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Determining Which of Several Simultaneously Administered Vaccines Increase Risk of an Adverse Event


  • Shirley V. Wang

    () (Brigham and Women’s Hospital and Harvard Medical School)

  • Kristina Stefanini

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Edwin Lewis

    (Kaiser Permanente Vaccine Study Center)

  • Sophia R. Newcomer

    (Institute for Health Research, Kaiser Permanente Colorado)

  • Bruce Fireman

    (Kaiser Permanente Division of Research)

  • Matthew F. Daley

    (Institute for Health Research, Kaiser Permanente Colorado
    University of Colorado School of Medicine)

  • Jason M. Glanz

    (Institute for Health Research, Kaiser Permanente Colorado
    University of Colorado Denver)

  • Jonathan Duffy

    (Immunization Safety Office, Centers for Disease Control and Prevention)

  • Eric Weintraub

    (Immunization Safety Office, Centers for Disease Control and Prevention)

  • Martin Kulldorff

    (Brigham and Women’s Hospital and Harvard Medical School)


Introduction Childhood immunization schedules often involve multiple vaccinations per visit. When increased risk of an adverse event is observed after simultaneous (same-day) vaccinations, it can be difficult to ascertain which triggered the adverse event. This methods paper discusses a systematic process to determine which of the simultaneously administered vaccine(s) are most likely to have caused an observed increase in risk of an adverse event. Methods We use an example from the literature where excess risk of seizure was observed 1 day after vaccination, but same-day vaccination patterns made it difficult to discern which vaccine(s) may trigger the adverse event. We illustrate the systematic identification process using a simulation that retained the observed pattern of simultaneous vaccination in an empirical cohort of vaccinated children. We simulated “true” effects for diphtheria–tetanus–acellular pertussis (DTaP) and pneumococcal conjugate (PCV) on risk of seizure the day after vaccination. We varied the independent and interactive effects of vaccines (on the multiplicative scale). After applying the process to simulated data, we evaluated risk of seizure 1 day after vaccination in the empirical cohort. Results In all simulations, we were able to determine which vaccines contributed to excess risk. In the empirical data, we narrowed the association with seizure from all vaccines in the schedule to three likely candidates, DTaP, PCV, and/or Haemophilus influenzae type B (HiB) (p

Suggested Citation

  • Shirley V. Wang & Kristina Stefanini & Edwin Lewis & Sophia R. Newcomer & Bruce Fireman & Matthew F. Daley & Jason M. Glanz & Jonathan Duffy & Eric Weintraub & Martin Kulldorff, 2020. "Determining Which of Several Simultaneously Administered Vaccines Increase Risk of an Adverse Event," Drug Safety, Springer, vol. 43(10), pages 1057-1065, October.
  • Handle: RePEc:spr:drugsa:v:43:y:2020:i:10:d:10.1007_s40264-020-00967-8
    DOI: 10.1007/s40264-020-00967-8

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