The HHS (FDA, NIH, ARPA-H and related agencies) is moving to speed clinical trials in what they are calling Operation TrialBlazer (kudos on the pun). The motivator, of course, is China:

China has made biotechnology a strategic national priority, systematically expanding its clinical research infrastructure with government backing, streamlined regulatory pathways, and sustained investment. In 2021, China’s global share of Phase 1 trials surpassed the United States’ share for the first time, a milestone that would have seemed unlikely just a decade earlier. And in 2024, China surpassed the United States in the total number of clinical trials registered, with over 7,100 registered, representing 39% of global trials…. For certain cutting edge modalities, including cell and gene therapy, radioligand therapy, and stem cell therapy, China uses investigator-initiated trials to provide additional flexibility, though with some tradeoffs around oversight and quality control. This means that drugs can move into human testing if a researcher has an interest and funding. In the U.S., comparable trials might wait years to start.

I am also pleased to see that they mention Australia, another advanced democracy, as a leader in clinical trial regulation:

Australia’s Clinical Trial Notification System allows trials to begin in fewer than 70 days after a final protocol is submitted, with regulatory approval granted in as little as 21 to 28 days and sites activated within 6 to 12 weeks.

Keep those comparisons in mind. Operation TrialBlazer proposes some good reforms such as CMC clarification. CMC is Chemistry, Manufacturing, and Controls–and it deals with the basics of manufacturing a drug. The FDA, however, is very risk averse and companies know that so they have often gone overboard in CMC: for example, proving stability of a formula at 6+ months when the trial is to last only a few weeks or documenting their full commercial manufacturing process before they even know if the drug works and knowing full-well that the process will be changed many times before a drug actually gets to market. In short, a lot of cost for very little benefit. The FDA is now clarifying that this kind of thing is not necessary. Good, that is low-hanging fruit. There are other good ideas as well.

But note what they are not proposing. Despite using China and Australia as exemplars they are not going down either path. Where China is fastest is in cell therapy, gene therapy, radioligand, and stem cell work and in these areas, China lets trials proceed on an investigator-initiated basis: as the TrialBlazer document puts it, a drug can move into humans “if a researcher has an interest and funding.” China then combines this open (or lax) front end (for these products) with an all-of-government industrial policy to accelerate winners.

The US is declining to go down that path. Ok, not my call, but I get it. But they are also declining to follow Australia. In Australia there is also no government prospective regulatory evaluation of most early-phase clinical trials. Under the Clinical Trial Notification (CTN) scheme, the sponsor submits their protocol package to a Human Research Ethics Committee (HRECs)–Australia’s IRBs–and once the ethics committee approves, the sponsor notifies the regulator, the Therapeutic Goods Administration (TGA), and pays a fee. The TGA does not read and clear the package before the trial starts. The roughly 21-to-28-day “approval” and sub-70-day start figures in the document are fast precisely because the regulatory step is not an evaluation. The government regulator stays out of the front end for most clinical trials, although in direct contrast with China it does step in for the highest risk biologicals. China has decided, high-risk, high-reward.

Australia does certify the certifiers, the HRECs. Europe uses a similar system for medical device approval. It’s a system proposed by former medical officer at the FDA Henry Miller and one I have long supported for the US. China is more laissez-faire.

The US architecture in contrast rests on the “gold standard” FDA reviews and the “FDA will retain full regulatory authority and decision-making.” In short, all of the TrialBlazer reforms are about making the gatekeeper faster, cheaper to prepare for, and less uncertain. None of it is about getting rid of the gatekeeper.

Addendum: Full disclosure, I did some consulting with ARPA-H on related work. See also my previous post on the a radical deregulatory approach, Montana’s SB535 and a Potential Biotech Renaissance in America