tl;dr

Some breakthrough ideas don’t receive sufficient attention because they are too high-risk, high-cost, or long-term, because they don’t fit well into academia or the commercial sector, or because they require complex collaborations. ARPA-H aims to support promising opportunities which concern health but which fall in that gap. ARPA-H will not have intramural labs. It will facilitate research directed at solving practical problems. To date, the kinds of non-dilutive funding opportunities which will be available through ARPA-H (grants, contracts, etc.) have not been defined, but they may be similar to those of DARPA.

The Back Story

In March 2022, Congress passed a spending bill which provides $45 billion for the NIH, an increase of $2.25 billion over last year. That sum includes $1 billion to establish the Advanced Research Projects Agency for Health (ARPA-H). (Read more here.)

What is ARPA-H?

In his 2022 State of the Union address, President Biden envisioned ARPA-H as the DARPA for health:

I call on Congress to fund ARPA-H, the Advanced Research Projects Agency for Health. It’s based on DARPA—the Defense Department project that led to the Internet, GPS, and so much more. ARPA-H will have a singular purpose—to drive breakthroughs in cancer, Alzheimer’s, diabetes, and more.

Congress heeded President Biden’s call and appropriated $1B for the new agency

Here’s the legalese:

For carrying out section 301 and title IV of the PHS 19 Act with respect to advanced research projects for health, $1,000,000,000, to remain available through September 21 30, 2024:

Provided, That the President shall appoint in the Department of Health and Human Services a director of advanced research projects for health (Director):

Provided further, That funds may be used to make or rescind appointments of scientific, medical, and professional personnel without regard to any provision in title 5 governing appointments under the civil service laws:

Provided further, That funds may be used to fix the compensation of such personnel at a rate to be determined by the Director, up to the amount of annual compensation (excluding expenses) specified in section 102 of title 3, United States 7 Code:

Provided further, That the Director may use funds made available under this heading to make awards in the form of grants, contracts, cooperative agreements, and cash prizes, and enter into other transactions (as defined in section 319L(a)(3) of the PHS Act):

Provided further, That activities supported with funds provided under this heading shall not be subject to the requirements of sections 406(a)(3)(A)(ii) or 492 of the PHS Act:

Provided further, That the Secretary may transfer the Advanced Research Projects Agency for Health, including the functions, personnel, missions, activities, authorities, and funds, within 30 days of enactment of this Act to any agency or office of the Department of Health and Human Services, including the National Institutes of Health:

Provided further, That the Committees on Appropriations of the House of Representatives and the Senate shall be notified at least 15 days in advance of any transfer pursuant to the preceding proviso.

Note the ambiguity about whether ARPA-H will be part of NIH. It is part of the Department of Health and Human Services (HHS). It may or may not be a part of the National Institutes of Health (NIH), which is also part of HHS. Whether ARPA-H will be part of NIH or an independent agency in HHS remains an open question–and a controversial one. Last year, some argued that nesting ARPA-H under NIH will hinder its ability to do the breakthrough work which is its raison d’etre. Then-Director of NIH Francis Collins countered the concerns citing NIH’s experience responding to the COVID-19 pandemic and expressing confidence that NIH can adopt “a DARPA attitude” in establishing and operating ARPA-H.

[If you want to dig deeper into the governmental processes at work here, you might listen to the hearing of the US House of Representative’s Energy and Commerce Committee on ARPA-H.]

What will ARPA-H do?

According to a document released by the White House, ARPA-H will be part of NIH, but will not be situated on the main campus of NIH in Bethesda, Maryland, so as to facilitate the development of a distinct work culture.

It elaborates thus:

Why can’t NIH just do this kind of work?

ARPA-H programs and projects will employ a radically different approach, culture, and organization, embracing a DARPA-like model of innovation and accountability. Whereas most NIH proposals are ‘curiosity-driven’, ARPA-H ideas will be largely ‘use-driven’ research — that is, research directed at solving a practical problem.

NIH has some experience with running large, complex programs using DARPA-like approaches to drive highly managed, use-inspired, breakthrough research. Recently, the NIH Rapid Acceleration of Diagnostics (RADx) initiative utilized an innovation funnel approach to rapidly advance promising COVID-19 diagnostic technologies. Looking further back, the Human Genome Project was an ambitious, bold, and long-term commitment to sequence the human genetic code that was completed ahead of schedule and has resulted in dramatically decreased costs of sequencing a human genome.

While these examples are compelling, they required ad hoc approaches. Future advances for diseases, ranging from rare to common, would each benefit from being pursued with this level of ambition. ARPA-H would allow NIH to pursue these needs systematically with an organization that is built for the purpose.

The same document also adds these details about the mission of ARPA-H is “to benefit the health of all Americans by catalyzing health breakthroughs that cannot readily be accomplished through traditional research or commercial activity”:

What gaps in the biomedical ecosystem is ARPA-H aiming to fill?

The current biomedical research ecosystem has historically been driven by two components:

• the important fundamental research, largely supported by NIH, a component of HHS, that has made great progress in uncovering the underlying mechanisms of health and disease
• the vibrant biopharmaceutical industry that has created products for patients in a multitude of disease areas

Often a critical gap remains. Some of the best ideas, which could yield bold breakthroughs, do not fit well into either half of our current system, because:

• the risk is too high
• the cost is too large
• the time frame is too long
• the focus is too applied for academia
• there is a need for complex coordination among multiple parties
• the near-term market opportunity is too small to justify commercial investment
• the scope is so broad that no company can realize the full economic benefit

The purpose of ARPA-H will be to support promising opportunities that fall in this gap.

What types of projects could ARPA-H support?

ARPA-H could fund programs and projects that undertake challenges ranging from the molecular to the societal, with the potential to transform entire areas of medicine and health by:

• Tackling bold challenges requiring large scale, sustained coordination, including those which span equities across the US government
• Creating new capabilities (e.g., technologies, data resources, disease models)
• Supporting high-risk exploration that could establish entirely new paradigms
• Overcoming market failures through critical solutions, including financial incentives

Whereas most NIH proposals are “curiosity-driven,” ARPA-H ideas would be largely “use-driven” research—that is, research directed at solving a practical problem.

What are examples of transformative progress that ARPA-H could drive? 

ARPA-H has the potential to accelerate advances in a range of biomedical and health research areas and diseases – from cancer to hypertension to infectious diseases to population-level behavioral interventions. Some illustrative examples include:

Cancer and Other Chronic Diseases

• Vaccines that can prevent most cancers. Use messenger RNA (mRNA) vaccines to teach the immune system to recognize any of 50 common genetic mutations that drive cancers, so that the body will wipe out cancer cells when they first arise.
• New manufacturing processes to create patient-specific T-cells to search and destroy malignant cells, decreasing costs from $100,000s to $1000s to make these therapies widely available.
• Molecular ‘zip codes’ that target a drug or gene therapy vector to any specific tissue and cell type, to make treatments much more effective by treating diseases at their source and eliminating side effects due to consequences in other tissues.
• Small, highly accurate, inexpensive, non-intrusive, wearable 24/7 monitors (e.g., smart watches) for blood pressure and blood sugar.
• New approaches to accelerate discovery of brain imaging and blood biomarkers capable of measuring synaptic loss, neuronal death, and glial inflammatory pathways, as a means of tracking responses to potential Alzheimer’s disease therapies.

Healthcare Access, Equity and Quality

• Platforms to reduce health disparities in maternal morbidity and mortality, which are among the highest in the world, by identifying those at highest risk for pregnancy complications and providing ethically-integrated, regular virtual house calls by nurses and midwives, from early in pregnancy through at least 6 months postpartum.

• Platforms to promote better health outcomes through substantially improving how medication is taken, as recommended, on a regular basis or over a standard course (e.g., for hypertension, diabetes, infections), by engaging community health workers aided by privacy-preserving smart devices and telehealth.

What’s the bottom line for non-dilutive funding?

The White House document quoted above says that, like DARPA, ARPA-H will not have an “a typical, standing intramural program.” This is in contrast, for example, with the Congressionally Directed Medical Research Programs (CDMRP). While DARPA and CDMRP both offer important funding opportunities, there are important differences. So it seems ARPA-H may be more akin to DARPA and less like its cousin CDMRP. That makes sense since if both ARPA-H and CDMRP (and NIH and the FDA…) address health issues, they ought to address different health issues or address them in different ways.

At this point, the details of ARPA-H’s funding model have not been defined, but if the funding model of DARPA serves as a template, it’s worth noting the following:

• DARPA publicizes funding opportunities primarily through Broad Agency Announcements (BAAs) which request proposals in specific R&D
• Each DARPA office (Biological Technologies, Defense Sciences, Information Innovation, etc.) has an “office-wide” BAA which is less specific in the kinds of R&D it supports.
• Open BAAs allow researchers to promote what they feel should be top priority R&D for the nation, even though those ideas fall outside of DARPA’s current priorities.
• DARPA awards Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants.
• DARPA’s Young Faculty Award program offers funding to promising junior faculty members and their peers at nonprofit research institutions.

The White House document also makes a point of reassuring us that ARPA-H will not take funding away from other NIH programs:

Will funding ARPA-H take funding away from other health initiatives at NIH?

We strongly believe that ARPA-H should not detract from what we know is already working well across NIH. So, ARPA-H funding should be complementary to and distinct from ongoing NIH and other agency efforts in a way that strengthens and helps catalyze transformative discoveries.

Indeed, Congress made good on that statement in its allocations increasing NIH’s budget even while establishing ARPA-H.