Clinical trial plain language processes can mean authoring with the end in mind

The route to developing operational processes and efficiencies between plain language protocol synopses (PLPS) and plain language study summaries (PLSS) – or what is pre-trial information vs. post-trial information for public consumption – varies within sponsor companies, as much as it varies on the best practices that are still evolving.

“Overcoming Operational Challenges with Plain Language Summaries” panel.

At the Clinical Data Disclosure Europe conference this past November, moderator Jaclyn Spedaliere, senior director, Commercial Strategy & Delivery for Citeline, walked sponsor panelists Joe Carroll, senior manager, Clinical Transparency and Trial Disclosure for Regeneron and Emily Regan, senior manager, Disclosures, Global Regulatory Affairs at Sarepta Therapeutics, through the issues of “Overcoming Operational Challenges with Plain Language Summaries.”

Spedaliere prompted the sponsor panel to describe how they developed a process creating their documents and how they identified which studies would need a plain language summary and the choice depended on whether it was a PLPS or PLSS. Regan said, “For plain language protocol synopsis, we only do these if it's required by CTIS and the EUCTR. However, for plain language trial summaries, or study summaries, we're going to be creating those for all studies going forward…whether or not they are required by EUCTR.”

Similarly, Carroll noted that Regeneron will be providing language summaries for any of the studies that would have “public facing results moving forward from this year.” That would include CTIS, or studies with a local country requirement, such as UK MHRA or Turkey, as well as if the results will be on ClinicalTrials.gov.

With regulations driving the identification of the studies that will have plain language summaries, the remainder of the discussion focused around operational issues, such as timelines; relationship to PLPS, and an few challenges.

Timelines

At Sarepta, Regan noted that most of their current studies are in pediatric populations, which require a six-month timeline with CTIS. She explained the way they work is as soon as they have a draft for the technical results, the team reviews that. And almost in parallel, they will review the plain language summary. “It’s an intensive few weeks getting everything done, but we're trying to keep them in parallel as much as possible,” said Regan. The benefit of running them in parallel according to Regan is comparing them so that the technical results in the plain language summary are matching up.

In addition to this parallel timeline, the Regeneron team has the Clinical Study Report (CSR) in development, so they compare the draft CSR summary for consistency. “It's quite a sprint for those last few months to hit that six-month mark,” said Regan, but she alluded to the benefits of including the same language into the PLPS, PLSS and CSR templates, making for robust templates. “Hopefully, a lot of it is plug and play once the data is ready.”

Regeneron works with a vendor, which Carroll noted, helps drive their timelines with the PLPS (two to three months) and the basic six-month PLSS. Carroll said, “There were a few that we had to push through a little quicker than that. But, as long as we make everybody aware of the urgency, and keep the process moving, it goes along well.” In addition to processes, Carroll said that the same people are included on both the PLPS and PLSS review process, which helps. Specifically, Carroll said, “During the technical summary results, for example, we might have discussion about how certain endpoints would be approached. Once we've had that conversation, we can communicate during the review that the conversation was had and approved, which helps.”

Challenges

Language: Authoring documents more easily by doing more upfront—or authoring with disclosure in mind—took the Sarepta example of parallel process into some challenges. For example, outcome measure descriptions. While the PLPS includes some of what will be covered in the PLSS, Regan described the challenge of how to capture and translate a scientific measure into lay language. “I've been on calls where we're talking about one word for 30 minutes, so it's quite a hot topic and people get passionate about it, which is excellent, but once you iron that out with the PLPS, then plugging that in for the results summary, makes it a lot easier,” said Regan.

According to Spedaliere, some sponsors use glossaries, others libraries of terminology, to achieve consistency. Early on, Regan said they stuck very hard to the glossary definitions, but have now switched to “a living breathing glossary” that has improved the language using team suggestions.

Secondary Endpoints: Many sessions at the conference discussed the inclusion of secondary endpoint outcomes in the PLSS. From Carroll’s perspective, when a study team really wants to include secondary endpoints, it helps to remind them what the goal of the PLSS is. “The main focus should be the primary endpoints. And if we start to do secondary endpoints for this study, we're going to need to do it for all the other studies, explained Carroll. “And not only do we not want to do that for the reason it's going to make the report too long. We can’t cherry pick the secondary endpoints. we want to make sure that we're treating all the PLSS the same.”

Regan agreed. “If we start including them, then does it not become a lay summary anymore? It's not understandable. It's too long. And then also picking them, because there can be anywhere from 10 to, you said, 100 secondary endpoints.”

That comes down to an issue of impartiality, basically, as the audience discussed the importance of not just choosing the “good” ones but providing an accurate description of the study and its results. Remember, the PLPS must include primary and secondary endpoints, and the PLSS only requires primary endpoints and safety information.

This robust discussion also included the use of vendors to ensure neutrality, the use of patient panel reviews for additional confirmation of the use of language and what information is important to a patient, as well as distribution of PLSS after the study. To learn more about these topic discussions, please visit our upcoming conference Clinical Data Disclosure, Transparency and Plain Language Summaries.

Quotes have been lightly edited for clarity.

Depositphotos@Chris2766