How Does FDA's Single Trial Decision Change The Risk Calculus for Sponsors

In a conversation with Pharmaceutical Executive,Vera Pomerantseva, Director of Product Management for RBQM, eClinical Solutions, discusses the FDA's shift to a single pivotal trial for drug approvals. Pomerantseva explains that this change aims to provide stronger evidence of efficacy and patient safety, emphasizing the importance of risk-based approaches and AI in trial design and monitoring. She highlights eClinical's platform capabilities, including customizable centralized monitoring strategies and robust oversight across trial portfolios, to enhance efficiency and ensure regulatory compliance.

A transcript of Pomerantseva’s conversation with Pharmaceutical Executive can be found below.

Pharmaceutical Executive: How does FDA's decision to make a single pivotal trial the default fundamentally change the risk calculus for sponsors?

Vera Pomerantseva: I know there were some concerns that FDA lowers a scientific bar with the change, but they're not changing it. They're shifting where it sits. So I think we should be looking at the big picture of what does it mean for the industry.

So basically, FDA is saying that instead of proving it twice, we have to make it once, but make the evidence bulletproof. This is not a completely new process, to be honest. EMA already was doing it historically for a number of the trials. It also was practicing in the U.S. region, especially for the rare disease, and the goal is to provide strong evidence of efficacy and patient safety, as patient safety is always the highest priority and make sure that data integrity which are going to be provided as a output would reduce uncertainty and minimize biases of the trial.

So what it means is there are alternatives to having one trial instead of two. Again, we're focusing on the patient protection and strengthening the evidence of the scientific efficacy. So alternatively, it can be one larger, multi-center trial. It might be trial with very, extremely persuasive results, and we can strengthen it with the confirmatory evidence.

Again, we’re still figuring out the use cases, it might be the perfect one. There is so much data available to us, we just have to figure out how to use it, and this might be the perfect case.

The other thing which may strengthen the outcome is multiple independent cohorts within the standard to prove that the results are scientifically valid, and again, ensure patient safety. It's the number one priority for us. What it means is, depending on what approach we're going to take, we can translate it into the risks.

Again, the risk based approach becomes even more important with this shift, it is more important to think it through during protocol development, quality by design concept, what are the new risks and what you can eliminate or reduce during the design of the protocol before it becomes final?

Then, as you start executing the trial, right? What are the newer risks? Is it the complexity? Is it involvement and retention? So your centralized monitoring becomes a little bit more strategic with this change.