ARPA-H launches program to revolutionize critical care and help prevent life-threatening events

New CIRCLE program will transform how physicians care for the 4.6 million Americans who face potentially fatal critical illness in intensive care units each year 

The Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services (HHS), today announced the launch of its Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) program, a leading-edge initiative to better track the body’s immune response during critical illness so care clinicians can personalize treatments and save lives.  

Critical illness impacts more than 7 million Americans annually and can be caused by a variety of factors, from infections to severe injuries to chronic disease. These life-threatening conditions require stay in an intensive care unit (ICU) and lead to high morbidity and mortality among Americans—in some cases as high as 30%. The body’s immune response is pivotal in fighting disease; however, when immune and inflammatory responses go into overdrive these normally beneficial mechanisms can lead to worse health outcomes, like organ failure and death. 

“Too many families watch a loved one enter the intensive care unit and feel like they’ll never leave,” said ARPA-H Director Alicia Jackson, Ph.D. “With CIRCLE, we are aiming to change that. By harnessing cutting-edge artificial intelligence, advanced diagnostics, and real-time immune monitoring, this program will give ICU clinicians the tools they need to truly see what is happening inside the body during critical illness—and to act before it’s too late. CIRCLE reflects our commitment to turn 21st-century science into 21st-century care, so that when Americans face the worst health crisis of their lives, their doctors aren’t fighting blind, but are equipped with precise, life-saving insights.”  

Clinicians currently lack the tools to accurately track the body’s rapidly changing immune response and therefore cannot apply precision interventions to reduce inflammation before it damages organs.  CIRCLE aims to develop new digital capabilities using the latest in AI and diagnostics to better understand the role of the body’s immune response in critical illness and determine control points that can enable better use of existing immunotherapies as well as next-generation interventions for critical care.  

“Our body’s immune system is one the most powerful defenses against disease, but, because it is extremely fast-moving, complex, and imperfect it can paradoxically lead to worse outcomes.” said CIRCLE Program Manager Yoram Vodovotz, Ph.D. “CIRCLE seeks to unlock the ability to track and modulate the body’s immune response like never before and, in doing so, give clinicians the tools to prevent critical illness from claiming millions of lives.” 

The CIRCLE program has strict performance metrics and a focus on creating initial prototypes within 3-5 years. ARPA-H will solicit proposals under its Innovative Solutions Opening (ISO) in three phases: prototype research and development, computational and clinical evaluations of prototypes, and regulatory applications and clinical trials.

For more information, including solicitation details and Proposers’ Day registration, visit the CIRCLE program page.