Vanderbilt Health has been awarded a federal contract providing up to $11.2 million over five years to establish and operate a first-of-its-kind critical illness clinical trials acceleration platform aimed at improving outcomes for patients in the ICU.
Each year, more than 4.6 million people in the United States are treated in hospital intensive care units for critical illnesses and injuries that can trigger life-threatening immune and inflammatory responses.
Yet because clinicians cannot accurately track these responses, their ability to intervene quickly and precisely enough to prevent organ damage or death is limited. A federal program called CIRCLE—the Critical Illness Immunological Reprogramming and Control Point Learning Engine — is designed to change that.
A funded program of the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, CIRCLE will harness advances in diagnostics and artificial intelligence (AI) to speed development of next-generation interventions that identify and respond to harmful immunoinflammatory states before life-threatening complications occur.
That’s where Vanderbilt Health comes in. A leader in large-scale clinical trials, learning health systems, and translational research, Vanderbilt Health will create a platform for testing and validating new technologies, including immune-modulating therapeutic strategies, developed through the nationwide CIRCLE program.
The Vanderbilt-led effort is called the Goldilocks Program, for Groundbreaking Organization Leveraging Data Insights: Learning for Optimized Critical care Knowledge and Systems. If successful, it will help move critical care toward a predictive, precision-based field that identifies and corrects dangerous immune system dysregulation before irreversible organ injury occurs.
“CIRCLE represents an unprecedented opportunity to fundamentally change how we understand, monitor and treat critical illness,” said Wesley Self, MD, MPH, Senior Vice President for Clinical Research at Vanderbilt Health and project lead for this award.
“Our role is to ensure that promising innovations can move efficiently from development into clinical testing, generating the high-quality evidence necessary for adoption in real-world ICUs and ultimately improving outcomes for patients nationwide,” said Self, Professor of Emergency Medicine and Director of the Vanderbilt Institute for Clinical and Translational Research (VICTR).
The program brings together nationally recognized expertise in critical care medicine, clinical trials, biostatistics, implementation science, AI, biomedical informatics, commercialization and regulatory science. Investigators will assess technologies in simulated and real-world ICU environments, facilitate pilot studies, conduct adaptive clinical trials, and generate evidence suitable for regulatory review and transition to commercial adoption.
Currently it takes 12 to 18 months to move new health technologies from the readiness stage to first-in-patient testing. Goldilocks is designed to reduce that timeline to fewer than 90 days by providing continuous feedback, testing, validation and clinical guidance throughout development.
In addition to Self, key members of the Vanderbilt team leading this program include:
- Matthew Semler, MD, MSCI, Professor of Medicine, Melinda Owens Bass Chair in Medicine Chair, and Director of the Vanderbilt Center for Learning Healthcare
- Mayur Patel, MD, MPH, Professor of Surgery, Ingram Chair in Surgical Sciences, and Chief of the Division of Acute Care Surgery
- Jill Pulley, MBA, Executive Director of VICTR, and Research Professor of Medicine
- Jillian Rhoads, PhD, Clinical Scientist, VICTR
- James Weimer, PhD, Assistant Professor of Computer Science and Biomedical Engineering
Major collaborating and subcontracting partners who will be working with Vanderbilt Health on this project include:
- Nima Akhlaghi, PhD, Director of Digital Health & Imaging Center Lead at MCRA, a clinical research organization, and a former reviewer for the U.S. Food and Drug Administration
- Michelle Gong, MD, MSc, Chair of Medicine and Director of Critical Care Research, Montefiore Einstein in New York
- Carolyn Calfee, MD, MAS, Co-founder and Director of the Center for Precision Research in Critical Care, University of California, San Francisco
- Adit Ginde, MD, Senior Associate Dean for Clinical Research and Assistant Vice Chancellor for Clinical Trials, University of Colorado Anschutz School of Medicine
- Clifton Calloway, MD, PhD, Director of the University of Pittsburgh Clinical and Translational Science Institute, and Ronald D. Stewart Chair of Emergency Medicine Research
- Goldilocks will additionally engage a network of up to 25 participating institutions and more than 100 intensive care units across the United States to support product testing, validation studies and adaptive clinical trials.
Program investigators believe CIRCLE will lay the foundation for a future in which advanced diagnostics and precision immunomodulatory therapies become an integral part of critical care medicine.
“Critical illness remains one of the most complex and deadly challenges in medicine,” Self said. “This award positions Vanderbilt and our national partners to help create a new era of precision critical care that is smarter, faster, and more effective for patients and families.”
This research was, in part, funded by the Advanced Research Projects Agency for Health (ARPA-H). The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the United States government.
