Characterising the background incidence rates of adverse events of special interest for covid-19 vaccines in eight countries: multinational network cohort study

Abstract

Objective To quantify the background incidence rates of 15 prespecified adverse events of special interest (AESIs) associated with covid-19 vaccines. Design Multinational network cohort study. Setting Electronic health records and health claims data from eight countries: Australia, France, Germany, Japan, the Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. Participants 126 661 070 people observed for at least 365 days before 1 January 2017, 2018, or 2019 from 13 databases. Main outcome measures Events of interests were 15 prespecified AESIs (non-haemorrhagic and haemorrhagic stroke, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, anaphylaxis, Bell’s palsy, myocarditis or pericarditis, narcolepsy, appendicitis, immune thrombocytopenia, disseminated intravascular coagulation, encephalomyelitis (including acute disseminated encephalomyelitis), Guillain-Barré syndrome, and transverse myelitis). Incidence rates of AESIs were stratified by age, sex, and database. Rates were pooled across databases using random effects meta-analyses and classified according to the frequency categories of the Council for International Organizations of Medical Sciences. Results Background rates varied greatly between databases. Deep vein thrombosis ranged from 387 (95% confidence interval 370 to 404) per 100 000 person years in UK CPRD GOLD data to 1443 (1416 to 1470) per 100 000 person years in US IBM MarketScan Multi-State Medicaid data among women aged 65 to 74 years. Some AESIs increased with age. For example, myocardial infarction rates in men increased from 28 (27 to 29) per 100 000 person years among those aged 18-34 years to 1400 (1374 to 1427) per 100 000 person years in those older than 85 years in US Optum electronic health record data. Other AESIs were more common in young people. For example, rates of anaphylaxis among boys and men were 78 (75 to 80) per 100 000 person years in those aged 6-17 years and 8 (6 to 10) per 100 000 person years in those older than 85 years in Optum electronic health record data. Meta-analytic estimates of AESI rates were classified according to age and sex. Conclusion This study found large variations in the observed rates of AESIs by age group and sex, showing the need for stratification or standardisation before using background rates for safety surveillance. Considerable population level heterogeneity in AESI rates was found between databases.

Adverse events of special interest for COVID-19 vaccines - background incidences vary by sex, age and time period and are affected by the pandemic

“…Nevertheless, recent large multi-country studies have shown considerable heterogeneity across populations, for example data reported from the ACCESS project, which showed similar magnitudes of heterogeneity in background rates (3). The pooled rates across databases from a study by the OHDSI group showed many similarities to our rates for AESIs that were included in both studies; in addition, they also reported variability across sites and databases (8). This further underscores that population heterogeneity needs to be taken into account in the evaluation of AESIs.…”

“…Comparing incidence rates that originate from different data sources may carry additional risk of systematic bias due to data-related differences between data sources. Indeed, large variations have been seen between different types of data such as electronic health records and claims data sources even when using harmonized type of analysis and outcome definitions (8). Using rates from randomised trials or spontaneous reporting data may induce even greater variability, related to the specific data collection mechanisms for these activities.…”

“…Local background rates are generally considered most appropriate for obvious reasons (7), but expected rates can also be better informed by availability of background rates from many different populations, time periods and areas, to understand variability and consistency of rates. Data on background rates of AESI for COVID-19 vaccines from some different areas have started to appear in the scientific literature, for example a multi-database study by the Observational Health Data Sciences and Informatics (OHDSI) community (8). These efforts are important, as a comprehensive and thorough monitoring of vaccine safety will be an essential component in addressing public concerns about the rapid COVID-19 vaccine development and deployment, and support efforts to address vaccine hesitancy.…”

Vaccines against Covid-19, venous thromboembolism, and thrombocytopenia. A population-based retrospective cohort study

“…This avoids potential systematic error and confounding caused by heterogeneity between healthcare databases. 20 Third, we examined the excess rates of various diagnostic definitions of usual and unusual site venous thromboembolism, with or without thrombocytopenia. This allows the analysis of the rates of specific clinical outcomes, and at the same time it gives an overview of the epidemiology of venous thromboembolism in people with Covid-19 and following vaccination.…”

Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2: a cohort analysis

“…Although reactogenicity endpoints are informative for assessing potential vaccine side effects, these trials are underpowered to study rare safety outcomes. Adverse events related to the ChAdOx1 vaccine include the rare (<1/1000 to ≥ 1/10 000) outcome venous thrombosis and the very rare (<1/10 000) outcome vaccine-induced immune thrombosis with thrombocytopenia syndrome 21,22 . Similarly, myocarditis and pericarditis outcomes possibly associated with BNT162b2 are expected to affect around 10 to 24 people per 10 million fully vaccinated people aged ≥ 30 years 23 .…”