Q&A on Implications for FDA under ARPA-H
Implications for FDA under ARPA-H
Caveat: The Alliance for a Stronger FDA is neutral on ARPA-H (it is outside our mission), but if ARPA-H does come into existence, we want to be sure the FDA has the resources to be a full partner.
Q: What is the DARPA model and why would the President and some Members of Congress want to replicate it in the biomedical space?
A: DARPA tackles large difficult problems with the goal of quick, break-through advances that benefit our national defense. It is biased toward challenges that require unconventional thinking and a “Manhattan Project” approach. There is a widespread perception that the DARPA approach can take on challenging problems in a manner that would be difficult to achieve in the more deliberative and more iterative NIH approach. There is a benefit to having both models—indeed, Congress is in the process of giving NIH a funding bump while considering creation of ARPA-H.
Q: What will ARPA-H look like and how will it emulate DARPA?
A: There are many differences between defense research and biomedical research, so there are a substantial number of questions that House E&C and Senate HELP will need to address.
The perceived similarity: ARPA-H is intended to rapidly accelerate solutions for the toughest disease challenges and do so in record time. The intention is to normalize projects like “stimulate development and reach approval for a COVID-19 vaccine and do it in a fraction of the time it would ordinarily take to develop and approve a vaccine.” As envisioned, ARPA-H will want to be working on several of these advanced transformational projects every year.
Q: What role is FDA likely to have if ARPA-H is created and how would it be different than what FDA already does every day?
A: ARPA-H projects are intended to be ground-breaking (“bust the paradigm/break down the barriers”) and will require early, time-consuming, and intensive FDA involvement. FDA will need to be there at the beginning of each project, working out metrics for safety and efficacy and clinical trial design and then work with product developers at every stage thereafter. The ARPA-H that is being envisioned will demand a far greater level of FDA involvement than any supposedly-similar funding initiative.
Q: Will ARPA-H work require far more agency involvement than the normal mix of products the agency reviews?
A: Ground-breaking products, such as gene therapies, are always more resource-intensive than more traditional therapeutic approaches. In particular, good trial design, endpoints, clinical pathways and metrics of safety and efficacy are difficult to develop in areas where:
the natural history of the disease is not well understood, or
disease manifestations and progression are heterogenous across patients, or
measurement is difficult, or
years of data will be required
In these types of situations, FDA has often invested hundreds, and occasionally thousands of hours, before a product has reached the NDA/BLA/PMA stage.
Q: Won’t user fees paid on the final products compensate FDA for the large investment in ARPA-H projects?
A: User fees never pay for the full cost of FDA’s work on medical product development. Budget authority (BA) appropriations pay for about 30% of the cost of drug reviews and a much greater percentage for medical devices and most other medical products. If ARPA-H is created, FDA’s responsibilities will draw resources from FDA’s BA appropriations even if user fees are eventually collected.
Also, because ARPA-H projects are intended to be ground-breaking, the number and percent of failures is expected to be high. If FDA is to be “compensated” for its time on ARPA-H projects, some of the most time-consuming work will be staffed entirely from FDA’s BA funding.
Editorial Note: The Analysis and Commentary section is written by Steven Grossman, Executive Director of the Alliance for a Stronger FDA.