Balancing Speed and Rigor in Accelerated Trial Pathways

In a recent video interview with Applied Clinical Trials, Meri Beckwith, Co-CEO, Lindus Health, discussed the evolving perception of breakthrough designation amid the FDA’s recent Complete Response Letters (CRLs) issued to Replimune and Capricor. He emphasized that breakthrough designation does not necessarily guarantee approval, but offers quicker decision access and investor signaling. Beckwith also stressed the importance of agility in trial design, advocating for adaptive trials and control groups where ethical. To mitigate regulatory unpredictability and avoid costly CRLs, he highlighted the need for future-proofing trial protocols with adaptive randomization and synthetic control groups.

ACT: How should clinops leaders balance trial design for accelerated pathways like breakthrough or priority review, while still meeting the FDA’s rising bar for adequate and well-controlled studies?

Beckwith: I'd go back and say just because you have a breakthrough designation doesn't mean you should treat the trial design process, or approach the trial with any less rigor. I think most people are on board with that. I think that the best thing that sponsors can do in these times of uncertainty with the FDA is to cultivate agility. If the worst happens, and the FDA effectively moves the goal posts on you, and you need to generate more data, cultivate agility in your organization to be able to generate that data or even an entire new study, worst case at a reasonable cost. I think the way I've observed a lot of the industry operates is it's in a very kind of waterfall fashion, where you specify a study design, you agree on it with the FDA, you gold plate it by trying to throw every conceivable mitigation at it, and that makes these studies lengthy and expensive. This is things like 100% SDV, extra-long follow up periods, many, many secondary and exploratory endpoints, and so on. What I think some sponsors could be better served by, is cultivating the agility necessary to be confident in a study design, but then be ready to generate additional data, and do that quickly if need be without this very laborious gold plating process. Ultimately, it's about more shots on goal. I think that's the best way to insulate yourself against the uncertainty.