N3C Public Health Answers to Speed Tractable Results (PHASTR)

The following questions are open for application:

Does metformin show a reduction of severe outcomes of COVID-19 or of Long COVID in the N3C Data Enclave

A recent clinical trial (COVID-OUT) demonstrated that metformin lowered the odds of emergency department visits, hospitalizations, or death by over 40% and also decreased the incidence of long COVID as diagnosed by a medical provider.  The fundamental question being asked is:  Does metformin reduce the incidence of severe outcomes of COVID-19 and/or prevent Long COVID?



Application Deadline: Aug 31, 2023
Contract Amount: $50,000.00

Does molnupiravir show a reduction of severe outcomes of COVID-19 in the N3C Data Enclave

Molnupiravir has demonstrated variable effects on the risk of hospitalization or mortality among outpatients with COVID-19.  Prior results from the randomized, placebo-controlled MOVe-OUT trial demonstrated a statistically significant reduction in the risk of all-cause hospitalization or death in unvaccinated patients at increased risk, while a more recent randomized open-label study (PANORAMIC) in a high-risk vaccinated population disclosed no impact on all-cause hospitalization or death (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02597-1/fulltext).  The question to be addressed is: Does molnupiravir reduce the risk of hospitalization or death within one month of COVID-19 in at-risk patients with COVID-19 in the N3C population, controlling for confounding variables such as vaccination, risk factors for severe outcomes, concomitant therapy, and variant epoch.

Application Deadline: Aug 31, 2023
Contract Amount: $50,000.00

Is Long COVID associated with an increased risk of mortality?

Long COVID (post-acute sequelae of COVID-19) has been associated with a variety of clinical manifestations that may produce lasting morbidity, but the impact of Long COVID on mortality risk remains unclear. A recent descriptive study of death certificate data in the US National Vital Statistics System (https://stacks.cdc.gov/view/cdc/121968) has disclosed cases in which long COVID terms appeared in death certificates, indicating Long COVID as an underlying or contributing cause of death. The fundamental question being asked is: Is Long COVID associated with an increased risk of mortality relative to patients who experience acute COVID-19 not followed by Long COVID, and a population of uninfected individuals.

Application Deadline: Feb 15, 2023
Contract Amount: $50,000.00

Use of the N3C enclave and machine learning to create generalizable algorithms that predict patient outcomes at (a) diagnosis, and (b) time of hospitalization

Over the last three years, many studies have sought to identify risk factors for more severe SARS-CoV-2 infection and adverse outcomes of COVID-19. Since the onset of the pandemic, progressive insights have been gained into demographic and clinical features, co-morbidities, various biomarkers, therapeutic strategies, and social factors that affect acute disease outcomes among outpatients and inpatients. The fundamental question being asked is: Based on knowledge concerning prognostic factors that has accrued since 2019, can the N3C enclave be leveraged to identify generalizable algorithms that predict hospitalization, disease severity, and mortality associated with SARS-CoV-2 infection?

Application Deadline: Feb 15, 2023
Contract Amount: $50,000.00

Does the use of UDCA (ursodeoxycholic acid) at baseline reduce the incidence and/or severity of COVID-19?

Recently published preclinical data (link below) suggest ursodeoxycholic acid (UDCA) may inhibit SARS-CoV-2 infection through downregulation of expression of the ACE2 receptor.  Although this agent is used in clinical practice for other indications, it has not been evaluated in clinical trials to assess its impact on SARS-CoV-2 infection. The fundamental question being asked is: Does UDCA use at baseline reduce the incidence and/or severity of COVID-19?


Application Deadline: Feb 15, 2023
Contract Amount: $50,000.00

SARS-CoV-2 Reinfection Severity

Does reinfection with SARS-CoV-2 compared to first infection produce clinical illness that is more severe, the same as, or less severe compared to initial SARS-CoV-2 infection?  


Application Deadline: Nov 25, 2022
Contract Amount: $50,000.00

Neurologic sequelae COVID

What is the spectrum of neurologic sequelae at 12 months following infection in survivors of acute COVID, compared to individuals who have not had COVID?


Application Deadline: Nov 25, 2022
Contract Amount: $50,000.00



The N3C PHASTR is designed to quickly address high-impact questions that can be answered with N3C data. These questions will be identified by NCATS and NIH leadership, and proposals to address them within the N3C Data Enclave will be open for a short time for each. Successful proposals will be awarded a short-term contract and will be expected to produce quantitative answers within a given time frame.

Following standard N3C policy, source data cannot be duplicated outside of the N3C Data Enclave, and all analyses must be completed within the Enclave. Results will be submitted by investigators via the N3C Results Download process; this process and other policies are described under Governance Resources.

Training materials and information on office hours and other support are available. For questions about the initiative, please contact publichealth@nih.gov. For other inquiries about N3C, email cd2h@cuanschutz.edu.


NCATS launched N3C PHASTR to address high-impact questions that are not being investigated by the research community. The effort also is funded by the NIH National Institute of General Medical Sciences.


Provide fast, actionable analysis of high-impact, public health research questions. Engage the community capable of working with N3C “big data” to answer public health-related research questions of interest.

Support Mechanism

The N3C Public Health Answers to Speed Tractable Results, or PHASTR, works through a subcontract mechanism. Proposals to address questions will be submitted to NCATS’ primary contractor, Axle Informatics, from the N3C platform. Teams with successful proposals will work through Axle (as a subcontractor) to complete the work.

For more information, watch the  N3C PHASTR Q&A Webinar (11/17/22)

Who Can and Cannot Apply

Any individual or team with appropriate expertise, experience, and resources can submit a proposal, provided there is no real or apparent conflict of interest.

All offerors must follow all registration and data access processes associated with the environment, including meeting the access requirements for Level 3 data as described.

Submission Process


All work will be performed utilizing the N3C Data Enclave.

Offerors – those wishing to submit a proposal in response to a N3C PHASTR public health-related research question – will access the proposal submission process from the N3C home page where they can find a new button labeled "Public Health Proposal."

The N3C PHASTR submission package consists of the following components that offerors must include in their proposals:

  • Project Summary: A high-level description of how the overall question and associated Aims will be addressed. Include primary and major secondary objectives and how they align with the stated Aims. Briefly describe the overall design of the study and effort (e.g., retrospective case-control study; uncontrolled characterization of COVID-19 outcomes; development of a supervised learning algorithm for prediction of outcome X; development of a clustering algorithm to identify subphenotypes of condition Y). 
  • Strategy for Cohort Identification: The proposed approach to data set/cohort creation for analysis. This includes an outline of key criteria for inclusion in the analysis, anticipated sample size; and, if applicable, a definition of exposures of interest. If controls are used, the manner in which these are identified should be specified. Referring to the Inclusion, Exclusion, and Phenotype sections of the PHASTR posting is appropriate.
  • Analytics Approach: A proposed methodology for answering the question. This should include a brief description of endpoints, statistical methodology, key covariates, any critical statistical assumptions and limitations, the approach to missing data, and plans to mitigate bias. Referring to elements of the PHASTR posting is appropriate. A brief outline of anticipated sources of bias, potential confounding, and missing data is required, along with a plan for how they will be addressed.
  • Justification: A description of how the proposed strategy will address the overall question(s).

Proposal Evaluation

The N3C PHASTR proposals will be evaluated by the NCATS contractor’s scientific staff using the information provided in the Proposal Preparation Instructions. All offerors will be sent an email to convey the results of the evaluation.

Successful offerors will be offered a subcontract by the NCATS contractor to complete the work.

Contact Information

For questions about the initiative, please contact publichealth@nih.gov. For other inquiries about N3C, email cd2h@cuanschutz.edu.

Quick Start for Experienced N3C Users

If you are already familiar with N3C, here’s what you need to know:

  • Proposals are modified Data Use Requests, accessible from the Enclave Homepage under "Public Health Proposals."
  • All offerors must be from a Data Use Agreement-holding institution.
  • The Level 3 Limited Data Set will be available.
  • Results will be submitted through the N3C results download process; proposals will describe the expected result formats.
  • Results will be visualized on the N3C public health dashboard.
  • Your project workspace will have read-only access to all other project workspaces involved with this initiative for code and data re-use. After the contract is completed, if you wish to continue the work for publication or other noncontract uses, you will need to upgrade the Data Use Request to a research Level 3 and submit IRB letters of determination. N3C staff will support this process if desired.


Public health questions come from a variety of sources, including investigators, NIH staff, policy, and regulatory agencies.

Number of subcontracts for each question will differ and can be found in the Application Information Section.

The amount varies depending on the complexity of other work needed. The amount can be found in the Application Information Section.

This varies with each question and only starts after the contract has been finalized with the institution. The time can be found in the Application Information Section Clock.

Each question will have a detailed description of what is expected. NCATS' goal is to make the results of the information broadly available, and NCATS will post them on the N3C public health dashboard. This includes a short description of the results as well as any tabular output needed for visualization of the information.

All subcontractor proposals are reviewed by a federal prime contractor, Axle Informatics; an information contractor; and their scientific specialist.

Each public health question contains information on what is being asked, including:

  • Application Information: Details on the application process
  • Contract Description: Work order parameters

For inquiries about the initiative, please contact publichealth@nih.gov. For other inquiries about N3C, email cd2h@cuanschutz.edu.

The contract mechanism was chosen because expectations and deliverables are clearly defined.

Yes all analyses must be done within the N3C Data Enclave.