor recruitment and enrollment.

What are protocol amendments in clinical trials?

Protocol amendments in clinical trials are versions of the protocol that have been revised to implement changes such as updating I/E criteria, clarifying points of confusion, and adding or removing required study procedures. Nearly all clinical trial protocols we work with at OneStudyTeam will undergo at least one amendment throughout the life of the trial, with some undergoing as many as five, ten, or more. 

How to write site-friendly protocol amendments in clinical trials?

Protocol amendments can be complicated, and they require orchestration across multiple parties – sponsors, sites, and vendors – to ensure that the correct protocol information is being adhered to. In order to set all stakeholders up for success, it’s vital to be as clear as possible in every protocol amendment. This will result in reduced clinical trial site burden, fewer questions from technology vendors, and a decreased risk of protocol deviations.

To roll out your protocol amendments without disrupting your clinical trial workflows:

1. Track and outline specific changes when writing clinical trial protocol updates.
2. Maintain consistent numbering when updating I/E criteria.

(1) Track and outline specific changes when writing clinical trial protocol updates.

One of the most impactful steps you can take to reduce confusion with a protocol amendment is also one of the simplest. Provide a digital version of your protocol and include a clean, easy-to-follow outline of all changes to help sites and vendors quickly identify updates. 

• Provide a tracked-changes version of the protocol that highlights all text deletion, addition, and movement. When tracking changes, make sure to only highlight the updated text. Leaving messy strike-throughs and old text can lead to confusion.
• Outline all changes in a Summary of Changes section toward the top of the tracked-changes version for easy visibility. List all changes in order of the section they appear in, and don’t omit any changes – including those that may affect study design or subject eligibility (even if they aren’t necessarily the most major changes in the amendment). 

(2) Maintain consistent numbering when updating I/E criteria.

One of the common sections to undergo changes during protocol amendments is the section outlining the target subject population, which also typically includes the I/E criteria. Amendments provide an opportunity for sponsors to clarify, add, or remove I/E criteria to ensure that the right patient population is being enrolled, as well as to remove barriers to enrollment.

Often, amendments are driven by I/E criteria reporting. For example, sponsors who use StudyTeam have access to an I/E Criteria Report that visualizes patterns in I/E criteria failures. They can see overall percentages of failure across criteria, with an ability to filter those percentages by race and ethnicity, source, country, and more.

To minimize disruption to data reporting, consider the following examples, where one criterion needs to be added and one needs to be removed: 

• Don’t: Replace Criterion 1 with a brand-new Inclusion Criterion 1. By changing the nature of Criterion 1, data reporting would be affected because Inclusion Criterion 1 on Amendment A would be completely different from Inclusion Criterion 1 on Amendment B.
• Don’t: Remove Inclusion Criterion 1 and renumber the list of criteria, adding a new criterion to the end of the list. Even more data would be affected by the fact that Inclusion Criterion 3 on Amendment A would be the same as Inclusion Criterion 2 on Amendment B, and so on. 
• Do: Remove Inclusion Criterion 1 and change the text to “Removed in Amendment A,” maintain numbering for all other criteria, and add the new criterion to the end of the list. This method avoids renumbering and changing the nature of any criterion. It’s immediately clear that Criterion 1 is no longer relevant. Numbering is maintained for all unaffected criteria until the end of the criteria list, where there is an additional criterion on Amendment B that didn’t exist on Amendment A. This method results in minimal disruption to data reporting. 

Protocol amendments are necessary in clinical trials. So is clear protocol writing.

Being agile and amending protocols promotes patient safety, reduces barriers to enrollment, and improves overall trial quality. But making changes to any study protocol regardless of complexity involves a lot of moving parts, especially for research sites. Sites have to keep track of I/E numbering and text changes across protocol versions, and they have to do it for numerous studies and sponsor protocol formats. They also have to keep track of any changes to visit scheduling and activities, as well as other relevant information. 

StudyTeam for Sites tracks all of that information for sites and includes tools like the Visit Schedule, which calculates protocol-defined visit windows for sites automatically. The platform is built to manage all protocol versions, so sites can always work off the correct I/E criteria and visit schedule for the relevant protocol. This type of technology support keeps clinical trial workflows moving on time while reducing the risk of protocol deviations. 

Regardless of the technology you use to manage recruitment and enrollment, writing easy-to-understand clinical trial protocols and protocol amendments helps ensure enrollment and overall trial timelines stay on track. By providing as much clarity as possible when rolling out a protocol amendment, you set sites, vendors, and, ultimately, your trial, up for success. Sites have a better understanding of changes to protocol design and subject eligibility, which minimizes the risk of protocol deviation. Vendors like OneStudyTeam can easily implement amendments and provide better, cleaner data reporting to sites and sponsors.

Fewer questions, better data insights, and reduced protocol deviations mean that sponsors like you can focus their time and energy on what matters – developing therapies as quickly and effectively as possible.