N3C publishes 2023 Year In Review

The National COVID Cohort Collaborative (N3C) offers one of the largest collections of secure and deidentified clinical data in the United States for COVID-19 research. With stewardship from NCATS, more than 75 institutions worked together to build this extensive database. The large, centralized data resource allows research teams to study COVID-19 and identify potential treatments.

The past year has been a testament to collaborative team science and realizing accessible real-world data—and the community has made terrific progress in planning for the future. N3C’s achievements include:

Substantial Collaborative Team Science Growth

In 2023, the N3C community grew to 4,953 (+1,597) registered users from 369 institutions. N3C now has 33 domain teams, 516 project teams, over 29 billion rows of data, and 234 sites contributing data. This group of clinicians, analysts, researchers, informaticians, patients, students, industry, government, and citizen scientists collaborates to create impactful public outcomes with N3C data.

Research Discoveries and Innovations

N3C's commitment to providing real-world, accessible, harmonized, and secure clinical data has resulted in several enclave enhancements that empowered researchers to address the most pressing clinical questions. N3C successfully integrated Centers for Medicare and Medicaid Services (CMS) data, patient de-duplications functionality, geocoded data, computable phenotypes, additional concept sets, and a plethora of new tools to aid in researcher analysis including a template for protocol design (Protocol Pad), a method to search, update, review and compare concept sets (TermHub), a Large Language Model designed to make searching for governance and resources easier (N3C Assist), and the addition of Jupyter notebooks (JupyterLab).

The N3C data and capabilities lead to research discoveries including:

• De-black-boxing health AI: demonstrating reproducible machine learning computable phenotypes using the N3C-RECOVER Long COVID model in the All of Us data repository ^*
• Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program ^*
• SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study ^*
• What causes long COVID? The answer might be in your gut
• Who is pregnant? Defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C)

^* UNC-Chapel Hill (specifically Emily Pfaff, PhD) was a lead or contributor on these papers.

Publications, Recognition, and Impact

N3C data was highlighted in research publications across prestigious academic journals, the scientific community, congressional documents, ARPA-h funding announcements, and among the press. In addition, N3C was consulted for policy and decision-making at the local and national levels. N3C was also recognized through various industry and institutional awards.

Many N3C community members attended various events throughout the year where they shared their research, participated in panel discussions, and presented on topics within the informatics and data science space.

Real World Data Training Including Claims Data

N3C understands the learning curve involved in Real World Data analysis and interpretation and has provided the community with resources to make them successful. In 2023, N3C trained the community on how to use Claims Data and released The Researcher’s Guide to N3C, a collaborative publication that acts as a guide for researchers conducting research in the N3C enclave. In January 2024, the N3C Education & Training Domain Team released a new short course, Introduction to Analyzing Real-World Data Using the National COVID Cohort Collaborative.

Together with the CTSA Workforce Development Enterprise Committee, the N3C is also planning several workshops to train-the-trainer on RWD analytics and a second hands-on training event for trainees that can be applied to any local or national RWD activity. Stay tuned for an announcement.

Paving the Path Forward

N3C hopes to build on the amazing accomplishments and incredible hard work of the CTSAs represented. The National Center for Advancing Translational Sciences (NCATS) is committed to open science, equity, accessibility, inclusiveness, and “more treatments for all people more quickly.

In 2023, N3C piloted a tenant model approach they are coining N3C Clinical. A tenant is a domain-specific harmonized data enclave. NCATS invited 12 volunteer organizations to pilot the use of N3C-style Enclave infrastructure with non-COVID data for specific research domains other than COVID; this included the submission of new limited datasets using a new, different Data Partnership Agreement between NCATS and the institutions providing the data and conducting the project (no data from N3C was used in the pilot).

The pilot involved 3 non-COVID projects: Alzheimer’s Disease and Related Dementias, Renal disease, and Chronic Obstructive Pulmonary Disease. The purpose of the N3C Clinical Tenant pilot was to test and document the feasibility of repurposing the infrastructure for NON-COVID Real World Data (RWD) research. The remit included estimates of future costs, the ability to establish efficient, scalable community governance and data contribution processes supporting multiple research enclaves, and the ability to provide researchers with agency and a secure computing platform to conduct analyses to address local and national questions.

All 10 data-contributing sites completed the IRB processes, 9 of the 10 successfully submitted data, and 11 sites successfully participated in the pilot projects. The initial pilot was a success! Plans are now in place to expand the tenant pilot to additional projects. Governance policies established by the community have secured organization-level autonomy and agency over how data will be used. New tenant pilots will include Education & Training, Renal (pending), and Cancer projects.

The Education & Training Tenant is a partnership with the NIH AIM-AHEAD program and hopes to create a comprehensive virtual research environment using synthetically derived datasets that provides open access for collaborative analytics environments for educators across CTSAs, AIM-AHEAD, and beyond to teach, develop, and share educational material on RWD science. The Renal (pending) and Cancer tenants will test feasibility of linking data from multiple government agencies and sources to generate a comprehensive data enclave. Please let NCATS know if you have ideas for future research domains and tenants.

As the N3C celebrates its success, the leadership team acknowledges the contributions of each member of N3C community and the role each played in program’s success. Here's to many more years of pioneering success and innovation in collaborative analytics and Real World Evidence generation!

N3C Leadership:
Melissa Haendel
Chris Chute
David Eichmann
Emily Pfaff
Richard Moffitt
Anita Walden