Mike's Blog

Over the past several years, there has been increasing recognition that the United States is losing ground to other nations – particularly China and Australia – as the preferred location for pharmaceutical and biotech companies to conduct clinical research activities. Primarily as a result of regulatory innovation in those countries, companies have found that investigational new drug (IND) applications have been streamlined to achieve first-in-human clinical trials much faster. In addition, these countries have enabled rapid initiation and implementation for subsequent clinical trials. As a result, there is growing concern that longer times and processes for U.S.-based drug approvals and development will delay the introduction of new and improved treatments and erode the perception of the US as the global leader in biomedical innovation. This issue and related competitiveness reforms was one of the former FDA Commissioner priorities with Karim Mikhail (now the acting head of CBER and our keynote speaker for the Annual CTSA Fall meeting) taking the lead in addressing.

This undertaking has now been elevated to an HHS priority with the snappy moniker of ‘Operation Trialblazer’ (with the attendant spellcheck and autocorrect result) and has engaged other HHS agencies in addition to FDA, including CMS, ONC, ARPA-H, and of course, NIH. On June 22, HHS publicly announced this effort. In attendance with the NIH Director were directors from NCI and NCATS, each of whom provided remarks. Several non-USG individuals from across the health care spectrum also provided comments including Emma Meagher from University of Pennsylvania who provided some nice shouts-outs to the CTSA Program as well as N3C.

So exactly what is Operation Trialblazer? Follow-up media reports from the HHS announcement focused nearly exclusively on the FDA component and mainly on the streamlining of the IND process. This is a major element of the overall activities, but there is more, in particular, a focus on increasing the efficiency of clinical trials. All of the activities will likely involve CTSAs.

INDs are a major sore point for the FDA. China and Australia have introduced innovative reforms to their processes that greatly shorten early clinical development timelines. The FDA is interested in similar types of innovations. One aspect under discussion is the number of annual IND submissions (~5000) of which nearly two-thirds are actually research INDs and are unlikely to result in either an BLA, NDA, or sNDA. Many are academic research studies using approved drugs to answer a mechanistic question. Another example (as highlighted by a CTSA PI) is the use of a dietary supplement when the IRB asks for FDA review. FDA is considering offloading these types of INDs to ‘qualified’ regulatory centers (think academic medical centers) that have particular type of expertise such as vaccines or drug development.

Beyond INDs, there is a focus on overall clinical trial efficiency. NCATS has already initiated discussions with Building 1 at NIH regarding IRB reform and the implementation of standardized clinical site contracting. Utilization of AI is in the mix, including recruitment tools.

You can expect that many of the ‘innovations’ and ‘reforms’ that will be considered are endeavors that many of you want to see happen anyway. I know CTSAs and TIN have been actively working in this space for quite a while. The difference now is that this has suddenly become a priority for HHS and will have NIH endorsing and promoting these actions.

Buckle up!

We are embedded in habit. We dread the truly new, the truly emergent. We don’t fear the end of the world—we fear the end of the world as we know it.
- Ray Nayler, The Mountain in the Sea