November 4, 2021: Accelerating Health Solutions for All: Reflections on NCATS and ARPA-H

The scientific, policy, and patient communities are abuzz about the President’s proposal for a new medical research agency, the Advanced Research Projects Agency for Health (ARPA-H). There is much to be excited about. NCATS comes up a lot in the conversation about ARPA-H. As I look forward to its establishment and think about NCATS’ 10-year anniversary, I find myself reflecting on the creation of NCATS and the experience gained over the past decade.

Like ARPA-H, NCATS was sparked by the energy of patients and families frustrated by the slow pace and high failure rate of drug development. The Center opened its doors in 2011 to make translational research more predictive and to address long-standing crimps in the therapy-development pipeline. At that time, the NIH director wrote, “The new center will … seek to invest in the kind of science that creates powerful new tools and technologies that can be adopted widely by researchers in public and private sectors to streamline and derisk the therapeutic development process.”

Our mission has remained focused on speeding the translation of scientific discoveries into health solutions. NCATS’ approach touches each stage along the path — from the biological and chemical basis of disease to the clinical approaches of interventions that improve health and reach those who need them. Our superpower is to address significant roadblocks in the translational process to accelerate progress across research areas and diseases by developing, disseminating and deploying platforms, tools and resources.

The seeds for NCATS’ crosscutting innovations were planted before the Center’s existence. Through patient-driven legislative proposals by Sen. Joe Lieberman in 2005 (American Center for Cures Act) and later by Sen. Arlen Specter (Cures Acceleration Network Act), NIH received authorization for the Cures Acceleration Network (CAN). CAN, which was included as part of NCATS’ portfolio, provides the Center with authorities and award mechanisms to promote flexibility and to fund innovative research that addresses “high-need cures” — defined as “a priority to diagnose, mitigate, prevent, or treat harm from any disease or condition” and also those “for which the incentives of the commercial market are unlikely to result in its adequate or timely development” — with tremendous potential to accelerate translation to benefit health.

NCATS and CAN were inspired by the very first “ARPA” — the Defense Advanced Research Projects Agency (DARPA). One of NCATS’ early CAN-supported programs, the Tissue Chip for Drug Screening program, was launched in collaboration with DARPA. Since then, the program has taken tissue chips to new heights: the International Space Station, where they are being used to study treatments for aging-related disorders. Along with our 3-D Tissue Bioprinting Program, the tissue chip program will provide new tools to increase the predictability of toxicity and efficacy during preclinical drug development. A newer CAN program, the Biomedical Data Translator, has shown great promise in enabling the rapid scouring of public information across existing databases to see connections that accelerate therapeutics discovery and testing. Then there is the NCATS-led Platform Vector Gene Therapy (PaVe-GT) pilot project and a newly formed cousin — the Bespoke Gene Therapy Consortium (BGTC), part of the NIH Accelerating Medicines Partnership — which are bringing innovations and accessible protocols into gene therapy platform strategies to benefit multiple rare diseases.

These innovative programs have the potential to address hundreds of high-need diseases currently lacking safe and effective treatments, but their scope and scale are limited by restrictions imposed on NCATS. The original CAN budget as envisioned by its advocates was $1 billion per year, but that was never realized. Today, NCATS supports CAN from its own appropriation to a limit of $60 million per year. This restriction requires us to make hard choices when deciding to launch or expand a CAN project. The budget also reduces the ability to use CAN’s DARPA-like authorities, such as use of other transactions and matching funds. In addition, the Center is not allowed to conduct clinical trials beyond Phase 2b, further limiting its ability to transform and improve the clinical trial processes. If ARPA-H is to be successful, it cannot have these sorts of restrictions; it needs to be fully resourced to ensure an unencumbered ability to work across the biomedical ecosystem.

ARPA-H has a bold and exciting agenda to bring more treatments to all people in a holistic way, cutting across all sectors of the biomedical ecosystem. Getting it right will require several key considerations, and NCATS can provide some lessons and continue to remain an important part of developing health solutions.

As I shared during my remarks at one of the OSTP-NIH listening sessions, ARPA-H should not merely speed up the way we have always done things. It must create entirely new ways of delivering therapies and health care innovations to patients while enabling the entire biomedical ecosystem to be more efficient. ARPA-H should deliver platform technologies that are ready to scale, like those being developed in gene-targeted therapies and in electronic health record research enabled by the National COVID Cohort Collaborative. ARPA-H must have the appropriate statutory authorities and the clarity of mission to ensure its innovations are implemented effectively across society.

Success also will require absolute clarity about who is doing what and what problems are uniquely “ARPA-able.” Benefits must be shared with members of racial and ethnic minority groups, so that all Americans receive cures and therapies. We all need to know our swim lanes; and if we occupy the same lane, we need it to be a perfect, well-coordinated relay. And, finally, ARPA-H’s architects have proposed that the agency have a distinct culture from NIH, similar to that proposed by NCATS’ early designers, who urged that “NCATS and CAN will be countercultural, with a different culture than the rest of NIH.” This has been critical for NCATS’ ability to be risk-taking and solution-focused.

NCATS has developed research prototypes the community can build upon and use to hit the ground running. We look forward to welcoming ARPA-H and stand ready to work together to honor the President’s resolve that the benefits of medical science and our health care system be accessible to people from all walks of life.

Your partner in science and health,

Joni L. Rutter, Ph.D.
Acting Director
National Center for Advancing Translational Sciences