The National COVID Cohort Collaborative (N3C) represents a transformative resource in health data research, empowering investigators to uncover critical insights and advance patient care. At the Center for Clinical and Translational Science (CCTS) and across our Partner Network, researchers are leveraging N3C’s unprecedented data repository to address complex health challenges and foster collaboration.

What is N3C?

N3C, established under the stewardship of the Center for Data to Health and the National Center for Advancing Translational Sciences (NCATS), brings together electronic health records (EHRs) from over 75 institutions, harmonizing them into a secure enclave for collaborative research. Originally designed to study COVID-19, N3C’s infrastructure now supports research across a growing array of health conditions, as reflected in its new moniker, the National Clinical Cohort Collaborative (N3C)

Key features of N3C include:

• Collaborative Data Enclaves | A centralized platform for analyzing de-identified patient data.
• Extensive Data Integration | Connections to additional datasets, creating a more complete picture of health outcomes.
• Secure and Compliant | Ensures privacy through stringent security measures and oversight

Researchers across the CCTS Partner Network are using N3C to explore topics such as disease progression, treatment efficacy, and the impact of social determinants of health.

N3C Research in Action

At the CCTS Hub and beyond, N3C has been a catalyst for impactful research. Below are just a few highlights of how investigators are using this resource to drive discovery.

• Predicting Long COVID Risks | Dr. Rena C. Patel and team used machine learning algorithms within the N3C enclave to study predictors of long COVID. Analyzing data from over 55,000 patients, they identified that the frequency of healthcare visits before infection was a stronger predictor of long COVID risk than other factors. Their findings provide a foundation for early interventions and preventive care for high-risk populations. Read more.
• Improving EHR Usability with Ontologies | Dr. James J. Cimino, Chair of the Department of Biomedical Informatics and Data Science, assisted with research to address the limitations of current EHR systems. By developing a Clinical Context Ontology (CCO), Dr. Cimino’s team introduced a Patient-Specific Knowledge Base (PSKB) that captures the “why” behind clinical decisions. This innovation simplifies navigation and enhances decision-making by presenting patient data in a semantically organized format. The CCO approach, tested using real-world N3C data, has the potential to reduce documentation burden and improve clinical care. Read more.
• Understanding COVID-19 Outcomes in Patients with Cancer | Dr. Noha Sharafeldin and colleagues conducted a groundbreaking study on cancer patients with COVID-19 using N3C. They identified demographic and clinical factors, such as age, geographic location, and recent cytotoxic therapy, associated with increased mortality risk. This research provides actionable insights for tailoring care strategies for cancer patients during pandemics. Read more.
• Analyzing the Impact of Background Medications | At Louisiana State University Health Sciences Center, a CCTS Partner Institution, Dr. Lucio Miele and team conducted research investigating how chronic anti-inflammatory medications influenced COVID-19 outcomes. His team's study highlighted the importance of integrating medication history into risk assessments and demonstrated the power of collaborative, multi-site analyses facilitated by N3C.

Overcoming Challenges and Building Opportunities

While N3C’s expansive dataset offers transformative research opportunities, analyzing real-world data requires addressing challenges such as data quality and completeness. Researchers across the CCTS Partner Network emphasize the critical role of team science and rigorous methodologies in ensuring reliable and impactful results. At a recent CCTS Data2Discovery Special Interest Group event, CCTS investigators shared insights into using the N3C enclave, including strategies for collaboration, data harmonization, and navigating the complexities of real-world datasets. These discussions exemplify how the Partner Network facilitates shared learning and resource optimization.

Expanding Opportunities with N3C

While created for COVID-19 research, N3C also supports investigations into a broad spectrum of health conditions. This expansion opens new opportunities for researchers to:

• Study the impact of social determinants of health
• Develop advanced predictive algorithms for disease outcomes
• Foster interdisciplinary collaborations across institutions

Dr. Haendel, a founding director of N3C, says that “one of the most rewarding aspects of N3C is how so many investigators of different backgrounds, skill sets, and career stages have come together to ask innovative and pivotal questions. N3C is team science at scale and it is not only incredibly effective, it is fun.”

Get Involved with N3C

Whether you are based at the CCTS Hub or one of our Partner Network institutions, the N3C enclave is a resource for accelerating research and discovery. To learn more about accessing N3C data, finding partners or technical support, or joining collaborative projects, contact the CCTS or visit the N3C website. Together, we can leverage this powerful tool – and community - to advance translational science and improve human health. Subscribe to the weekly CCTS Digest and connect with us on LinkedIn to stay informed of all upcoming CCTS events.