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The National COVID Cohort Collaborative (N3C):
Let’s Get Involved !
January 20, 2021
@data2health
@ncats_nih_gov
covid.cd2h.org
ncats.nih.gov/n3c
@wakibbe
Speaker Objectives
Warren Kibbe
Duke Biostatistics & Bioinformatics
CTSA Informatics
Duke Cancer Institute
Member N3C
● Overview of N3C
● N3C Data Enclave statistics
● How common data models and variables
are harmonized
● The scope of answerable questions
● Data access and security
● How common data models and variables
are harmonized
● Collaborative science in N3C
● User access and getting involved
A program of NIH’s National Center
for Advancing Translational Sciences
Clinical and Translational Science
Awards (CTSA) Program
Federated
querying
Data
resides
locally
Centralized
analytics
N3C
cloud
Data
resides
centrally in
a secure
enclave
Centralizing patient-
level data makes it
possible to ask different
and more powerful
questions than in
federated contexts
Such networks are key
to quickly build a
centralized dataset
Secure, reproducible, transparent, versioned, provenanced, attributed,
and shareable analytics on patient-level EHR data
Collaborative
Analytics -
N3C Secure
Data Enclave
● Algorithms (diagnosis, triage, predictive, etc.)
● Drug discovery & pharmacogenetics
● Multimodal analytics (EHR, imaging, genomics)
● Interventions that reduce disease severity
● Best practices for resource allocation
● Coordinated research efforts to maximize efficiency and
reproducibility
These all require the creation
of a comprehensive clinical data set
The pandemic highlights urgent needs
A program of NIH’s National Center
for Advancing Translational Sciences
What Kinds of Questions Can N3C Address?
The scope and scale of the information in the platform
will support probing questions such as:
● What social determinants of health are risk factors for mortality?
● Do some therapies work better than others? By region? By demographics?
● Can we compare local rare clinical observations with national occurrences?
● Can we predict who might have severe outcomes if they have COVID-19?
● What factors will predict the effectiveness of vaccines?
● Can we predict acute kidney injury in COVID-19 patients?
● Who might need a ventilator because of lung failure?
A program of NIH’s National Center
for Advancing Translational Sciences
Cohort characterization objectives
To clinically characterize the N3C cohort
● Largest U.S. COVID-19 cohort to date (+ representative controls)
● Racially, ethnically, and geographically diverse
To develop and share validated, versioned OMOP representations of
common variables (labs, vital signs, medications, treatments)
To generate hypotheses to be tested within N3C and elsewhere
● Clinical phenotypes and trajectories
● Treatment patterns and response
● … and many others
?
+
A program of NIH’s National Center
for Advancing Translational Sciences
Benefits to Organizations
●Access to large scale COVID-19 data from across the nation
●Pilot data for grant proposals
●Opportunities for KL2 and TL1 and other scholars
●Team science opportunities for new questions and access to
Teams, statistics, machine learning (ML), informatics
expertise
●Learn ML analytics, NLP methods & access to tools, software,
additional datasets
A program of NIH’s National Center
for Advancing Translational Sciences
Step 4. Federated Analytics with HPC
Who is in the N3C?
The N3C Computable Phenotype
● At a high level, our phenotype looks for patients:
○ With a positive COVID-19 test (PCR or antibody) OR
○ With an ICD-10-CM code of U07.1 OR
○ Two or more COVID-like diagnosis codes (ARDS, pneumonia, etc.) during the
same encounter, but only on or prior to 5/1/2020
● Each one of these patients is then demographically matched to two patients with
negative or equivocal COVID-19 tests.
● Each site securely sends this set of patients, along with their longitudinal EHR
data from 1/1/2018 to the present, to the N3C on a regular basis.
Age 47
Gender M
Race Black
Ethnicit
y
Unknow
n
COVID Positive
Matching algorithm
Age 49
Gender M
Race Black
Ethnicit
y
Hispanic/
Latino
COVID Negative
Age 46
Gender M
Race Black
Ethnicit
y
Not
Hispanic
COVID Negative
A program of NIH’s National Center
for Advancing Translational Sciences
April May June July Aug Sept Oct Nov Dec Jan
200
500K
2M
N3C Timeline
1M
Kick off
DTA Done
IRB JHU
G-Suite
1st DTA
Palantir
Phenotype 1.0
17 DTAs
DUA Complete
CDMs Mapped
43 DTAs
4 DUAs
COC Complete
1st Manuscript
Domain Teams
48 DTAs
29 DUAs
DAC Charter
Initial Training
59 DTAs
88 DUAs
30 DURs
12 Sites Avail.
NIH IRB
Support Desk
Harm/QA Comp.
69 DTAs
116 DUAs
67 DURs
25 Sites Avail.
Synthetic Avail
73 DTAs
129 DUAs
103 DURs
34 Sites Avail.
201 Objects Va
PPRL Contract
75 DTAs
139 DUAs
140 DURs
36 Sites Avail.
1st IDeA CTR
Ext Data Set
Knowledge
Store
Cohort Paper
2.6
M
4 papers
submitted
15 papers in
Publication
committee
review
N3C Enclave Data Stats
Over Three Billion Rows
2.7 Million Patients
A program of NIH’s National Center
for Advancing Translational Sciences
7,200,000+
3.6M+ 8B+
Projected 75+
1231 participants and 91 projects! Go team!
https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories
Data Transfer Agreement Signatories
12/1/2020
73 DTA Signatories
Northwestern University at Chicago ᛫ Tufts Medical Center ᛫ Advocate Health Care Network ᛫ University of Alabama at Birmingham ᛫ Oregon Health & Science University ᛫
University of Washington ᛫ Stanford University ᛫ The University of Michigan at Ann Arbor ᛫ Children's Hospital Colorado ᛫ Duke University ᛫ Medical College of Wisconsin ᛫ The
Ohio State University ᛫ University of Nebraska Medical Center ᛫ University of Arkansas for Medical Sciences ᛫ George Washington University ᛫ Johns Hopkins University ᛫ West
Virginia University ᛫ Medical University of South Carolina ᛫ University of North Carolina at Chapel Hill ᛫ University of Virginia ᛫ The University of Texas Medical Branch at Galveston
᛫ University of Minnesota ᛫ University of Cincinnati ᛫ Columbia University Irving Medical Center ᛫ Cincinnati Children's Hospital Medical Center ᛫ Rush University Medical Center ᛫
Nemours ᛫ University of Wisconsin-Madison ᛫ The State University of New York at Buffalo ᛫ Washington University in St. Louis ᛫ University of Rochester ᛫ The University of
Chicago ᛫ University of Miami ᛫ The Scripps Research Institute ᛫ University of Texas Health Science Center at San Antonio ᛫ University of Kentucky ᛫ University of Illinois at
Chicago ᛫ Virginia Commonwealth University ᛫ Weill Medical College of Cornell University ᛫ Carilion Clinic ᛫ University Medical Center New Orleans ᛫ The University of Iowa ᛫
Emory University ᛫ Maine Medical Center ᛫ The University of Texas Health Science Center at Houston ᛫ Boston University Medical Campus ᛫ The University of Utah ᛫ University of
Southern California ᛫ George Washington Children's Research Institute ᛫ University of Colorado Denver I Anschutz Medical Campus ᛫ Mayo Clinic Rochester ᛫ The Rockefeller
University ᛫ Montefiore Medical Center ᛫ University of Mississippi Medical Center ᛫ University of Oklahoma Health Sciences Center, Board of Regents ᛫ University of
Massachusetts Medical School Worcester ᛫ Aurora Health Care ᛫ Penn State ᛫ University of New Mexico Health Sciences Center ᛫ NorthShore University HealthSystem ᛫ Wake
Forest University Health Sciences ᛫ Vanderbilt University Medical Center ᛫ Regenstrief Institute ᛫ Brown University ᛫ Stony Brook University ᛫ University of California, Davis ᛫ Yale
New Haven Hospital ᛫ Rutgers, The State University of New Jersey ᛫ MedStar Health Research Institute ᛫ Loyola University Chicago ᛫ Loyola University Medical Center ᛫
University of Delaware ᛫ Children's Hospital of Philadelphia
N3C Enclave Data Stats
pediatrics
A program of NIH’s National Center
for Advancing Translational Sciences
Predicting Clinical Severity using machine
learning (64 input variables)
The most powerful predictors are patient age and widely available
vital sign and laboratory values.
Cohort Characterization manuscript
Governing N3C Data
A program of NIH’s National Center
for Advancing Translational Sciences
Goal of the Data Use Agreement is Privacy Protection
to Promote broad access:
● COVID-Related research only
● NIH housed secure repository
● No re-identification of individuals or data source
● No download or capture of raw data
● Open platform to all researchers
● Investigator activities are recorded and can be
audited for security and reproducibility
N3C: Unique Data Use and Privacy
A program of NIH’s National Center
for Advancing Translational Sciences
N3C: Governance and Access
Data Levels to Access
Goal of the Data Use Agreement is Privacy Protection to Promote broad access:
● COVID-Related research only
● No re-identification of individuals or data source
● No download or capture of raw data
● Open platform to all researchers
● Security: Activities in the N3C Data Enclave are recorded and can be audited
● Disclosure of research results to the N3C Data Enclave for the public good
● Analytics provenance
● Contributor Attribution tracking
Data Use and Privacy
Harmonization of N3C Data
A program of NIH’s National Center
for Advancing Translational Sciences
Versioned data from all sources is combined into a target model (OMOP)
N3C Data Harmonization
PATIENT_ID DIAGNOSIS_ID DIAGNOSIS_
DATE
12345 7298374 6/1/2020
PATIENT_ID DIAGNOSIS_CD DIAGNOSIS_
DATE
6789 U07.1 2020-07-04
Both patients have COVID-19 diagnoses, but
a single query won't capture both of them.
Hospital A Hospital B
A program of NIH’s National Center
for Advancing Translational Sciences
Data Ingestion & Harmonization Pipeline
Up-to-date phenotype description will always be here.
Scripts for sites to extract data, customized for each data model, are here.
Field
Mappings
Value Set
Mappings
OMOP
data
Ingest
Server
N3C Release Data Set
Data Quality Checks
Final QC
A program of NIH’s National Center
for Advancing Translational Sciences
Step 4. Federated Analytics with HPC
Data Quality
When a site submits data, there are several data quality checkpoints:
● On submission: Are there formatting or other critical errors that prevent us
from loading?
● Post-submission: Do the data pass our basic quality and plausibility checks?
Reasons to go back to the site for fixes include:
Site data quality is evaluated by an interdisciplinary team three times per
week, resulting in daily communication with sites.
COVID tests are
missing / test
counts are
implausible
Lack of visits with
a COVID-19
diagnosis code
Inpatient visits are
not well-defined in
the data
Large amounts of
missing or non-
harmonizable data
A program of NIH’s National Center
for Advancing Translational Sciences
N3C Data Harmonization
Variable and concept set validation
Domain tables
(person, visit, time,
concept, value, unit)
Quality Control
visualizations
Code set
definition
in Atlas
Code set
definition in
N3C Enclave
Ingested
data
Unit
harmonization
8/31: 36 Variable code sets
‘version 1.0’
Creatinine in urine
is included with
blood/serum levels
No creatinine
from site XXX
Mass/volume
Mixed with molarity
Data element curation
A program of NIH’s National Center
for Advancing Translational Sciences
N3C Data Harmonization
Creatinine: units & lab code usage Asthma: code usage across sites
Data element curation
A program of NIH’s National Center
for Advancing Translational Sciences
Developing Common MetaVariables
Ben Amor
Palantir
Harold Lehmann
Johns Hopkins
● Transparent and collaborative environment where all contributions are acknowledged
● Provenance and reproducibility
● Promptly sharing research results with N3C users
● Publish in high-impact journals
● Attribution for all N3C artifacts
N3C Attribution and Publication Principles
Researchers, projects, and
artifacts are all linked
together in the enclave
using the Contributor
Attribution Model (CAM).
N3C Provenance, Transparency,
Attribution & Rapid Sharing
A program of NIH’s National Center
for Advancing Translational Sciences
Realizing Team Science
A program of NIH’s National Center
for Advancing Translational Sciences
Key functions can
nucleate projects:
● Education & training
● Biostatistics
● Study design
● Evaluation
● Informatics
● Clinical expertise
● Innovation &
commercialization
● Community &
partnerships
N3C Domain Team Expertise:
● Enclave technology
● Data model (OMOP)
● Terminologies
● Data quality
● Codesets, variables,
phenotype
● Using/parsing N3C data
● Workflows, methods,
algorithms
Roles
Ingredients (Methods, datasets, instruments)
Scientific questions
N3C team Science within & across institutions
https://covid.cd2h.org/domain-teams
CTSAs
Diabetes & Obesity Domain Team
John Buse
Kajsa Kvist
Trine Abrahamsen
Anna Kakhoska
UNC
PREMISE:
Novel antihyperglycemic
medications have associated
cardiorenal benefits and reduced
mortality in diabetes.
QUESTION:
How are anti-hyperglycemic
medications with established
cardiorenal and mortality benefits
associated with mortality among
patients with type 2 diabetes and
COVID-19, compared to commonly
used diabetes medications?
Carolyn
Bramante
Steve
Johnson
Richard
Moffitt
Tanner
Zhang
Stephanie
Hong
Harold
Lehmann
Davera
Gabriel
Janos
Hajagos
A Tsunami of Acute Kidney Injury
April 2020 May 2020
Kidney Domain Team
Sandeep
Mallipatu
Richard Moffit
Stony
Brook PREMISE:
Kidney Injury contributes importantly to
mortality and leads to long term
mortality.
QUESTIONS:
What factors predict kidney injury early?
Are there regional differences in AKI
incidence?
Is AKI incidence in COVID-19
decreasing?
What are the predictors of ESKD after
AKI?
Stephanie
Hong
https://covid.cd2h.org/kidney/
David H.
Ellison
J. Brian
Byrd
Chirag
Parikh
Farrukh
Koraishy
Faifan Liu
Ivonne
Schulman
Johns
Hopkins
N3C Collaborative Analytics Domain Teams
Each Domain Team enables researchers with shared clinical questions surrounding COVID-19 to:
A program of NIH’s National Center
for Advancing Translational Sciences
Examples of Collaborative
Analytical Domain Teams
Clinical topic Analytical questions
AKI/ARB/ACE How to predict which patients will develop AKI? Relationship between AKI, invasive ventilation, and mortality. How to predict
when AKI will progress to CKD? How do outcomes correlate with dialysis timing? Oxygenation? ACEI vs. ARBs vs. ARNI
differentiation?
Critical Care How to best prioritize limited resources? What predictors help define which patients will fare best with any given intervention?
Diabetes What is the association between HbA1c at baseline and COVID outcomes for patients with diabetes? Are outcomes equivalent
among patients with type 2 diabetes and COVID-19 using different anti-hyperglycemic medications? Relationship between
COVID correlated diabetes development/exacerbation and outcome and treatment response.
Imaging Integrative analysis of image and clinical data to predict outcome and treatment response.
Immunosuppressed/
compromised
How effective is convalescent plasma? What are the predictors of effectiveness?
Oncology What germ line mutations predispose cancer patients to severe COVID outcomes?
Pediatrics What endophenotypes exist for MIS-C patients? What are the consequences of childhood COVID infection? Can we build a
classifier to predict MIS-C?
Pregnancy Determine birth outcomes across COVID-19 severity, intervention, and vaginal versus c-section deliveries; postpartum morbidity
and complications in positive cases.
Social Determinants of
Health (SDoH)
Is there a racial disparity to access in testing? What is the transmission intensity among populations by race/ethnicity,
rural/urban, income, etc? Are there differences in therapy response?
Short/long term
Complications
Assess longer term conditions, complications, and health care utilization; do these patients have readmissions? What are their
outcomes?
Hypercoagulability Are there subsets of patients with COVID-19 that are are likely to develop hypercoagulability? Risk factors for
hypercoagulability? Does therapeutic enoxaparin or LMWH improve overall outcomes in patients with COVID-19?
A program of NIH’s National Center
for Advancing Translational Sciences
Domain Team - SDoH Example
Social Determinants of Health (SDoH) are:
“The circumstances in which people are born, grow up, live, work and
age, and the systems put in place to deal with illness. These
circumstances are in turn shaped by a wider set of forces: economics,
social policies, and politics.”
-- World Health Organization
A program of NIH’s National Center
for Advancing Translational Sciences
SDoH Domain Team Activities
A program of NIH’s National Center
for Advancing Translational Sciences
SDoH Domain Team Current Research Areas
A program of NIH’s National Center
for Advancing Translational Sciences
Domain Teams & Common Resources
To join Domain Teams & access N3C resources: https://covid.cd2h.org/enclave
A program of NIH’s National Center
for Advancing Translational Sciences
Approved Enclave Projects
https://covid.cd2h.org/projects
View the list of N3C Data Enclave Projects that have been approved by the Data Access Committee (DAC).
A program of NIH’s National Center
for Advancing Translational Sciences
N3C Data Access: Process
Data Use Request
HSP / Security Training
Data Use
Agreement
https://ncats.nih.gov/n3c/about/applying-for-access
A program of NIH’s National Center
for Advancing Translational Sciences
N3C Registration/Training
https://covid.cd2h.org/tutorials
Training Office Hours:
Tuesdays & Thursdays at 10-11 am PT/1-2 pm ET
Registration Required at this link
Orientation Video Coming Soon
Additional Training Tutorials available in the Enclave
Registration for Documents,
Meetings & the N3C Data Enclave
Requires Authentication
Enclave Checklist
A program of NIH’s National Center
for Advancing Translational Sciences
Associationbetween GLP1 receptor agonist (GLP1-RA) and sodium glucose co-transporter 2 inhibitor (SGLT2i) use and COVID-19 outcomes: A nationalretrospectivecohort
study
Simulationof existingFDA- approved active compoundsagainst COVID protein primary and sub-structures to interrupt protein activityfollowedby epidemiological, in-vitro and
in-vivo validation
Antibody response to SARS-CoV-2 in people with multiplesclerosis treated with B cell depleting therapies
Alcohol Use and Respiratory Outcomes in COVID19 Infections
Smoking and COVID-19 Outcomesin U.S. Adults (SCOTUS)
Validatea Machine Learning Model to Predict Decompensationin Patients with COVID-19
Workflow Constructionwith SyntheticData -Version 1
Understandingnon-invasiveventilationtreatment failuresin COVID-19
N3C Cohort Characterization
COVID-19 in individualswith Down's Syndrome
ExaminingAssociationsbetween VitaminD Status and COVID-19 Test Results
Identificationof Novel COVID-19 SubphenotypesUsing Temperature Trajectories
Identificationof Novel COVID-19 SubphenotypesUsing Temperature Trajectories
An evaluation of Direct Acting Anticoagulantsand Dexamethasonein Patientswith COVID-19 Infections
N3C Diabetes and Obesity Domain Team level 2 request for data
[N3C Operational] Data Ingestionand Harmonization
Studying COVID-19 Remission,Recrudescence, Recurrence, and Reinfection
[N3C Operational] Implementationof Syntegra SyntheticData Generator”
Impact of medicationon outcomesfor diabeticpatients
Monocytopeniain COVID-19
Acute Kidney Injury in Pediatric COVID-19 Patients
Using MachineLearning to differentiateCOVID-19 infectionwith seasonalflu
COVID-19 and Percutaneous CatheterizationInterventions: ModelingRisk of Serious Adverse Outcomes
COVID-19 infectionand mortalityamong individualswith disabilities
Deep learning of longitudinalchest X-ray and clinical variablesto predict needs for invasive mechanical ventilationand mortalityin COVID-19 patients
Continued In-HospitalACEi and ARB Use in HypertensiveCOVID-19 Patients
AI-AssistedAssessment,Tracking, and Reporting of COVID-19 Severity on Chest CT
Impact of COVID-19 infectionin patientswith pulmonary non-tuberculousMycobacterium (NTM) infection: A cohort study.
Disparitiesin COVID-19
[N3C Operational] CollaborativeAnalytics
BenchmarkingGenerative Adversarial Network (GAN) based synthetic EHR data generation methodsfor enabling COVID-19 research
Outcomes of Acute Pulmonary Embolismin COVID-19
[N3C Operational] SyntheticData ValidationUse Cases
N3C Pregnancy Task Team: COVID-19 Incidence, Treatment, and Outcomes in Pregnant Women
Contributionof Race and other Social Determinantsof Health to Disparitiesin Patient Outcomes in COVID-19
HospitalizationRates Feb-April vs May-October
The Effect of COVID-19 Stay-At-Home Orders on HemoglobinA1c Levels in DiabeticPatients
DevelopingDynamic Graphs for Predictionand Classificationof COVID-19 Patient Trajectories
Occurrence of neurologicaldiseases in hospitalizedpatientswith COVID-19 infection
COVID-19 and Air pollution
Towards the development of a learning health systemin the COVID-19 pandemic:analysis of patient data to assist clinicaldecisionmaking
ProtectiveEffects of MedicationsAgainst SARS-CoV-2 Infectionin Patientswith ExistingPrescriptions
Associationbetween glucagon-likepeptide 1 receptor agonist (GLP1-RA) and sodium glucose co-transporter 2 inhibitor (SGLT2i) use and COVID-19 outcomes: A national
retrospectivecohort study
MultiorganDysfunctionSyndrome and Complex Clinical Trajectory
Data-driven Investigationof Health Disparitiesin COVID-19 Outcomes: A Focus on Behavioral Health
Investigatingthe impact of biases on the performance of analytical models for COVID-19 related care.
Factors affectingrisk of poor outcomes for COVID-19 for patientswith diabetes
COVID-19 as a HeterogeneousProcess: Varying Underlying PathophysiologicalMechanismsat Different Time Points and Severities
Orthopaedic Surgery in the National COVID Cohort Collaborative(N3C)
Modelingof COVID-19 Risks for Back-to-Work Programs
COVID-19 impact on pregnancy and fetal wellbeing
Treatment associatedwith lower mortalityin hospitalizedCOVID-19 patients
Stage Aware Prediction of COVID19 Disease Progression
Stroke and COVID Population: An N3C and UVA OMOP analysis
Associationof Dupilumab with Protection from COVID-19 Respiratory Failure
CardiovascularComplicationsof COVID-19
Examiningthe dynamicsin social determinantsof health with regards to differential COVID-19 incidenceacross the United States
Use, Safety and Effectivenessof Therapies to Treat COVID-19
NIRVANA
Developingan applicationto predict the severity of COVID-19 infectionsof individual patientsby applyingartificial intelligencemethodologies
Developingan applicationto predict the severity of COVID-19 infectionsof individual patientsby applyingartificial intelligencemethodologies
N3C ImmunoSuppressed/CompromisedTask Team: The Impact of COVID-19 on the ISC Population
Epidemiologyof Acute and Chronic Kidney Injury Associated SARS-CoV-2 Infection
Analysisof Time Windows as Determining Factors for COVID-19 Patient Outcomes
AssessingTemporal Lab Value Changes and Medicationsas Predictors of Health Outcomes for COVID19+ Patients
[N3C Operational] Phenotype and Data AcquisitionTeam Operations
Retrospective identificationof medicationsto treat COVID-19
Adaptive and interpretablemachine learning to predict COVID-19 trajectory and severity
Case-Control Studies of Medicationsand Their Possible Associationswith COVID-19 Severity
HIV and COVID-19: Effect of Shelter-In-PlaceOrders on Virologic Suppression
Impactsof COVID -19 in Older Adults (Elder Impact Domain) Level 2
Impactsof COVID -19 in Older Adults (Elder Impact Domain)
Differential Clinical Outcomesfor Drug Repurposing Candidates Discovered in BSL3 SARS-CoV-2 InfectionModel
Study Phenotype of COVID-19 in Patients with Hemophilia: A NationalCohort Study
Neurological Manifestationof SARS-CoV-2 infection in African Americans: AI-based Novel Approach of Prognostic and Risk Stratification Models
Numerous
Projects
Numerous
People
Numerous
Institutions
Expertise &
Resources
Connected
91 Projects 1231 People 313 Institutions
A program of NIH’s National Center
for Advancing Translational Sciences
● N3C comprises the largest, most representative patient-level COVID-19
cohort in the US and continues to grow
● We CAN do transparent, reproducible, innovative science (including ML)
on sensitive observational data at scale, together!
● N3C is an innovative partnership between clinical sites, CDM
communities, NIH ICs, CD2H, and commercial partners
● Automation of data extraction and minimum requirements reduces
burden and increases site participation
● Robust attribution of all contributors; also provides great venue for
trainees
● N3C data is complicated, but there are many people and resources to
help users do good science
Step 4. Federated Analytics with HPC
Takeaways
A program of NIH’s National Center
for Advancing Translational Sciences
Register with N3C: https://labs.cd2h.org/registration/
Joining Workstreams:
N3C Data Ingestion & Harmonization Workstream
Slack Channel Harmonization
Google Group Harmonization
N3C Phenotype & Data Acquisition Workstream
Slack Channel Phenotype
Google Group Phenotype
N3C Collaborative Analytics Workstream
Slack Channel Analytics
Google Group Analytics
N3C Data Partnership & Governance Workstream
Slack Channel Governance
Google Group Governance
N3C Synthetic Clinical Data Workstream
Slack Channel Synthetic
Google Group Synthetic
N3C Implementation Workstream- Coming soon
Additional Information:
Onboarding N3C, Slack, Google | Finding and Joining a Google Group
NCATS N3C Webpage N3C Website
How to Get Involved with N3C
A program of NIH’s National Center
for Advancing Translational Sciences
COVID-19 Research Open House Week
January 19th-25th
Kick-off Event: Community Research Symposium
Tuesday January 19, 2021 | 9-10am PT/12-1pm ET
● Opening remarks from N3C leadership
● PI/Clinician Testimonial: David Ellison, MD
● Demonstration of the N3C Data Enclave
● Flash talks from the Pregnancy & Diabetes/Obesity Domain
Teams
● N3C Tutorial: How to Get Involved
Participating Meeting Schedule:
More Details:
https://covid.cd2h.org/n3c-openhouse
A program of NIH’s National Center
for Advancing Translational Sciences
Melissa A. Haendel,1,4,7,8,10,13,14,52,78,101 Christopher G. Chute,1,4,8,10,13,14,52,78,100,101 Tellen D. Bennett,9,10,13,14,52,100,101 David A. Eichmann,4,9,10,13,78,101 Justin
Guinney,4,9,10,14,78,101 Warren A. Kibbe,9,10,52,78,101 Philip R.O. Payne,4,9,10,78,101 Emily R. Pfaff,9,10,13,15,52,78 Peter N. Robinson,4,9,10,15,52,78,100 Joel H.
Saltz,10,13,14,15,52,78,101 Heidi Spratt,9,10,100 Christine Suver,10,78,101 John Wilbanks,10,78,101 Adam B. Wilcox,10,101 Andrew E. Williams,10,13,78 Chunlei Wu,9,13,14,78
Clair Blacketer,15,52 Robert L. Bradford,9,52 James J. Cimino,10,14,101 Marshall Clark,9,15,52 Evan W. Colmenares,9,15,52 Patricia A. Francis,78 Davera
Gabriel,9,10,13,14,15,52 Alexis Graves,7,9,78 Raju Hemadri,9,15,52 Stephanie S. Hong,9,15,52 George Hripscak,10,52 Dazhi Jiao,9,15,52 Jeffrey G. Klann,14,52,101 Kristin
Kostka,9,15,52 Adam M. Lee,9,15,52 Harold P. Lehmann,9,15,52 Lora Lingrey,9,15,52 Robert T. Miller,9,15,52 Michele Morris,9,15,52 Shawn N. Murphy,9,15,52 Karthik
Natarajan,9,15,52 Matvey B. Palchuk,9,15,52 Usman Sheikh,9,78 Harold Solbrig,9,15,52 Shyam Visweswaran,10,15,52,101 Anita Walden,7,10,13,14,52,101 Kellie M.
Walters,10,14,101 Griffin M. Weber,10,101 Xiaohan Tanner Zhang,9,15,52 Richard L. Zhu,9,15,52 Benjamin Amor,78 Andrew T. Girvin,15,78 Amin Manna,78 Nabeel
Qureshi,15,78 Michael G. Kurilla,10,78 Sam G. Michael,10,78 Lili M. Portilla,101 Joni L. Rutter,1,101 Christopher P. Austin,101 Ken R. Gersing,78,101
Shaymaa Al-Shukri,4,15 Adil Alaoui,101 Ahmad Baghal,15 Pamela D. Banning,15,100 Edward M. Barbour,8,15 Michael J. Becich,15,52,101 Afshin Beheshti,14 Gordon R. Bernard,8,15 Sharmodeep Bhattacharyya,100 Mark
M. Bissell,9,15 L. Ebony Boulware,14,100 Samuel Bozzette,100,101 Donald E. Brown,101 John B. Buse,14 Brian J. Bush,8,101 Tiffany J. Callahan,14,52 Thomas R. Campion,8,15 Elena Casiraghi,9,15 Ammar A.
Chaudhry,13,14 Guanhua Chen,9 Anjun Chen,13 Gari D. Clifford,8,15 Megan P. Coffee,14,100 Tom Conlin,14 Connor Cook,7,78 Keith A. Crandall,9,14,101 Mariam Deacy,78 Racquel R. Dietz,78 Nicholas J. Dobbins,8,9
Peter L. Elkin,15,52,100 Peter J. Embi,52,101 Julio C. Facelli,8,15 Karamarie Fecho,13 Xue Feng,9 Randi E. Foraker,8,13,15 Tamas S. Gal,8,15 Linqiang Ge,14 George Golovko,15,101 Ramkiran Gouripeddi,14,15 Casey S.
Greene,13,14 Sangeeta Gupta,52,101 Ashish Gupta,13,101 Janos G. Hajagos,9,15 David A. Hanauer,15,52 Jeremy Richard Harper,9,14,52 Nomi L. Harris,14 Paul A. Harris,101 Mehadi R. Hassan,9 Yongqun He,15,52,100
Elaine L. Hill,9,14 Maureen E. Hoatlin,14 Kristi L. Holmes,4,101 LaRon Hughes,14 Randeep S. Jawa,14 Guoqian Jiang,14 Xia Jing,7,14 Marcin P. Joachimiak,8,15 Steven G. Johnson,9,14,101 Rishikesan
Kamaleswaran,9,15,78 Thomas George Kannampallil,15,101 Andrew S. Kanter,15,52 Ramakanth Kavuluru,9,13,14 Kamil Khanipov,8,14 Hadi Kharrazi,9,14 Dongkyu Kim,15,52 Boyd M. Knosp,8,15 Arunkumar Krishnan,9
Tahsin Kurc,9,15 Albert M. Lai,101 Christophe G. Lambert,52,101 Michael Larionov,14 Stephen B. Lee,1,14 Michael D. Lesh,9 Olivier Lichtarge,14 John Liu,9 Sijia Liu,8,9,101 Hongfang Liu,9,15 Johanna J. Loomba,1,15,78,101
Sandeep K. Mallipattu,9,14,15 Chaitanya K. Mamillapalli,14 Christopher E. Mason,15 Jomol P. Mathew,8,15,52 James C. McClay,101 Julie A. McMurry,1,4,7,9,13,14,78 Paras P. Mehta,14 Ofer Mendelevitch,9 Stephane
Meystre,8,14,15 Richard A. Moffitt,9,13,15 Jason H. Moore,8,9 Hiroki Morizono,13,14,15,52 Christopher J. Mungall,15,52 Monica C. Munoz-Torres,7,10,78 Andrew J. Neumann,78 Xia Ning,14 Jennifer E. Nyland,13,14 Lisa
O'Keefe,78 Anna O'Malley,78 Shawn T. O'Neil,78 Jihad S. Obeid,10,14,15 Elizabeth L. Ogburn,13 Jimmy Phuong,9,15,52,100,101 Jose D Posada,8,15 Prateek Prasanna,14,52 Fred Prior,9,14,15 Justin Prosser,9,78 Amanda
Lienau Purnell,101 Ali Rahnavard,9,52 Harish Ramadas,9,52,78 Justin T. Reese,9,10 Jennifer L. Robinson,14,100 Daniel L. Rubin,101 Cody D. Rutherford,9,101 Eugene M. Sadhu,8,15 Amit Saha,9 Mary Morrison
Saltz,15,52,101 Thomas Schaffter,78 Titus KL Schleyer,14 Soko Setoguchi,8,14,15 Nigam H. Shah,8,14 Noha Sharafeldin,14 Evan Sholle,15,52 Jonathan C. Silverstein,15,52,101 Anthony Solomonides,101 Julian Solway,14,101
Jing Su,101 Vignesh Subbian,9,52,101 Hyo Jung Tak,15 Bradley W. Taylor,9,14 Anne E. Thessen,14,101 Jason A. Thomas,15 Umit Topaloglu,15,52 Deepak R. Unni,8,9,15,52 Joshua T. Vogelstein,14 Andréa M. Volz,7 David
A. Williams,14,15 Kelli M. Wilson,9,78 Clark B. Xu,8,9,15 Hua Xu,9,10,14 Yao Yan,9,15,52 Elizabeth Zak,8,15 Lanjing Zhang,101 Chengda Zhang,14 Jingyi Zheng,14
1CREDIT_00000001 (Conceptualization)4CREDIT_00000004 (Funding acquisition)7CRO_0000007 (Marketing and Communications)8CREDIT_00000008 (Resources)9CREDIT_00000009 (Software role)10CREDIT_00000010
(Supervision role)13CREDIT_00000013 (Original draft)14CREDIT_00000014 (Review and editing)15CRO_0000015 (Data role)52CRO_0000052 (Standards role)78CRO_0000078 (Infrastructure role)100Clinical Use Cases101Governance
https://academic.oup.com/jamia/advance-
article/doi/10.1093/jamia/ocaa196/5893482
Questions or Comments?
Thank you!
Thank you!
A program of NIH’s National Center
for Advancing Translational Sciences

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DCHI webinar on N3C January 2021

  • 1. The National COVID Cohort Collaborative (N3C): Let’s Get Involved ! January 20, 2021 @data2health @ncats_nih_gov covid.cd2h.org ncats.nih.gov/n3c @wakibbe
  • 2. Speaker Objectives Warren Kibbe Duke Biostatistics & Bioinformatics CTSA Informatics Duke Cancer Institute Member N3C ● Overview of N3C ● N3C Data Enclave statistics ● How common data models and variables are harmonized ● The scope of answerable questions ● Data access and security ● How common data models and variables are harmonized ● Collaborative science in N3C ● User access and getting involved A program of NIH’s National Center for Advancing Translational Sciences
  • 3. Clinical and Translational Science Awards (CTSA) Program
  • 4. Federated querying Data resides locally Centralized analytics N3C cloud Data resides centrally in a secure enclave Centralizing patient- level data makes it possible to ask different and more powerful questions than in federated contexts Such networks are key to quickly build a centralized dataset
  • 5. Secure, reproducible, transparent, versioned, provenanced, attributed, and shareable analytics on patient-level EHR data Collaborative Analytics - N3C Secure Data Enclave
  • 6. ● Algorithms (diagnosis, triage, predictive, etc.) ● Drug discovery & pharmacogenetics ● Multimodal analytics (EHR, imaging, genomics) ● Interventions that reduce disease severity ● Best practices for resource allocation ● Coordinated research efforts to maximize efficiency and reproducibility These all require the creation of a comprehensive clinical data set The pandemic highlights urgent needs A program of NIH’s National Center for Advancing Translational Sciences
  • 7. What Kinds of Questions Can N3C Address? The scope and scale of the information in the platform will support probing questions such as: ● What social determinants of health are risk factors for mortality? ● Do some therapies work better than others? By region? By demographics? ● Can we compare local rare clinical observations with national occurrences? ● Can we predict who might have severe outcomes if they have COVID-19? ● What factors will predict the effectiveness of vaccines? ● Can we predict acute kidney injury in COVID-19 patients? ● Who might need a ventilator because of lung failure? A program of NIH’s National Center for Advancing Translational Sciences
  • 8. Cohort characterization objectives To clinically characterize the N3C cohort ● Largest U.S. COVID-19 cohort to date (+ representative controls) ● Racially, ethnically, and geographically diverse To develop and share validated, versioned OMOP representations of common variables (labs, vital signs, medications, treatments) To generate hypotheses to be tested within N3C and elsewhere ● Clinical phenotypes and trajectories ● Treatment patterns and response ● … and many others ? + A program of NIH’s National Center for Advancing Translational Sciences
  • 9. Benefits to Organizations ●Access to large scale COVID-19 data from across the nation ●Pilot data for grant proposals ●Opportunities for KL2 and TL1 and other scholars ●Team science opportunities for new questions and access to Teams, statistics, machine learning (ML), informatics expertise ●Learn ML analytics, NLP methods & access to tools, software, additional datasets A program of NIH’s National Center for Advancing Translational Sciences
  • 10. Step 4. Federated Analytics with HPC Who is in the N3C? The N3C Computable Phenotype ● At a high level, our phenotype looks for patients: ○ With a positive COVID-19 test (PCR or antibody) OR ○ With an ICD-10-CM code of U07.1 OR ○ Two or more COVID-like diagnosis codes (ARDS, pneumonia, etc.) during the same encounter, but only on or prior to 5/1/2020 ● Each one of these patients is then demographically matched to two patients with negative or equivocal COVID-19 tests. ● Each site securely sends this set of patients, along with their longitudinal EHR data from 1/1/2018 to the present, to the N3C on a regular basis. Age 47 Gender M Race Black Ethnicit y Unknow n COVID Positive Matching algorithm Age 49 Gender M Race Black Ethnicit y Hispanic/ Latino COVID Negative Age 46 Gender M Race Black Ethnicit y Not Hispanic COVID Negative A program of NIH’s National Center for Advancing Translational Sciences
  • 11. April May June July Aug Sept Oct Nov Dec Jan 200 500K 2M N3C Timeline 1M Kick off DTA Done IRB JHU G-Suite 1st DTA Palantir Phenotype 1.0 17 DTAs DUA Complete CDMs Mapped 43 DTAs 4 DUAs COC Complete 1st Manuscript Domain Teams 48 DTAs 29 DUAs DAC Charter Initial Training 59 DTAs 88 DUAs 30 DURs 12 Sites Avail. NIH IRB Support Desk Harm/QA Comp. 69 DTAs 116 DUAs 67 DURs 25 Sites Avail. Synthetic Avail 73 DTAs 129 DUAs 103 DURs 34 Sites Avail. 201 Objects Va PPRL Contract 75 DTAs 139 DUAs 140 DURs 36 Sites Avail. 1st IDeA CTR Ext Data Set Knowledge Store Cohort Paper 2.6 M 4 papers submitted 15 papers in Publication committee review
  • 12. N3C Enclave Data Stats Over Three Billion Rows 2.7 Million Patients A program of NIH’s National Center for Advancing Translational Sciences 7,200,000+ 3.6M+ 8B+ Projected 75+ 1231 participants and 91 projects! Go team!
  • 13. https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories Data Transfer Agreement Signatories 12/1/2020 73 DTA Signatories Northwestern University at Chicago ᛫ Tufts Medical Center ᛫ Advocate Health Care Network ᛫ University of Alabama at Birmingham ᛫ Oregon Health & Science University ᛫ University of Washington ᛫ Stanford University ᛫ The University of Michigan at Ann Arbor ᛫ Children's Hospital Colorado ᛫ Duke University ᛫ Medical College of Wisconsin ᛫ The Ohio State University ᛫ University of Nebraska Medical Center ᛫ University of Arkansas for Medical Sciences ᛫ George Washington University ᛫ Johns Hopkins University ᛫ West Virginia University ᛫ Medical University of South Carolina ᛫ University of North Carolina at Chapel Hill ᛫ University of Virginia ᛫ The University of Texas Medical Branch at Galveston ᛫ University of Minnesota ᛫ University of Cincinnati ᛫ Columbia University Irving Medical Center ᛫ Cincinnati Children's Hospital Medical Center ᛫ Rush University Medical Center ᛫ Nemours ᛫ University of Wisconsin-Madison ᛫ The State University of New York at Buffalo ᛫ Washington University in St. Louis ᛫ University of Rochester ᛫ The University of Chicago ᛫ University of Miami ᛫ The Scripps Research Institute ᛫ University of Texas Health Science Center at San Antonio ᛫ University of Kentucky ᛫ University of Illinois at Chicago ᛫ Virginia Commonwealth University ᛫ Weill Medical College of Cornell University ᛫ Carilion Clinic ᛫ University Medical Center New Orleans ᛫ The University of Iowa ᛫ Emory University ᛫ Maine Medical Center ᛫ The University of Texas Health Science Center at Houston ᛫ Boston University Medical Campus ᛫ The University of Utah ᛫ University of Southern California ᛫ George Washington Children's Research Institute ᛫ University of Colorado Denver I Anschutz Medical Campus ᛫ Mayo Clinic Rochester ᛫ The Rockefeller University ᛫ Montefiore Medical Center ᛫ University of Mississippi Medical Center ᛫ University of Oklahoma Health Sciences Center, Board of Regents ᛫ University of Massachusetts Medical School Worcester ᛫ Aurora Health Care ᛫ Penn State ᛫ University of New Mexico Health Sciences Center ᛫ NorthShore University HealthSystem ᛫ Wake Forest University Health Sciences ᛫ Vanderbilt University Medical Center ᛫ Regenstrief Institute ᛫ Brown University ᛫ Stony Brook University ᛫ University of California, Davis ᛫ Yale New Haven Hospital ᛫ Rutgers, The State University of New Jersey ᛫ MedStar Health Research Institute ᛫ Loyola University Chicago ᛫ Loyola University Medical Center ᛫ University of Delaware ᛫ Children's Hospital of Philadelphia
  • 14. N3C Enclave Data Stats pediatrics A program of NIH’s National Center for Advancing Translational Sciences
  • 15. Predicting Clinical Severity using machine learning (64 input variables) The most powerful predictors are patient age and widely available vital sign and laboratory values. Cohort Characterization manuscript
  • 16. Governing N3C Data A program of NIH’s National Center for Advancing Translational Sciences
  • 17. Goal of the Data Use Agreement is Privacy Protection to Promote broad access: ● COVID-Related research only ● NIH housed secure repository ● No re-identification of individuals or data source ● No download or capture of raw data ● Open platform to all researchers ● Investigator activities are recorded and can be audited for security and reproducibility N3C: Unique Data Use and Privacy A program of NIH’s National Center for Advancing Translational Sciences
  • 19. Data Levels to Access
  • 20. Goal of the Data Use Agreement is Privacy Protection to Promote broad access: ● COVID-Related research only ● No re-identification of individuals or data source ● No download or capture of raw data ● Open platform to all researchers ● Security: Activities in the N3C Data Enclave are recorded and can be audited ● Disclosure of research results to the N3C Data Enclave for the public good ● Analytics provenance ● Contributor Attribution tracking Data Use and Privacy
  • 21. Harmonization of N3C Data A program of NIH’s National Center for Advancing Translational Sciences
  • 22. Versioned data from all sources is combined into a target model (OMOP) N3C Data Harmonization PATIENT_ID DIAGNOSIS_ID DIAGNOSIS_ DATE 12345 7298374 6/1/2020 PATIENT_ID DIAGNOSIS_CD DIAGNOSIS_ DATE 6789 U07.1 2020-07-04 Both patients have COVID-19 diagnoses, but a single query won't capture both of them. Hospital A Hospital B A program of NIH’s National Center for Advancing Translational Sciences
  • 23. Data Ingestion & Harmonization Pipeline Up-to-date phenotype description will always be here. Scripts for sites to extract data, customized for each data model, are here. Field Mappings Value Set Mappings OMOP data Ingest Server N3C Release Data Set Data Quality Checks Final QC A program of NIH’s National Center for Advancing Translational Sciences
  • 24. Step 4. Federated Analytics with HPC Data Quality When a site submits data, there are several data quality checkpoints: ● On submission: Are there formatting or other critical errors that prevent us from loading? ● Post-submission: Do the data pass our basic quality and plausibility checks? Reasons to go back to the site for fixes include: Site data quality is evaluated by an interdisciplinary team three times per week, resulting in daily communication with sites. COVID tests are missing / test counts are implausible Lack of visits with a COVID-19 diagnosis code Inpatient visits are not well-defined in the data Large amounts of missing or non- harmonizable data A program of NIH’s National Center for Advancing Translational Sciences
  • 25. N3C Data Harmonization Variable and concept set validation Domain tables (person, visit, time, concept, value, unit) Quality Control visualizations Code set definition in Atlas Code set definition in N3C Enclave Ingested data Unit harmonization 8/31: 36 Variable code sets ‘version 1.0’ Creatinine in urine is included with blood/serum levels No creatinine from site XXX Mass/volume Mixed with molarity Data element curation A program of NIH’s National Center for Advancing Translational Sciences
  • 26. N3C Data Harmonization Creatinine: units & lab code usage Asthma: code usage across sites Data element curation A program of NIH’s National Center for Advancing Translational Sciences
  • 27. Developing Common MetaVariables Ben Amor Palantir Harold Lehmann Johns Hopkins
  • 28. ● Transparent and collaborative environment where all contributions are acknowledged ● Provenance and reproducibility ● Promptly sharing research results with N3C users ● Publish in high-impact journals ● Attribution for all N3C artifacts N3C Attribution and Publication Principles Researchers, projects, and artifacts are all linked together in the enclave using the Contributor Attribution Model (CAM). N3C Provenance, Transparency, Attribution & Rapid Sharing A program of NIH’s National Center for Advancing Translational Sciences
  • 29. Realizing Team Science A program of NIH’s National Center for Advancing Translational Sciences
  • 30. Key functions can nucleate projects: ● Education & training ● Biostatistics ● Study design ● Evaluation ● Informatics ● Clinical expertise ● Innovation & commercialization ● Community & partnerships N3C Domain Team Expertise: ● Enclave technology ● Data model (OMOP) ● Terminologies ● Data quality ● Codesets, variables, phenotype ● Using/parsing N3C data ● Workflows, methods, algorithms Roles Ingredients (Methods, datasets, instruments) Scientific questions N3C team Science within & across institutions https://covid.cd2h.org/domain-teams CTSAs
  • 31. Diabetes & Obesity Domain Team John Buse Kajsa Kvist Trine Abrahamsen Anna Kakhoska UNC PREMISE: Novel antihyperglycemic medications have associated cardiorenal benefits and reduced mortality in diabetes. QUESTION: How are anti-hyperglycemic medications with established cardiorenal and mortality benefits associated with mortality among patients with type 2 diabetes and COVID-19, compared to commonly used diabetes medications? Carolyn Bramante Steve Johnson Richard Moffitt Tanner Zhang Stephanie Hong Harold Lehmann Davera Gabriel Janos Hajagos
  • 32. A Tsunami of Acute Kidney Injury April 2020 May 2020
  • 33. Kidney Domain Team Sandeep Mallipatu Richard Moffit Stony Brook PREMISE: Kidney Injury contributes importantly to mortality and leads to long term mortality. QUESTIONS: What factors predict kidney injury early? Are there regional differences in AKI incidence? Is AKI incidence in COVID-19 decreasing? What are the predictors of ESKD after AKI? Stephanie Hong https://covid.cd2h.org/kidney/ David H. Ellison J. Brian Byrd Chirag Parikh Farrukh Koraishy Faifan Liu Ivonne Schulman Johns Hopkins
  • 34. N3C Collaborative Analytics Domain Teams Each Domain Team enables researchers with shared clinical questions surrounding COVID-19 to: A program of NIH’s National Center for Advancing Translational Sciences
  • 35. Examples of Collaborative Analytical Domain Teams Clinical topic Analytical questions AKI/ARB/ACE How to predict which patients will develop AKI? Relationship between AKI, invasive ventilation, and mortality. How to predict when AKI will progress to CKD? How do outcomes correlate with dialysis timing? Oxygenation? ACEI vs. ARBs vs. ARNI differentiation? Critical Care How to best prioritize limited resources? What predictors help define which patients will fare best with any given intervention? Diabetes What is the association between HbA1c at baseline and COVID outcomes for patients with diabetes? Are outcomes equivalent among patients with type 2 diabetes and COVID-19 using different anti-hyperglycemic medications? Relationship between COVID correlated diabetes development/exacerbation and outcome and treatment response. Imaging Integrative analysis of image and clinical data to predict outcome and treatment response. Immunosuppressed/ compromised How effective is convalescent plasma? What are the predictors of effectiveness? Oncology What germ line mutations predispose cancer patients to severe COVID outcomes? Pediatrics What endophenotypes exist for MIS-C patients? What are the consequences of childhood COVID infection? Can we build a classifier to predict MIS-C? Pregnancy Determine birth outcomes across COVID-19 severity, intervention, and vaginal versus c-section deliveries; postpartum morbidity and complications in positive cases. Social Determinants of Health (SDoH) Is there a racial disparity to access in testing? What is the transmission intensity among populations by race/ethnicity, rural/urban, income, etc? Are there differences in therapy response? Short/long term Complications Assess longer term conditions, complications, and health care utilization; do these patients have readmissions? What are their outcomes? Hypercoagulability Are there subsets of patients with COVID-19 that are are likely to develop hypercoagulability? Risk factors for hypercoagulability? Does therapeutic enoxaparin or LMWH improve overall outcomes in patients with COVID-19? A program of NIH’s National Center for Advancing Translational Sciences
  • 36. Domain Team - SDoH Example Social Determinants of Health (SDoH) are: “The circumstances in which people are born, grow up, live, work and age, and the systems put in place to deal with illness. These circumstances are in turn shaped by a wider set of forces: economics, social policies, and politics.” -- World Health Organization A program of NIH’s National Center for Advancing Translational Sciences
  • 37. SDoH Domain Team Activities A program of NIH’s National Center for Advancing Translational Sciences
  • 38. SDoH Domain Team Current Research Areas A program of NIH’s National Center for Advancing Translational Sciences
  • 39. Domain Teams & Common Resources To join Domain Teams & access N3C resources: https://covid.cd2h.org/enclave A program of NIH’s National Center for Advancing Translational Sciences
  • 40. Approved Enclave Projects https://covid.cd2h.org/projects View the list of N3C Data Enclave Projects that have been approved by the Data Access Committee (DAC). A program of NIH’s National Center for Advancing Translational Sciences
  • 41. N3C Data Access: Process Data Use Request HSP / Security Training Data Use Agreement https://ncats.nih.gov/n3c/about/applying-for-access A program of NIH’s National Center for Advancing Translational Sciences
  • 42. N3C Registration/Training https://covid.cd2h.org/tutorials Training Office Hours: Tuesdays & Thursdays at 10-11 am PT/1-2 pm ET Registration Required at this link Orientation Video Coming Soon Additional Training Tutorials available in the Enclave Registration for Documents, Meetings & the N3C Data Enclave Requires Authentication Enclave Checklist A program of NIH’s National Center for Advancing Translational Sciences
  • 43. Associationbetween GLP1 receptor agonist (GLP1-RA) and sodium glucose co-transporter 2 inhibitor (SGLT2i) use and COVID-19 outcomes: A nationalretrospectivecohort study Simulationof existingFDA- approved active compoundsagainst COVID protein primary and sub-structures to interrupt protein activityfollowedby epidemiological, in-vitro and in-vivo validation Antibody response to SARS-CoV-2 in people with multiplesclerosis treated with B cell depleting therapies Alcohol Use and Respiratory Outcomes in COVID19 Infections Smoking and COVID-19 Outcomesin U.S. Adults (SCOTUS) Validatea Machine Learning Model to Predict Decompensationin Patients with COVID-19 Workflow Constructionwith SyntheticData -Version 1 Understandingnon-invasiveventilationtreatment failuresin COVID-19 N3C Cohort Characterization COVID-19 in individualswith Down's Syndrome ExaminingAssociationsbetween VitaminD Status and COVID-19 Test Results Identificationof Novel COVID-19 SubphenotypesUsing Temperature Trajectories Identificationof Novel COVID-19 SubphenotypesUsing Temperature Trajectories An evaluation of Direct Acting Anticoagulantsand Dexamethasonein Patientswith COVID-19 Infections N3C Diabetes and Obesity Domain Team level 2 request for data [N3C Operational] Data Ingestionand Harmonization Studying COVID-19 Remission,Recrudescence, Recurrence, and Reinfection [N3C Operational] Implementationof Syntegra SyntheticData Generator” Impact of medicationon outcomesfor diabeticpatients Monocytopeniain COVID-19 Acute Kidney Injury in Pediatric COVID-19 Patients Using MachineLearning to differentiateCOVID-19 infectionwith seasonalflu COVID-19 and Percutaneous CatheterizationInterventions: ModelingRisk of Serious Adverse Outcomes COVID-19 infectionand mortalityamong individualswith disabilities Deep learning of longitudinalchest X-ray and clinical variablesto predict needs for invasive mechanical ventilationand mortalityin COVID-19 patients Continued In-HospitalACEi and ARB Use in HypertensiveCOVID-19 Patients AI-AssistedAssessment,Tracking, and Reporting of COVID-19 Severity on Chest CT Impact of COVID-19 infectionin patientswith pulmonary non-tuberculousMycobacterium (NTM) infection: A cohort study. Disparitiesin COVID-19 [N3C Operational] CollaborativeAnalytics BenchmarkingGenerative Adversarial Network (GAN) based synthetic EHR data generation methodsfor enabling COVID-19 research Outcomes of Acute Pulmonary Embolismin COVID-19 [N3C Operational] SyntheticData ValidationUse Cases N3C Pregnancy Task Team: COVID-19 Incidence, Treatment, and Outcomes in Pregnant Women Contributionof Race and other Social Determinantsof Health to Disparitiesin Patient Outcomes in COVID-19 HospitalizationRates Feb-April vs May-October The Effect of COVID-19 Stay-At-Home Orders on HemoglobinA1c Levels in DiabeticPatients DevelopingDynamic Graphs for Predictionand Classificationof COVID-19 Patient Trajectories Occurrence of neurologicaldiseases in hospitalizedpatientswith COVID-19 infection COVID-19 and Air pollution Towards the development of a learning health systemin the COVID-19 pandemic:analysis of patient data to assist clinicaldecisionmaking ProtectiveEffects of MedicationsAgainst SARS-CoV-2 Infectionin Patientswith ExistingPrescriptions Associationbetween glucagon-likepeptide 1 receptor agonist (GLP1-RA) and sodium glucose co-transporter 2 inhibitor (SGLT2i) use and COVID-19 outcomes: A national retrospectivecohort study MultiorganDysfunctionSyndrome and Complex Clinical Trajectory Data-driven Investigationof Health Disparitiesin COVID-19 Outcomes: A Focus on Behavioral Health Investigatingthe impact of biases on the performance of analytical models for COVID-19 related care. Factors affectingrisk of poor outcomes for COVID-19 for patientswith diabetes COVID-19 as a HeterogeneousProcess: Varying Underlying PathophysiologicalMechanismsat Different Time Points and Severities Orthopaedic Surgery in the National COVID Cohort Collaborative(N3C) Modelingof COVID-19 Risks for Back-to-Work Programs COVID-19 impact on pregnancy and fetal wellbeing Treatment associatedwith lower mortalityin hospitalizedCOVID-19 patients Stage Aware Prediction of COVID19 Disease Progression Stroke and COVID Population: An N3C and UVA OMOP analysis Associationof Dupilumab with Protection from COVID-19 Respiratory Failure CardiovascularComplicationsof COVID-19 Examiningthe dynamicsin social determinantsof health with regards to differential COVID-19 incidenceacross the United States Use, Safety and Effectivenessof Therapies to Treat COVID-19 NIRVANA Developingan applicationto predict the severity of COVID-19 infectionsof individual patientsby applyingartificial intelligencemethodologies Developingan applicationto predict the severity of COVID-19 infectionsof individual patientsby applyingartificial intelligencemethodologies N3C ImmunoSuppressed/CompromisedTask Team: The Impact of COVID-19 on the ISC Population Epidemiologyof Acute and Chronic Kidney Injury Associated SARS-CoV-2 Infection Analysisof Time Windows as Determining Factors for COVID-19 Patient Outcomes AssessingTemporal Lab Value Changes and Medicationsas Predictors of Health Outcomes for COVID19+ Patients [N3C Operational] Phenotype and Data AcquisitionTeam Operations Retrospective identificationof medicationsto treat COVID-19 Adaptive and interpretablemachine learning to predict COVID-19 trajectory and severity Case-Control Studies of Medicationsand Their Possible Associationswith COVID-19 Severity HIV and COVID-19: Effect of Shelter-In-PlaceOrders on Virologic Suppression Impactsof COVID -19 in Older Adults (Elder Impact Domain) Level 2 Impactsof COVID -19 in Older Adults (Elder Impact Domain) Differential Clinical Outcomesfor Drug Repurposing Candidates Discovered in BSL3 SARS-CoV-2 InfectionModel Study Phenotype of COVID-19 in Patients with Hemophilia: A NationalCohort Study Neurological Manifestationof SARS-CoV-2 infection in African Americans: AI-based Novel Approach of Prognostic and Risk Stratification Models Numerous Projects Numerous People Numerous Institutions Expertise & Resources Connected 91 Projects 1231 People 313 Institutions A program of NIH’s National Center for Advancing Translational Sciences
  • 44. ● N3C comprises the largest, most representative patient-level COVID-19 cohort in the US and continues to grow ● We CAN do transparent, reproducible, innovative science (including ML) on sensitive observational data at scale, together! ● N3C is an innovative partnership between clinical sites, CDM communities, NIH ICs, CD2H, and commercial partners ● Automation of data extraction and minimum requirements reduces burden and increases site participation ● Robust attribution of all contributors; also provides great venue for trainees ● N3C data is complicated, but there are many people and resources to help users do good science Step 4. Federated Analytics with HPC Takeaways A program of NIH’s National Center for Advancing Translational Sciences
  • 45. Register with N3C: https://labs.cd2h.org/registration/ Joining Workstreams: N3C Data Ingestion & Harmonization Workstream Slack Channel Harmonization Google Group Harmonization N3C Phenotype & Data Acquisition Workstream Slack Channel Phenotype Google Group Phenotype N3C Collaborative Analytics Workstream Slack Channel Analytics Google Group Analytics N3C Data Partnership & Governance Workstream Slack Channel Governance Google Group Governance N3C Synthetic Clinical Data Workstream Slack Channel Synthetic Google Group Synthetic N3C Implementation Workstream- Coming soon Additional Information: Onboarding N3C, Slack, Google | Finding and Joining a Google Group NCATS N3C Webpage N3C Website How to Get Involved with N3C A program of NIH’s National Center for Advancing Translational Sciences
  • 46. COVID-19 Research Open House Week January 19th-25th Kick-off Event: Community Research Symposium Tuesday January 19, 2021 | 9-10am PT/12-1pm ET ● Opening remarks from N3C leadership ● PI/Clinician Testimonial: David Ellison, MD ● Demonstration of the N3C Data Enclave ● Flash talks from the Pregnancy & Diabetes/Obesity Domain Teams ● N3C Tutorial: How to Get Involved Participating Meeting Schedule: More Details: https://covid.cd2h.org/n3c-openhouse A program of NIH’s National Center for Advancing Translational Sciences
  • 47. Melissa A. Haendel,1,4,7,8,10,13,14,52,78,101 Christopher G. Chute,1,4,8,10,13,14,52,78,100,101 Tellen D. Bennett,9,10,13,14,52,100,101 David A. Eichmann,4,9,10,13,78,101 Justin Guinney,4,9,10,14,78,101 Warren A. Kibbe,9,10,52,78,101 Philip R.O. Payne,4,9,10,78,101 Emily R. Pfaff,9,10,13,15,52,78 Peter N. Robinson,4,9,10,15,52,78,100 Joel H. Saltz,10,13,14,15,52,78,101 Heidi Spratt,9,10,100 Christine Suver,10,78,101 John Wilbanks,10,78,101 Adam B. Wilcox,10,101 Andrew E. Williams,10,13,78 Chunlei Wu,9,13,14,78 Clair Blacketer,15,52 Robert L. Bradford,9,52 James J. Cimino,10,14,101 Marshall Clark,9,15,52 Evan W. Colmenares,9,15,52 Patricia A. Francis,78 Davera Gabriel,9,10,13,14,15,52 Alexis Graves,7,9,78 Raju Hemadri,9,15,52 Stephanie S. Hong,9,15,52 George Hripscak,10,52 Dazhi Jiao,9,15,52 Jeffrey G. Klann,14,52,101 Kristin Kostka,9,15,52 Adam M. Lee,9,15,52 Harold P. Lehmann,9,15,52 Lora Lingrey,9,15,52 Robert T. Miller,9,15,52 Michele Morris,9,15,52 Shawn N. Murphy,9,15,52 Karthik Natarajan,9,15,52 Matvey B. Palchuk,9,15,52 Usman Sheikh,9,78 Harold Solbrig,9,15,52 Shyam Visweswaran,10,15,52,101 Anita Walden,7,10,13,14,52,101 Kellie M. Walters,10,14,101 Griffin M. Weber,10,101 Xiaohan Tanner Zhang,9,15,52 Richard L. Zhu,9,15,52 Benjamin Amor,78 Andrew T. Girvin,15,78 Amin Manna,78 Nabeel Qureshi,15,78 Michael G. Kurilla,10,78 Sam G. Michael,10,78 Lili M. Portilla,101 Joni L. Rutter,1,101 Christopher P. Austin,101 Ken R. Gersing,78,101 Shaymaa Al-Shukri,4,15 Adil Alaoui,101 Ahmad Baghal,15 Pamela D. Banning,15,100 Edward M. Barbour,8,15 Michael J. Becich,15,52,101 Afshin Beheshti,14 Gordon R. Bernard,8,15 Sharmodeep Bhattacharyya,100 Mark M. Bissell,9,15 L. Ebony Boulware,14,100 Samuel Bozzette,100,101 Donald E. Brown,101 John B. Buse,14 Brian J. Bush,8,101 Tiffany J. Callahan,14,52 Thomas R. Campion,8,15 Elena Casiraghi,9,15 Ammar A. Chaudhry,13,14 Guanhua Chen,9 Anjun Chen,13 Gari D. Clifford,8,15 Megan P. Coffee,14,100 Tom Conlin,14 Connor Cook,7,78 Keith A. Crandall,9,14,101 Mariam Deacy,78 Racquel R. Dietz,78 Nicholas J. Dobbins,8,9 Peter L. Elkin,15,52,100 Peter J. Embi,52,101 Julio C. Facelli,8,15 Karamarie Fecho,13 Xue Feng,9 Randi E. Foraker,8,13,15 Tamas S. Gal,8,15 Linqiang Ge,14 George Golovko,15,101 Ramkiran Gouripeddi,14,15 Casey S. Greene,13,14 Sangeeta Gupta,52,101 Ashish Gupta,13,101 Janos G. Hajagos,9,15 David A. Hanauer,15,52 Jeremy Richard Harper,9,14,52 Nomi L. Harris,14 Paul A. Harris,101 Mehadi R. Hassan,9 Yongqun He,15,52,100 Elaine L. Hill,9,14 Maureen E. Hoatlin,14 Kristi L. Holmes,4,101 LaRon Hughes,14 Randeep S. Jawa,14 Guoqian Jiang,14 Xia Jing,7,14 Marcin P. Joachimiak,8,15 Steven G. Johnson,9,14,101 Rishikesan Kamaleswaran,9,15,78 Thomas George Kannampallil,15,101 Andrew S. Kanter,15,52 Ramakanth Kavuluru,9,13,14 Kamil Khanipov,8,14 Hadi Kharrazi,9,14 Dongkyu Kim,15,52 Boyd M. Knosp,8,15 Arunkumar Krishnan,9 Tahsin Kurc,9,15 Albert M. Lai,101 Christophe G. Lambert,52,101 Michael Larionov,14 Stephen B. Lee,1,14 Michael D. Lesh,9 Olivier Lichtarge,14 John Liu,9 Sijia Liu,8,9,101 Hongfang Liu,9,15 Johanna J. Loomba,1,15,78,101 Sandeep K. Mallipattu,9,14,15 Chaitanya K. Mamillapalli,14 Christopher E. Mason,15 Jomol P. Mathew,8,15,52 James C. McClay,101 Julie A. McMurry,1,4,7,9,13,14,78 Paras P. Mehta,14 Ofer Mendelevitch,9 Stephane Meystre,8,14,15 Richard A. Moffitt,9,13,15 Jason H. Moore,8,9 Hiroki Morizono,13,14,15,52 Christopher J. Mungall,15,52 Monica C. Munoz-Torres,7,10,78 Andrew J. Neumann,78 Xia Ning,14 Jennifer E. Nyland,13,14 Lisa O'Keefe,78 Anna O'Malley,78 Shawn T. O'Neil,78 Jihad S. Obeid,10,14,15 Elizabeth L. Ogburn,13 Jimmy Phuong,9,15,52,100,101 Jose D Posada,8,15 Prateek Prasanna,14,52 Fred Prior,9,14,15 Justin Prosser,9,78 Amanda Lienau Purnell,101 Ali Rahnavard,9,52 Harish Ramadas,9,52,78 Justin T. Reese,9,10 Jennifer L. Robinson,14,100 Daniel L. Rubin,101 Cody D. Rutherford,9,101 Eugene M. Sadhu,8,15 Amit Saha,9 Mary Morrison Saltz,15,52,101 Thomas Schaffter,78 Titus KL Schleyer,14 Soko Setoguchi,8,14,15 Nigam H. Shah,8,14 Noha Sharafeldin,14 Evan Sholle,15,52 Jonathan C. Silverstein,15,52,101 Anthony Solomonides,101 Julian Solway,14,101 Jing Su,101 Vignesh Subbian,9,52,101 Hyo Jung Tak,15 Bradley W. Taylor,9,14 Anne E. Thessen,14,101 Jason A. Thomas,15 Umit Topaloglu,15,52 Deepak R. Unni,8,9,15,52 Joshua T. Vogelstein,14 Andréa M. Volz,7 David A. Williams,14,15 Kelli M. Wilson,9,78 Clark B. Xu,8,9,15 Hua Xu,9,10,14 Yao Yan,9,15,52 Elizabeth Zak,8,15 Lanjing Zhang,101 Chengda Zhang,14 Jingyi Zheng,14 1CREDIT_00000001 (Conceptualization)4CREDIT_00000004 (Funding acquisition)7CRO_0000007 (Marketing and Communications)8CREDIT_00000008 (Resources)9CREDIT_00000009 (Software role)10CREDIT_00000010 (Supervision role)13CREDIT_00000013 (Original draft)14CREDIT_00000014 (Review and editing)15CRO_0000015 (Data role)52CRO_0000052 (Standards role)78CRO_0000078 (Infrastructure role)100Clinical Use Cases101Governance https://academic.oup.com/jamia/advance- article/doi/10.1093/jamia/ocaa196/5893482
  • 49. Thank you! Thank you! A program of NIH’s National Center for Advancing Translational Sciences