Strategies for Embedding Protocol Flexibility

In a recent video interview with Applied Clinical Trials, Vera Pomerantseva, director of product management, RBQM, eClinical Solutions, discussed FDA's recent guidance on protocol deviations and its impact on clinical trial management. She highlighted the importance of quality by design (QbD) and critical to quality (CTQ) factors in reducing protocol deviations. Pomerantseva views this guidance as an official acknowledgment of existing practices and an opportunity for improvement.

ACT: What are some strategies that stakeholders can use for embedding protocol flexibility during risk assessments?

Pomerantseva: The strategy to embed flexibility, I think, should be an essential part of protocol design and risk assessment. This is the one of the key QBD activities, so a cross-functional team must be involved and an environment which fosters open dialogue should be created. We call it quality culture. Again, I know it's easier to say than to create it, and by the way, in 2022, MHRA issued a guidance clarifying lots of questions about the protocol risk assessment and monitoring oversight and I think they did an excellent job outlining the roles to be involved in the protocol risk assessment and basically how it should be done. The protocol should be reviewed by this cross-functional team to assess it from the different angles looking at the complexity, the burdens, unjustified restrictions, and maybe as an example, here are some questions which can be discussed by this team during their meetings, so what requirements can be less restrictive? Is everything that is in the protocol scientifically justified. Do we really need all these assessments in this protocol, and if we need them, do we need them in this particular format and with that particular frequency? How flexible should your visit windows be? Again, if you decided it's going to be plus/minus days without the need, you just created a problem for yourself, you're going to have a lot of protocol deviations. Do they really impact anything? Maybe not. It's, again, quality by design thinking.