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

  1. Xintong Li
  2. Anna Ostropolets
  3. Rupa Makadia
  4. Azza Shoaibi
  5. Gowtham Rao
  6. Anthony G Sena
  7. Eugenia Martinez-Hernandez
  8. Antonella Delmestri
  9. Katia Verhamme
  10. Peter R Rijnbeek
  11. Talita Duarte-Salles
  12. Marc A Suchard
  13. Patrick B Ryan
  14. George Hripcsak
  15. Daniel Prieto-Alhambra

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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.

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  1. Version published to 10.1136/bmj.n1435
  2. ScreenIT

    SciScore for 10.1101/2021.03.25.21254315: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: 13 The study protocol and analysis code are available at: https://github.com/ohdsi-studies/Covid19VaccineAesiIncidenceCharacterization Ethical approval: The protocol for this research was approved by the Independent Scientific Advisory Committee (ISAC) for MHRA Database Research (protocol number 20_000211), the IDIAPJGol Clinical Research Ethics Committee (project code: 21/007-PCV), the IPCI governance board (application number 3/2021), and the Columbia University Institutional Review Board (AAAO7805).
    IRB: 13 The study protocol and analysis code are available at: https://github.com/ohdsi-studies/Covid19VaccineAesiIncidenceCharacterization Ethical approval: The protocol for this research was approved by the Independent Scientific Advisory Committee (ISAC) for MHRA Database Research (protocol number 20_000211), the IDIAPJGol Clinical Research Ethics Committee (project code: 21/007-PCV), the IPCI governance board (application number 3/2021), and the Columbia University Institutional Review Board (AAAO7805).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The primary limitation of this study is that all outcomes may have been subject to measurement error. As the outcome definitions were based on the presence of specific diagnostic codes and were not validated further, they may have had imperfect sensitivity or specificity. The analysis relied on data from 2017 to 2019 using a target population of all people in each database with >365 days of observation indexed on 1 January, 365 days’ time-at-risk, and outcome-specific clean windows to allow for recurrent events. The impact of these design decisions should be explored further.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.03.25.21254315 on medRxiv