The Researcher’s Guide to N3C

A National Resource for Analyzing Real-World Health Data


July 1, 2024




Welcome to The Researcher’s Guide to N3C: A National Resource for Analyzing Real-World Health Data. Here you will find guidance, information, and pointers to resources for conducting research with the National COVID Cohort Collaborative (N3C).

During a time of isolation and unanswered questions in an emerging pandemic, N3C was born of an urgent need to save lives. N3C was created “to acquire and harmonize data across organizations and provide a secure data environment to enable transparent and reproducible collaborative research.” 1 Dozens of technical, clinical, and regulatory experts from government agencies, healthcare organizations, academic institutions, and the private sector worked together to build the nation’s largest and most diverse set of de-identified health records to date. Today, thousands of researchers have actively engaged with N3C resulting in hundreds of scholarly products informing public policy and patient care.

N3C emphasizes community and team science values which are embodied by the structure of the organization and reflected in the following chapters. This guide originated as a project of the Education and Training Domain Team, one of the many self-organizing teams within N3C. An editorial committee was formed to engage with principal investigators, clinician-scientists, informaticians, data scientists, and others to condense the collective knowledge amassed in N3C. Chapters are authored and peer reviewed by a diverse group of contributors with both broad and deep domain expertise. This has been a work of heart and soul, designed to make this ground-breaking work accessible without obscuring its complexity.

N3C is continuously evolving, and we expect this book will as well. We invite you to join us in continually expanding and improving this guide, but most importantly, we invite you to get involved in one of the many avenues for impactful research that N3C provides.


The G2N3C Editorial Committee


Individual chapter lead and contributor affiliations are also provided in each chapter.

Editorial Committee
Shawn T. O’Neil, Will Beasley, Johanna Loomba, Sharon Patrick, Kenneth J. Wilkins, Karen M. Crowley

1  Introduction
Karen M. Crowley, Shawn T. O’Neil

2  A Research Story
Will Beasley, A. Jerrod Anzalone, Sharon Patrick

3  Data Life Cycle - From Patients to N3C Researchers
Stephanie Hong, Bryan Laraway, Xiaohan Tanner Zhang, Maya Choudhury, Sofia Z. Dard

4  Governance, Leadership, and Operations Structures
Christine Suver, Johanna Loomba

5  Onboarding, Enclave Access, N3C Team Science
Sharon Patrick, Jonathan F. Emery, Suzanne McCahan, Mary Helen Mays

6  Getting & Managing Data Access
Shawn T. O’Neil, Mariam Deacy

7  Understanding the Data
Harold P. Lehmann, Lisa Eskanazi, Sigfried Gold, Shawn T. O’Neil, Thomas Richards, Kristin Kostka

8  Introducing Enclave Analysis Tools
Amy Olex, Andrea G. Zhou, Johanna Loomba, Evan French, Shawn T. O’Neil, Steven G. Johnson

9  Best Practices for the Research Life Cycle
Harold P. Lehmann, Hytham Sidky, Jimmy Phuong, Kate Bradwell, Kenneth J. Wilkins, Andrea G. Zhou, David Sahner

10  Publishing and Sharing Your Work
Julie A. McMurry, Jeremy R. Harper, Christine Suver, Carolyn T. Bramante, Mary K. Emmett, Amit K. Saha, Farrukh M. Koraishy, A. Jerrod Anzalone, Shawn T. O’Neil

11  Help and Support
Shawn T. O’Neil, Saad Ljazouli, Johanna Loomba, Lisa Eskanazi

12  Machine Learning
Peter Robinson, Justin Reese

How to Contribute

We welcome suggestions, edits, and larger contributions to this guide. This book is typeset in Markdown, rendered with Quarto, and hosted on GitHub. For errors or requests, please submit an Issue to the book’s issue tracker. To make larger or direct contributions, please make a pull request using the standard GitHub workflow.

If you would like to contribute but are unfamiliar with any of these technologies, please feel free to email <to be created:> with comments and suggestions for changes. If you would like to discuss the content or receive further help, see the Help and Support Chapter.

This project uses the N3C Community Guidelines as a Contributor Code of Conduct; by participating in this project you agree to abide by its terms.

How to Cite this Work

O’Neil ST, Beasley W, Loomba J, Patrick S, Wilkins KJ, Crowley KM., Anzalone, AJ (Eds.) (2023). The Researcher’s Guide to N3C: A National Resource for Analyzing Real-World Health Data. DOI: 10.5281/zenodo.7749367

Editorial Committee:


This book is licensed under the Creative Commons Attribution-NoDerivatives 4.0. Individual chapters are as well, unless otherwise noted.


This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the N3C program.

Any analyses herein were conducted using the NCATS N3C Data Enclave supported by NCATS U24 TR002306, Axel Informatics Subcontract Number: NCATS-P00438-B and made possible because of the patients whose data was contributed by partner organizations. We gratefully acknowledge the scientists who have contributed to the on-going development of this community resource (Haendel et al. 2020).

Funding and support for individual authors is listed in 14  Funding and Institutional Support.

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