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?
https://www.nejm.org/doi/full/10.1056/NEJMoa2201662
https://www.medrxiv.org/content/10.1101/2022.12.21.22283753v1
Application Deadline: Aug 31, 2023
Contract Amount: 50000
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: 50000
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: 50000
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: 50000
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?
https://www.nature.com/articles/s41586-022-05594-0
Application Deadline: Feb 15, 2023
Contract Amount: 50000
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?
https://www.researchsquare.com/article/rs-1749502/v1
Application Deadline: Nov 25, 2022
Contract Amount: 50000
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?
https://www.nature.com/articles/s41591-022-02001-z
Application Deadline: Nov 25, 2022
Contract Amount: 50000
About PHASTR
Background
The N3C PHASTR initiative was designed to quickly address high-impact questions that can be answered with N3C data. These questions were identified by NCATS and NIH leadership. Successful proposals were awarded a short-term contract.
Goals
Provided fast, actionable analysis of high-impact, public health research questions. Engaged the community capable of working with N3C “big data” to answer public health-related research questions of interest. Successful offerors were offered a subcontract by the NCATS contractor to complete the work
For more information, watch the N3C PHASTR Q&A Webinar (11/17/22).
Contact Information
For questions about the initiative, please contact hythem.sidky@nih.gov. For other inquiries about N3C, email ncats_n3c@nih.gov.
NCATS launched the N3C PHASTR initiative to tackle high-impact research questions that were not being addressed by the broader scientific community. This effort was also supported by funding from the NIH National Institute of General Medical Sciences.
The following questions were proposed for applicants:
Submission Process
Application
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 hythem.sidky@nih.gov. For other inquiries about N3C, email ncats_n3c@nih.gov.
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.
FAQs
Public health questions came from a variety of sources, including investigators, NIH staff, policy, and regulatory agencies.
This varied with each question and started after the contract had been finalized with the institution. The time can be found in the Application Information Section Clock.
Each question had a detailed description of what was expected. NCATS' goal was to make the results of the information broadly available, and NCATS posted them on the N3C public health dashboard. This included a short description of the results as well as any tabular output needed for visualization of the information.
All subcontractor proposals were reviewed by a federal prime contractor, Axle Informatics; an information contractor; and their scientific specialist.
For inquiries about the initiative, please contact hythem.sidky@nih.gov. For other inquiries about N3C, email ncats_n3c@nih.gov.
The contract mechanism was chosen because expectations and deliverables are clearly defined.
Yes, all analyses were within the N3C Data Enclave.
To Cite the N3C: "The analyses described in this [publication/report/presentation] were conducted with data or tools accessed through the NCATS N3C Data Enclave https://covid.cd2h.org and N3C Attribution & Publication Policy v 1.2-2020-08-25b supported by NCATS Contract No. 75N95023D00001 and [insert additional funding agencies or sources and reference numbers as declared by the contributors in their form response above]. This research was possible because of the patients whose information is included within the data and the organizations (https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the on-going development of this community resource [https://doi.org/10.1093/jamia/ocaa196]."
For publication submission information, please see the Publication Review Page