The biomedical research system has historically been supported by two main pillars: fundamental research on the mechanisms of disease, largely funded by the National Institutes of Health (NIH), and the pharmaceutical industry, which creates products to treat these conditions. Recent advances in biomedical research and health sciences present an opportunity to change how we understand, prevent, and treat diseases including infectious diseases, Alzheimer’s, and cancer.
A major initiative of the Biden Administration, the Advanced Research Projects Agency for Health (ARPA-H) was established in the fiscal year (FY) 2022 appropriations process to fill this opportunity gap. This new agency provides a mechanism for the federal government to support transformative high-risk, high-reward research to rapidly drive biomedical and health breakthroughs that cannot readily be accomplished through traditional pathways.
President Biden called for the creation of the Advanced Research Projects Agency for Health (ARPA-H) on lines of DARPA. “Folks, diseases like Alzheimer’s, diabetes, cancer — they’re all on the cusp of being able to be dealt with,” Biden said in a speech in May 2021 where he touted the ARPA-H. “You know, if we don’t do something about Alzheimer’s in America, every single, solitary hospital bed that exists in America — as the nurses can tell you — every single one will be occupied in the next 15 years with an Alzheimer’s patient — every one — costing us in excess of a trillion dollars.”
Health and Human Services Secretary Xavier Becerra announced in May 2022 the formal establishment of the Advanced Research Project Agency for Health (ARPA-H) as an independent entity within the National Institutes of Health and the appointment of Adam H. Russell, D.Phil., as acting deputy director. Currently, Dr. Russell is the Chief Scientist at University of Maryland’s Applied Research Laboratory for Intelligence and Security (ARLIS). And the agency now has it’s first leader, as President Joe Biden announced Renee Wegrzyn as director of the Advanced Research Projects Agency for Health, or ARPA-H, on Sept. 12, 2022.
Biden wants ARPA-H to replicate the success of DARPA, but in the health care realm, by providing “leadership for high-risk, high-reward biomedical and health research to speed application and implementation of health breakthroughs equitably.”
The idea is inspired by the Defense Advanced Research Projects Agency (DARPA), which follows a flexible and nimble strategy, undeterred by the possibility of failure, and has driven breakthrough advances for the Department of Defense (DOD) for more than 60 years. Energy (ARPA-E). Stakeholders identify a number of “DARPA model” characteristics for ARPA-H, including a flat and nimble organizational structure, tenure-limited program managers with a high degree of autonomy to select and fund projects, and a milestone-based contract approach.
In contrast, NIH relies predominantly, on the scientific peer-review process to award most of its funding. Some evidence suggests that this investigator-driven and the consensus-based process is less likely to fund high-risk, high-reward projects. ARPA-H was explicitly set up as an independent agency within NIH, in theory allowing it to benefit from the NIH’s vast scientific and administrative expertise and resources while still being nimble and forward-thinking.
Novel approaches outside of the traditional peer-review process have been successful at funding medical research and development (R&D). Notably, DARPA invested in Moderna’s mRNA vaccine technology—reportedly at a time when it was viewed with skepticism. The Biomedical Advanced Research and Development Authority (BARDA) has supported medical countermeasure R&D through flexible, innovation-focused R&D awards—including for Coronavirus Disease 2019 (COVID-19) products.
In a commentary(link is external) published in Science, White House Office of Science and Technology Policy Director Eric S. Lander, Ph.D., National Institutes of Health Director Francis S. Collins, M.D., Ph.D., and other leaders describe a vision for a new science entity, the Advanced Research Projects Agency for Health (ARPA-H). Included in the President’s fiscal year 2022 budget with a requested funding level of $6.5 billion, ARPA-H would accelerate biomedical innovation and adoption of technologies and approaches to revolutionize healthcare and medicine.
Lander and Collins, et al. write that ARPA-H should embrace a culture and approach similar to that of the Defense Advanced Research Projects Agency (DARPA) to champion innovative ideas in health and medicine. Put forth as a distinct division within NIH, ARPA-H would focus on time-limited projects with goals, benchmarks, and accountability to revolutionize how we prevent, treat, or cure a range of diseases, including cancer, infectious diseases, Alzheimer’s disease, and others. Projects supported by ARPA-H would focus on solving practical problems that foster breakthroughs to serve patients equitably — at levels ranging from the molecular to the societal — and drive them to the point of adoption. The authors argue ARPA-H could act as a mechanism to remove barriers and bring bold ideas to fruition more quickly.
Progress in medicine and health in recent decades has been driven by two powerful forces: pathbreaking fundamental research and a vibrant commercial biotechnology sector. Fundamental research is typically performed in university, nonprofit, and government labs. In the United States, it is mostly funded by the federal government, largely through the NIH. By steadily pursuing important fundamental questions in biology and medicine, scientists have made great progress in discovering the molecular and cellular mechanisms underlying health and disease—often suggesting new ideas for clinical treatment.
Such fundamental research is what economists term public good, in that it produces knowledge available to everyone and thus requires public investment. Some have estimated that every dollar of federal investment yields at least $8 in economic growth, and suggested that every new therapeutic approved by the US Food and Drug Administration (FDA) can be traced, in part, to fundamental discoveries supported by NIH. Given its outsized impact, robust federal investment in fundamental research remains crucial to health and to the economy.
The commercial sector is largely focused on research, development, and marketing of specific products, to bring sophisticated therapies and devices to patients. Biotechnology companies have access to abundant capital to develop products—provided they can protect their intellectual property and recoup the costs by generating sufficient profit in a short enough period of time. Currently, more than 8000 medicines are in development, including 1300 for cancer.
Bold ideas may not fit existing mechanisms because (i) the risk is too high; (ii) the cost is too large; (iii) the time frame is too long; (iv) the focus is too applied for academia; (v) there is a need for complex coordination among multiple parties; (vi) the near-term market opportunity is too small to justify commercial investment, given the expected market size or challenges in adoption by the health care system; or (vii) the scope is so broad that no company can realize the full economic benefit, resulting in underinvestment relative to the potential impact.
Although DARPA is an excellent inspiration for ARPA-H, it is not a perfect model for biomedical and health research. It serves the needs of a single customer, the DOD, and its mission is focused on national security. Its projects typically involve engineered systems. By contrast, health breakthroughs (i) interact with biological systems that are much more complex and more poorly understood than engineered systems, requiring close coupling to a vast body of biomedical knowledge and experience; (ii) interact with a complex world of many customers and users—including patients, hospitals, physicians, biopharma companies, and payers; (iii) interact in complex ways with human behavior and social factors; and (iv) require navigating a complex regulatory landscape. ARPA-H can learn from DARPA, but will need to pioneer new approaches.
ARPA-H should have a clear mission. Building on DARPA’s mission statement, an initial mission could be: “To make pivotal investments in breakthrough technologies and broadly applicable platforms, capabilities, resources, and solutions that have the potential to transform important areas of medicine and health for the benefit of all patients and that cannot readily be accomplished through traditional research or commercial activity.”
NIH has some experience with running large, complex programs using DARPA-like approaches to drive highly managed, use-inspired, breakthrough research. A classic example was the Human Genome Project, aimed at reading out the complete 3 billion–nucleotide human genetic code. When the project began in 1990, the technology to accomplish the goal hadn’t been invented. By driving innovation, it was completed ahead of schedule and ultimately decreased the cost of sequencing a human genome from $3 billion at the outset to $500 today. Though estimates vary, it is clear that the overall economic return on investment has been enormous, with notable analyses estimating a nearly 180-fold return .
A very recent example is the NIH’s response to the COVID-19 pandemic. Within weeks, NIH created two programs. The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program is an unprecedented partnership with government, industry, nonprofits, and academia to drive preclinical and clinical therapeutics, developing master protocols for testing prioritized compounds in rigorous randomized clinical trials. These efforts accelerated the development and testing of several of the vaccines that are now being widely used. The Rapid Acceleration of Diagnostics (RADx) program used an “innovation funnel” approach to identify promising ideas for COVID-19 tests and support 32 new technology platforms that collectively are contributing 2 million tests per day, mostly at point of care.
Although these programs have been successful, they required bespoke solutions and herculean efforts to get them off the ground. Because NIH lacks a regular framework for such projects, many bold ideas are hard to realize. That’s where ARPA-H can help, write Lander and Collins, et al.
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