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

In this report, we characterized two cohorts; one indexing on acute Coronavirus Disease (COVID) diagnosis or positive Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test, and a second cohort indexing on Long COVID. These analyses are intended as an exploration of the FDA's Sentinel Electronic Health Record (EHR) data sources (specifically TriNetX) to capture Long COVID and assess feasibility of future Long COVID studies in TriNetX.

The study period includes data from January 1, 2021 to February 23, 2023 and contains data from 34 health care organizations (HCOs), provided through the TriNetX Live™ platform in their USA with No Shift Network. The query was run on March 29, 2023.

Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE.

This analysis supports the U.S. Food and Drug Administration (FDA)'s participation in the European Medicines Agency (EMA)-funded project, CONSIGN (COVID-19 infectiOn aNd medicineS In preGNancy)1 , to understand the natural history of COVID-19 in pregnant patients.

In this request, we evaluated the prevalence of medication use among pregnant patients with and without COVID-19 and non-pregnant patients with COVID-19 and described maternal at-risk conditions and the severity of COVID-19 in the Rapid COVID-19 Sentinel Distributed Database (SDD).

The study period includes data from January 1, 2020 to May 31, 2021. We distributed this request to six Sentinel Data Partners on September 17, 2021.

• 1CONSIGN study: COVID-19 infection and medicines in pregnancy- a multinational registry based study. European Network of Centres for Pharmacoepidemiology & Pharmacovigilance. Accessed June 1, 2022. https://catalogues.ema.europa.eu/node/3303/administrative-details

Automated phenotyping algorithms can reduce development time and operator dependence compared to manually developed algorithms. One such approach, PheNorm, has performed well for identifying chronic health conditions, but its performance for acute conditions is largely unknown. In this study, we implement and evaluate PheNorm applied to symptomatic COVID-19 disease to investigate its potential feasibility for rapid phenotyping of acute health conditions.

Sequential surveillance of therapeutics in electronic health data enables routine monitoring for a statistically significant increased risk of specific adverse events. When performing sequential surveillance of drug safety, a formal study is designed and repeated as data accrues to identify any increased risk for outcomes of interest as quickly as possible. This monitoring is continued until 1) there are findings that indicate that a safety issue may be present and therefore more follow-up or a regulatory action is warranted, or 2) until findings provide assurance that the safety issue of interest does not require further action.

The Sentinel System has integrated the capability to perform sequential surveillance into its routine analytic tools. The tools have the ability to perform multiple executions of cohort or self-controlled risk interval analyses. This project aims to leverage these capabilities to assist FDA in their response to the COVID-19 pandemic – specifically monitoring safety of new therapeutics. A master protocol will be designed such that it can be leveraged to proactively monitor the safety of these therapeutics as they undergo FDA review and are introduced to the market. 

The goal of this analysis was to describe COVID-19 therapeutic treatment and death among patients who were hospitalized with COVID-19 and among patients with severe COVID-19, stratified by racial and ethnic group in the TriNetX platform. In addition to describing these groups overall, we also described the subset of each group with evidence of vaccination against COVID-19. 

This analysis contains four reports: 

• Report 1: The study period includes data from January 1, 2021 to April 30, 2021 and contains data from 36 health care organizations (HCOs), provided through the TriNetX Live™ platform in their USA Network. The query was run on June 21, 2022.
• Report 2: The study period includes data from May 1, 2021 to August 31, 2021 and contains data from 36 HCOs, provided through the TriNetX Live™ platform in their USA Network. The query was run on June 13, 2022.
• Report 3: The study period includes data from September 1, 2021 to December 31, 2021 and contains data from 36 HCOs, provided through the TriNetX Live™ platform in their USA Network. The query was run on June 30, 2022.
• Report 4: The study period includes data from January 1, 2022 to April 30, 2022 and contains data from 36 HCOs, provided through the TriNetX Live™ platform in their USA Network. The query was run on July 12, 2022.

This analysis investigates risk of COVID-19-related hospitalization and severe COVID-19 (COVID-19-related hospitalization requiring intubation, mechanical ventilation or intensive care unit [ICU] admission; or inpatient death during a COVID-19 hospitalization) among a population of proton pump inhibitor (PPI) new users with gastroesophageal reflux disease (GERD) compared to a population of famotidine new users with GERD. 

The study period includes data from April 1, 2020 to October 1, 2020. We distributed this request to five Sentinel Data Partners on June 1, 2023.

The analytic package associated with this analysis can be found externally in Sentinel's Git Repository located here. The Git Repository serves as Sentinel's version control tracking system for analytic packages and technical documentation. 

This poster describes treatments for hospitalized and critical COVID-19 patients by race and ethnicity from January 2021 through April 2022. It was presented at the 39th International Conference on Pharmacoepidemiology and Therapeutic Risk Management. 

In this poster, data from a large US hospital network was used to examine daily dexamethasone doses in hospitalizations with COVID-19. It was presented at the 39th International Conference on Pharmacoepidemiology and Therapeutic Risk Management. 

Systemic factors predispose United States (US) racial minority groups to a greater risk of severe COVID-19 outcomes. This poster determines the association between race and COVID-19 outcomes adjusted for baseline demographic, clinical, and socioeconomic characteristics. It was presented at the 39th International Conference on Pharmacoepidemiology and Therapeutic Risk Management.