Operation Trial Blazer

This week, the US Department of Health and Human Services (HHS) announced a new initiative called ‘Operation Trial1 Blazer’ that aims to bring back early-stage clinical research, which has increasingly been outsourced to countries like China and Australia, by reducing how long it takes to get approval to start phase 1 trials as well as how long it takes the FDA to review data from phase 1 trials.

The initiative includes several parts. One is an FDA pilot program to set up a network of qualified research institutions that help researchers prepare the protocol and supporting components before they submit it, though the FDA still decides whether a trial can proceed. It also provides more guidance on what manufacturing (CMC) data is needed for phase 1 and clarifies this is lower than for later-stage trials – companies have so far tended to submit more data than necessary to secure approval. And it includes guidance on choosing the first doses given to humans, recommending these are based on statistical modelling of the drug’s pharmacology rather than animal toxicology studies, which were often poor predictors of side effects in humans. Finally, there’s a rolling platform for the FDA to review components of the package as they arrive rather than all at the end.

Most of this sounds positive, though I’d add a caveat of the main bottleneck facing the FDA right now: staffing capacity, given the cuts over the last few years (roughly a fifth of the agency’s workforce, around 3,500 FDA staff, were cut last year), and whether these reforms ease that problem or worsen it further. Rolling reviews especially require more staffing time, because reviewing at the end typically means some attrition from researchers who don’t make it to that stage; similarly, if the FDA still has to make the final decision on whether phase 1 trials can proceed, especially given this initiative is new and will take their input. Still, there’s good stuff here: the guidance on manufacturing data and dose selection doesn’t depend on FDA capacity the way the pilot does, so some of these changes could result in improvements soon.

For more thoughts on the new policy, Ruxandra Teslo and Adam Kroetsch also weighed in.