Evolving FDA Risk Tolerance Reshapes Global Trial Alignment

In a recent video interview with Applied Clinical Trials, Charlie Paterson, partner at PA Consulting, discussed how reduced FDA capacity and significant staff turnover in 2025 have reshaped regulatory engagement and operational planning for clinical trials. Paterson explained that sponsors are facing longer timelines for meetings and decisions, prompting greater upfront investment in submissions and more conservative planning. He also outlined how slower FDA guidance is influencing trial design choices, limiting adoption of innovative approaches, and driving sponsors to rely on precedent and non-US regulatory frameworks. The conversation explored where regulatory uncertainty is most acute across the development lifecycle and how evolving risk tolerance at the FDA could further globalize clinical trial strategies.

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

ACT: How do you see the FDA’s current approach to risk affecting the speed and design of clinical trials, and what challenges does that pose for sponsors in practice?

Paterson: It depends on how you interpret current risk tolerance. At a leadership level, the narrative suggests a higher tolerance—expedited timelines, voucher schemes, single pivotal trials, and AI adoption all point in that direction.

However, internally, we see increasing risk aversion due to loss of institutional expertise. Guidance on new approaches isn’t forthcoming because divisions may not have the depth of experts needed to engage deeply with innovators. That can lead to more conservative guidance and more clinical holds.

This creates a double-edged sword. Publicly, the FDA appears bullish on speed and innovation, but turnover has slowed things down in practice. Globally, that pushes organizations to look to the EMA, MHRA, PMDA, and Health Canada for guidance.

Clinical programs are becoming more global, with certain geographies accelerating their ability to host studies—sometimes hosting activity that previously would have launched first in the US.