Selective Safety Data Collection and the Case for Simpler Trials: Q&A with Rob DiCicco, TransCelerate Biopharma

As the clinical trial industry searches for practical pathways to simplification, selective safety data collection has emerged as one of the more compelling models—grounded in regulatory collaboration, supported by real-world evidence, and potentially scalable in ways that previous pragmatic trial efforts have not been.

To explore this further, Applied Clinical Trials spoke with Rob DiCicco, vice president of portfolio management at TransCelerate Biopharma, about what the FDA and TransCelerate collaboration has produced, how reducing visits and assessments affects trial quality, and where selective safety data collection could take the broader enterprise of trial modernization.

ACT: What is most operationally significant about the FDA and TransCelerate exploring selective safety data collection in clinical trials?

DiCicco: The thing I'm most jazzed about is that we developed four separate scenarios—four different regulatory scenarios describing four different levels of maturity for medicines across four different therapy areas. If a sponsor organization were looking to de-risk one of their programs and wanted to take this approach, there's a pretty good chance that within the assets we've created with FDA and the public summary we've released—we do intend to publish all of those use cases—you can find something that fits with your own portfolio and move it forward. It gives you a blueprint of what it could look like and helps you de-risk the ability to go forward with confidence.

It also gives you a sense of how to engage the agency and make sure you have the right representation across teams. One of the things we've heard from sponsors is a concern that not everybody across FDA might be on the same page with respect to supporting one approach or design over another. Working with CTTI is a means to actually bring the right expertise across policy, review divisions, OSI, and others as needed, to give yourself the assurance that you're moving forward with a plan that will work.

ACT: How could risk-based safety data collection reduce burden on sites and patients without compromising trial quality?

DiCicco: I was hoping you'd ask that. If you refer to the FDA white paper published by CTTI last summer, it explores three different ongoing or recently completed programs that employed selective safety data collection. The document lays out tables comparing what was done in the randomized controlled trial portion of the registration program to what was done using selective safety data collection, and you can see the number of visits and assessments going down somewhere in the neighborhood of 50 to 75% across those three trials.

In terms of quality, you have to think about the greater context, which is the use of pragmatic elements in clinical trials. Selective safety data collection almost defines a portfolio of studies for medicines that are fairly mature and have a lot of robust safety data behind them—that's where some of the assurance on quality comes from. The agency also did some analysis in the late 2010s on studies that could have employed selective safety data collection but didn't, comparing what the output would have looked like if they had collected less. The answer was that it wouldn't have changed the assessment or uncovered new issues.

And remember, it's selective safety data collection, not zero safety data collection. We're still going to collect AEs of interest, AEs that require participants to withdraw, and serious adverse experiences.

ACT: What impact could this approach have on decentralized or more real-world-oriented trial designs?

DiCicco: I think what it does is take enough risk out of a pragmatic trials program to make it scalable. The term "pragmatic trials" has been around since the late 1960s, and if you looked at ten of them, you'd see ten individual examples. Ask ten different people or ten different consortia what they're working on, and you'd get ten different answers. It's hard to come up with common currency. But if you think about the pragmatic elements that actually make a difference—expanded inclusion/exclusion criteria, reduction in the number of visits and assessments—and the same thing with selective safety data collection, you get to a place where you can reduce risk in a way that becomes scalable.

Any sponsor could do a pragmatic trial once, or a decentralized trial once. But trying to scale these things and do them all the same way, with the level of workarounds involved in figuring it out for the first time, is a big difference from moving from a pilot or one-time effort to actual scale. That's where the real difference is—being able to scale these approaches, and that's where you see a real net reduction in effort, burden, and cost.

ACT: How important is growing alignment between regulators and sponsors when it comes to modernizing trial execution practices?

DiCicco: The pharma industry has been described as massively risk averse, and there's a reason for that—patient safety is tantamount, and the investment is significant. Nobody wants to get to the end and find out there was an issue that could have been solved for. The platform that CTTI has created, with their step program and educational materials like their white paper on SSDC, is meant to help de-risk and ratchet down perceived risk. The tabletop exercises we've engaged in with CTTI and CDER have led to a lot of myth busting, some of which comes out in the public summary we produced.

The agency has also expressed a keen interest in understanding where our pain points are. Sharing the realities of things that aren't doable at scale in a certain environment—like point-of-care trials, if we really want to scale those up and make trials more accessible to different healthcare communities and sites—is very important.

And it's not just regulators and sponsors. There needs to be a partnership between regulators, sponsors, healthcare practitioners, and patient communities as well. The recently published update to ICH E6, the R3 update, talks a lot about quality by design and stakeholder engagement in study planning and design. That's where the real opportunity is—getting input not only from agencies and sponsors, but from investigators and patients too.

ACT: Looking ahead, could selective safety data collection become a broader model for simplifying clinical trial operations and oversight?

DiCicco: I think there is an incredible amount to learn here. It begins the practice of simplification. All types of programs—pragmatic trials, DCTs—get much easier when you simplify. That's part of the challenge of doing these things at scale, so it builds that muscle. I think it drives innovation in how we think about assessing data quality and sponsor oversight, especially when you want to expand the pool of available investigators. We have a relative deficit relative to demand, especially in the US, and we're losing investigators from the pool over time. So it becomes critical to make these trials more doable.

I think finding that niche where the friction is low and the risk is low—because you're talking about programs where the assets are fairly mature, where there's a good solid foundation of safety and efficacy data behind them—is a fabulous opportunity to not only expand access for clinical trials but to learn how to take that approach and figure out where you can rinse and repeat it into other parts of the clinical trials enterprise.