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

In this report, we identified new and prevalent users of proton pump inhibitors (PPIs), single-agent H2 receptor antagonists (H2RAs), and famotidine who had a diagnosis of gastroesophageal reflux disease (GERD) in the Rapid Sentinel Distributed Database (SDD). We also estimated the incidence of COVID-19 and COVID-19-related adverse outcomes among these individuals.

The study period includes data from April 1, 2020 to December 15, 2020. We distributed this request to seven Sentinel Data Partners (DPs) on June 3, 2022.

While potential harm from high doses of systemic dexamethasone for clinical management of COVID-19 is an important concern, little is known about real world dexamethasone dosing in patients hospitalized with COVID-19 in the United States. We conducted a descriptive study to assess dexamethasone daily dose in adults with COVID-19 in a large US hospital network, overall and by respiratory support requirements, extracted using semi-structured nursing notes.

In November 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for baricitinib to be used in combination with remdesivir to treat COVID-19 in hospitalized patients on respiratory support (i.e., supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation). In June 2021, the FDA issued an EUA for tocilizumab to treat COVID-19 in hospitalized patients receiving systemic corticosteroids and on respiratory support. To understand the scope of utilization and characteristics of users of baricitinib and tocilizumab in the context of COVID-19, FDA conducted a descriptive analysis among patients with inpatient baricitinib or tocilizumab use in the Sentinel System. Both products were commercially available prior to FDA issuance of the EUAs, and the study period for this analysis (April 1, 2020, to March 31, 2021) included time prior to FDA issuance of these EUAs. Specific characteristics assessed included evidence of COVID-19, use of respiratory support, concomitant drug use, and medical conditions.

Results indicated that most patients who received inpatient baricitinib/remdesivir therapy had evidence of COVID-19. However, about half of patients who received inpatient baricitinib therapy did not appear to have concurrent remdesivir use, and few patients with inpatient baricitinib therapy appeared to have documented respiratory support at drug therapy initiation. Results also indicated that most patients with inpatient tocilizumab therapy had evidence of COVID-19 and a majority had concurrent systemic corticosteroid therapy. Additionally, around 25% of patients with tocilizumab therapy had documented mechanical ventilation at drug therapy initiation.  This analysis informed the FDA’s active safety monitoring efforts for products authorized or used for the treatment of COVID-19. FDA approved these products for the treatment of adults with COVID-19 in May 2022 (baricitinib) and December 2022 (tocilizumab), and EUAs remain in place for use in pediatric patients as of August 2023.
 

The Coronavirus Disease 2019 (COVID-19) was first detected in the United States in January 2020. Early studies indicated a disproportionate burden of COVID-19 infections, hospitalizations, and deaths among racial and ethnic minority groups. Importantly, these early studies were limited in geographic scope, and/or focused only on elderly and higher-risk adults. The COVID-19 pandemic, thus, presented the FDA with a unique opportunity to evaluate race and ethnicity-related data pertaining to COVID-19 testing, hospitalizations, and other outcomes, including disease severity and mortality. FDA’s studies in the Sentinel System sought to expand upon the current understanding of COVID-19-related outcomes among insured adult patients under 65 years old by geographic region over the year-long study period, using Sentinel’s rapid Sentinel Distributed Database (SDD), TriNetX Network, and PCORnet data sources.

The rapid SDD analysis found up to 42% of insured individuals with COVID-19 had missing race information, and patients with unknown race were younger and healthier. Results also indicated that minoritized individuals with COVID-19 have increased odds of COVID-19 hospitalization, critical COVID-19, and 30-day in-hospital mortality after controlling for baseline differences.

An analysis conducted in the PCORnet Distributed Data Network identified approximately 580,000 patients with any evidence of COVID-19 and approximately 73,000 with evidence of inpatient COVID-19 between April 2020 and March 2021. Data on race and ethnicity were well-populated in this electronic health record data source, especially compared to claims data sources (<9% of all eligible patients had missing race data). While there were no statistically significant differences in the racial composition of the "all eligible" and "any COVID-19" cohorts, patients of "Black or African American" and "Other" race were disproportionately present in the hospitalized COVID-19 cohort (21.2% vs 14.3% for Black and 9.3 vs 5.9% for Other). Apparent differences in clinical observation and laboratory results existed between racial/ethnic minoritized groups compared to patients of White race and/or Non-Hispanic ethnicity, but interpretation of these findings was difficult due to lack of standardization. Future work should examine to what extent clinical and laboratory data can be used to understand potential racial and ethnic differences in COVID-19.

This study raised awareness of the extent of missingness of race and ethnicity in administrative claims data used for regulatory purposes. This evaluation of missing race and ethnicity data provoked innovative thinking of approaches to improve the capture of race data in the Sentinel Distributed Database. Building a full picture of the associations between race and ethnicity and COVID-19 outcomes will continue efforts to characterize the full impact of the COVID-19 pandemic. As this study intended to characterize the burden of COVID-19 outcomes, FDA did not take any regulatory action based on these data.

This project was funded by U.S. Food and Drug Administration (FDA) Office of Minority Health and Health Equity (OMHHE).
 

On April 5, 2022, the Biden Administration issued a Presidential Memorandum directing the Secretary of Health and Human Services (HHS) to coordinate a new effort across the federal government to develop and issue the first-ever interagency national research action plan on “long COVID,” a term used to describe the long-lasting effects of having been infected with COVID-19. In response, FDA’s Office of Surveillance and Epidemiology (OSE) formed a working group tasked with outlining OSE's research plan on long COVID for fiscal years 2023-2024. As part of these efforts, an analysis was conducted to explore the use of FDA Sentinel’s electronic health record (EHR) data sources (specifically TriNetX) to identify and characterize long COVID, specific outcomes associated with long COVID, and relevant covariates (e.g., COVID-19 vaccination, prior COVID-19 infection, and treatments received during the acute disease phase). Results found under capture of long COVID cases in EHR data, with the most frequent signs/symptoms being in line with what has been reported in the literature.

COVID-19 vaccination has been delivered in a wide range of settings, from healthcare delivery visits to state sponsored vaccination fairs. Therefore, complete capture of vaccination status may benefit from using multiple code types, such as claims and CVX (vaccine administered) state-based Immunization Information Systems (CVX-IIS) codes, to enhance the ascertainment.

This poster aims to characterize the availability and code type of COVID-19 vaccine data in the Sentinel Distributed Database (SDD). It was presented at the 2024 ISPE Annual Meeting.
 

There is a significant void in our understanding of the specific medications utilized by pregnant women with COVID-19 in real-world outpatient settings. Existing evidence refers to small populations or inpatient prescriptions only.

This poster estimates medicines use prevalence by pregnancy trimester in non-hospitalized pregnant women with COVID-19 and compare it with pregnant women without COVID-19 and non-pregnant women with COVID-19. It was presented at the 2024 ISPE Annual Meeting.
 

COVID-19 may increase the risk of developing severe illness among pregnant individuals. Several studies have described clinical characteristics and complications among pregnancies with COVID-19, but data on the impact of maternal COVID-19 on adverse infant outcomes is limited. 

This presentation implements the CONSIGN protocol (COVID-19 infection and medicines in pregnancy), as part of an international collaboration across Europe, USA, and Canada, to examine the risk of adverse outcomes in infants delivered by pregnant individuals with COVID-19 compared to pregnant individuals without COVID-19. It was presented at the 2024 ISPE Annual Meeting.