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-Barre´ 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.
| Original language | English |
|---|---|
| Article number | n1435 |
| Journal | The BMJ |
| Volume | 373 |
| DOIs | |
| Publication status | Published - 14 Jun 2021 |
Bibliographical note
Funding Information:authors approved the final version and had final responsibility for the decision to submit for publication. PRR, MAS, PBR, GH, and DPA are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: This work was partially funded by the UK National Institute for Health Research (NIHR), European Medicines Agency, European Health Data and Evidence Network (EHDEN), US Food and Drug Administration CBER BEST initiative (75F40120D00039), and US National Library of Medicine (R01 LM006910). EHDEN has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. The Innovative Medicines Initiative 2 Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The study funders had no role in the conceptualisation, design, data collection, analysis, decision to publish, or preparation of the manuscript. Competing interests: All authors have completed the ICMJE disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare the following interests: DPA receives funding from the UK National Institute for Health Research (NIHR) in the form of a senior research fellowship and the Oxford NIHR Biomedical Research Centre. XL receives the Clarendon Fund and Brasenose College Scholarship (University of Oxford) to support her DPhil study. DPA’s research group has received research grants from the European Medicines Agency; the Innovative Medicines Initiative; Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, and UCB Biopharma. GH and AO receive funding from the US National Institutes of Health (NIH) and the US Food and Drug Administration. KV and PR work for a research group that receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, Novartis, GSK, Amgen, and Chiesi, none of which relates to the content of this paper. PBR, RM, AS, GR, and AGS are employees of Janssen Research and Development and shareholders in Johnson and Johnson. MAS receives grants and contracts from the FDA and the US Department of Veterans Affairs within the scope of this research, and grants and contracts from NIH, IQVIA, and Private Health Management outside the scope of this research. Ethical approval: The protocol for this research was approved by the independent scientific advisory committee for Medicine and Healthcare products Regulatory Agency database research (protocol number 20_000211), the IDIAPJGol (Fundacio Institut Universitari per a la recerca a l’Atencio Primaria de Salut Jordi Gol i Gurina) clinical research ethics committee (project code: 21/007-PCV), the Integrated Primary Care Information governance board (application number 3/2021), and Columbia University institutional review board (AAAO7805).
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