FDA Sentinel System's Coronavirus (COVID-19) Activities

Among hospitalized non-pregnant adults with COVID-19, we aimed to describe the number of patients with hospitalized thrombotic events or death through 28 days. We stratified each outcome by d-dimer level and record of early intensive care services. We used electronic health record (EHR) data from the TriNetX Live™ USA Network to identify adults with positive COVID-19 antigen or PCR laboratory test results or documented COVID-19 diagnoses within ±3 days of a hospitalization record. We queried 65 health care organizations’ data from February 20, 2020 through October 16, 2020.

To inform future sample size calculations pertaining to thrombosis in COVID-19-associated coagulopathy, we describe occurrence of thrombotic events and death among patients aged 40-79 years not hospitalized at the time of COVID-19 identification. We used electronic health record (EHR) data from 64 health care organizations (including inpatient and outpatient data), provided through the TriNetX Live™ platform in their USA network to identify COVID-19 cases in the outpatient setting from February 20, 2020 through September 11, 2020. 

The COVID-19 Natural History Master Protocol effort involves the development of a protocol designed to identify multiple COVID-19 cohorts to support a variety of on-demand queries and subsequent inferential studies. The protocol will be adaptable to various data sources with clinically rich data and will include specific populations of interest, such as the pediatric population, pregnant women, and other vulnerable populations identified by FDA. The implementation of the Natural History protocol will prioritize data source capabilities, such as: a) the capacity to form stable population-based cohorts that can be refreshed quickly and reliably over time, b) deep on-site pharmacoepidemiology experience with a research record of both descriptive and inferential studies, and c) demonstrated analytic capability to support rapid on-demand queries which support identification of the natural history of COVID-19. Expert infectious disease specialists and pharmacoepidemiologists will lead development of this protocol and its implementation in various data sources in the Sentinel network.

This project supports FDA’s COVID-19 response through: 

1. Adding COVID-19 laboratory results data to the Sentinel Common Data Model (SCDM) for routine querying in the Active Risk Identification and Analysis (ARIA) system
2. Developing access to the “freshest feasible” rapid COVID-19 data from Sentinel data partners in the distributed data network 

This activity encompasses two aims that are using inpatient electronic health record data from HCA Healthcare:

Aim 1: The objective for Aim 1 is to describe the natural history of disease among hospitalized COVID-19 patients as identified based on diagnosis codes and/or laboratory results. This project will describe patients’ clinical characteristics, healthcare utilization, disease progression, and outcomes. Queries will be updated periodically to understand trends in the disease course and patient care over time.
 

Aim 2: The objective for Aim 2 is to establish the capacity to monitor critical drugs used in the care of hospitalized COVID-19 patients, and to sequentially monitor utilization through repeated data updates.
 

These projects build on the work conducted for the FDA’s Office of Counterterrorism and Emerging Threats (OCET) in understanding how the Sentinel System may be useful to study the safety and effectiveness of medical countermeasures.

The purpose of this project is to design and implement a system that enables rapid querying of electronic health record (EHR) data to support FDA's COVID-19 response. The project will partner with TriNetX to provide access to the TriNetX querying platform and TriNetX Live™ data network. More than 80% of the 76 U.S. Health Care Organizations (HCO) in the TriNetX Live™ data network refresh their data in one, two, or four-week intervals.

This activity supports investigators of COVID-19 related drug trials that need a digital platform for patient informed consent when face to face contact is not possible or practical. The COVID MyStudies application allows for secure and remote electronic consent. The end product is a signed consent form emailed to the patient or legally authorized representative and a copy which the investigator can access in a secure and compliant manner through the platform. The investigator can print the form or transfer an electronic copy into another electronic system. Under the FDA-Catalyst program, the Sentinel Operations Center will coordinate the branding and administration of this application. 

Funding for use of this system by Investigators, Healthcare delivery systems, and Sponsors is provided by the FDA. COVID MyStudies is currently available in the Apple App and Google Play Stores. Investigators, Healthcare delivery systems, and Sponsors can contact CDERMedicalPolicy-RealWorldEvidence@fda.hhs.gov to get started.

More information about COVID MyStudies can be found here.

The following three projects support the FDA’s Office of Counterterrorism and Emerging Threats (OCET) in understanding how the Sentinel System may be useful to study medical countermeasure (MCM) safety and effectiveness and to provide a valuable baseline for comparison during a public health emergency. We will evaluate the capture of ordinal endpoints and treatment information using influenza as a use case. In March 2020, as noted below under Activity 3, the focus was extended to COVID-19. 

Activity 1: This descriptive analysis will query the Sentinel Distributed Database to determine the feasibility of capturing meaningful ordinal endpoints for a subset of patients, using an influenza scenario to serve as a proxy for public health emergency events. This activity will describe individuals with influenza-like illness (ILI), pneumonia and influenza, and medically attended acute respiratory illness during three prior influenza seasons. For the ILI cohorts, treatment with an influenza antiviral in the outpatient setting will also be assessed.

Activity 2: The objective of this methods activity is to determine whether there is evidence of residual confounding in the association between influenza antiviral(s) and influenza complications in observational studies. First, we will compare study results to estimates derived from randomized controlled clinical trials, with the goal of replicating the known association shown in clinical trials. Second, the SOC will conduct analyses using a negative control period as well as a negative control endpoint to evaluate its analysis model.

Activity 3: This descriptive analysis is similar to Activity 1 but will be set solely in the inpatient setting using electronic health record (EHR) data. The project will assess baseline characteristics, treatment, and endpoints among patients hospitalized with ILI. In March 2020, FDA requested that COVID-19 cohorts be added to the activity. 

Activity 1 and 3 ordinal endpoints include hospitalization, intensive care unit stay, mechanical ventilation, ECMO, and in-hospital death. 
Activity 2 outcomes include all-cause hospitalization, hospitalized pneumonia, respiratory antibiotic use; the negative control is non-vertebral fractures.