By Deborah Borfitz

July 8, 2019 | Growing numbers of study sponsors have been adopting the Common Protocol Template (CPT)—or at least its basic structure—since TransCelerate BioPharma released the first version in 2015. The CPT is a harmonized, streamlined approach to formatting and adding content to clinical trial protocols, and is intended for use across therapeutic areas and phases, according to Virginia Nido, global head, product development industry collaboration at Genentech, a member of the Roche group.

The rationale is to ease interpretation by study sites and global regulatory authorities while enabling downstream automation of many clinical trial processes and aligning to industry standards, explains Nido, who serves on TransCelerate leadership committees. The CPT includes a common structure, proposed model text, and regulator-accepted endpoint definitions that may be used across protocols with little to no editing.

The CPT work group is hopeful the template can fit all design options, Nido says. That includes, ultimately, master protocols involving the addition or removal of drugs, arms and hypotheses from an ongoing trial. TransCelerate is actively looking at what updates would be needed to accommodate such novel study designs, which are expected to gain ground over the next several years.

Guiding Principles

The CPT is updated annually—the current version is the sixth iteration of the document—and in parallel with the Food and Drug Administration and National Institutes of Health, which have developed their own common protocol template for investigator-initiated studies, Nido says. The protocol templates are "90% the same... our [respective] tables of contents look almost identical as do many sections of text."

Guiding principles of CPT development were to ensure information in a study protocol is always in the same place and means the same thing, says Nido. The goal was a streamlined human-readable template where endpoint definitions align with CDISC standards. The CPT was also developed so that content is machine-readable and can automatically populate downstream documents such as clinical study reports and statistical analysis plans.

"We want investigators in particular to be able to quickly find scientific information and the schedule of events… to see if it is feasible for their site to do a study and if they have the patient population to complete it," says Nido. If sites are no longer poring over lengthy, complicated protocols because the information they need most is up front and the information they need least is in appendices, "they will have more time to spend where it is needed most—with patients."

With the technology-enabled edition of the current CPT, large sections of text from the protocol can be treated as variables with the touch of a button, continues Nido, reducing a lot of error-prone data reentry when recreating the downstream documents. The CPT includes participant libraries to assist protocol writers and editors with language specific to patient groups, such as pediatrics and healthy volunteers.

Regulators and ethics committees can similarly benefit from the ease of finding information in a CPT, she adds.

Adoption Challenges

Last year, the participant library expanded to include devices and vaccine trials, says Nido. The CPT also became better aligned with ICH good clinical practice guidelines. Within the next two years, ICH is expected to issue a guideline, template and technical specification for a common electronic structured protocol, built in part on the foundations of TransCelerate's CPT.

The hard part is convincing individual biopharmaceutical companies to make the switch because pride of ownership around existing protocol language tends to blind people to its potential flaws, says Nido. The tendency has been for companies using TransCelerate's CPT to "over-customize" it, although those that did are "walking that back" after realizing it had repercussions for content reuse.

"We need to be rather ruthless and ask ourselves if [what we have] is truly better or can we live with language selected by 19 of our peer companies," Nido says. "The boilerplate language is common across all protocol needs and therefore doesn't need to be customized by individual companies. It's sufficient to give investigators what they need to guide patients. I want our science to shine through and the potential therapy to capture investigators' interest. We don't need to be competing on our protocol template."

Use of the CPT is optional for TransCelerate member companies. "We are trying, however, to get companies that are using the CPT to adopt at a minimum the level one and two headings," says Nido. "If you're not doing that it's hard to say you're using it." Level three headings "have always been flexible," she adds, but sponsors have been asked to mark any unused ones with "N/A" in lieu of renumbering to help maintain template consistency.

The CPT is publicly available and most TransCelerate member companies are in various stages of adopting the template, says Nido. "We have not yet reached a tipping point in the industry where the majority of protocols are [CPT-based]... but I hope we will be there soon."

"Hopefully protocols are becoming more streamlined and readable so sites and regulators can find information easily and more consistently across sponsors," Nido says. There has been discussion about possibly having companies voluntarily put an identifying stamp on TransCelerate-derived protocols and asking sites for feedback on the CPT during investigator meetings, she adds.