Shirley V Wang1, Abdurrahman Abdurrob1, Julia Spoendlin1, Edwin Lewis2, Sophia R Newcomer3, Bruce Fireman2, Matthew F Daley3,4, Jason M Glanz3,5, Jonathan Duffy6, Eric S Weintraub6, Martin Kulldorff1. 1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Department of Medicine, Harvard Medical School, Boston, MA, USA. 2. Kaiser Permanente Vaccine Study Center, Kaiser Permanente Division of Research, Oakland, CA, USA. 3. Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA. 4. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA. 5. Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA. 6. Centers for Disease Control and Prevention, Atlanta, GA, USA.
Abstract
PURPOSE: The need to develop methods for studying the safety of childhood immunization schedules has been recognized by the Institute of Medicine and Department of Health and Human Services. The recommended childhood immunization schedule includes multiple vaccines in a visit. A key concern is safety of concomitant (same day) versus separate day vaccination. This paper addresses a methodological challenge for observational studies using a self-controlled design to investigate the safety of concomitant vaccination. METHODS: We propose a process for distinguishing which of several concomitantly administered vaccines is responsible for increased risk of an adverse event while adjusting for confounding due to relationships between effect modifying risk factors and concomitant vaccine combinations. We illustrate the approach by re-examining the known increase in risk of seizure 7 to 10 days after measles-mumps-rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines. RESULTS: Initial analyses suggested that DTaP had both an independent and potentiating effect on seizure. After accounting for the relationship between age at vaccination and vaccine combination, there was little evidence for increased risk of seizure with same day administration of DTaP and MMR; incidence rate ratio, 95% confidence interval 1.2 (0.9-1.6), P value = θ.226. CONCLUSION: We have shown that when using a self-controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time-invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules.
PURPOSE: The need to develop methods for studying the safety of childhood immunization schedules has been recognized by the Institute of Medicine and Department of Health and Human Services. The recommended childhood immunization schedule includes multiple vaccines in a visit. A key concern is safety of concomitant (same day) versus separate day vaccination. This paper addresses a methodological challenge for observational studies using a self-controlled design to investigate the safety of concomitant vaccination. METHODS: We propose a process for distinguishing which of several concomitantly administered vaccines is responsible for increased risk of an adverse event while adjusting for confounding due to relationships between effect modifying risk factors and concomitant vaccine combinations. We illustrate the approach by re-examining the known increase in risk of seizure 7 to 10 days after measles-mumps-rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines. RESULTS: Initial analyses suggested that DTaP had both an independent and potentiating effect on seizure. After accounting for the relationship between age at vaccination and vaccine combination, there was little evidence for increased risk of seizure with same day administration of DTaP and MMR; incidence rate ratio, 95% confidence interval 1.2 (0.9-1.6), P value = θ.226. CONCLUSION: We have shown that when using a self-controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time-invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules.
Authors: Philip J Smith; Sharon G Humiston; Edgar K Marcuse; Zhen Zhao; Christina G Dorell; Cynthia Howes; Beth Hibbs Journal: Public Health Rep Date: 2011 Jul-Aug Impact factor: 2.792
Authors: Simon J Hambidge; Sophia R Newcomer; Komal J Narwaney; Jason M Glanz; Matthew F Daley; Stan Xu; Jo Ann Shoup; Ali Rowhani-Rahbar; Nicola P Klein; Grace M Lee; Jennifer C Nelson; Marlene Lugg; Allison L Naleway; James D Nordin; Eric Weintraub; Frank DeStefano Journal: Pediatrics Date: 2014-06 Impact factor: 7.124
Authors: Mirjam J Knol; Tyler J VanderWeele; Rolf H H Groenwold; Olaf H Klungel; Maroeska M Rovers; Diederick E Grobbee Journal: Eur J Epidemiol Date: 2011-02-23 Impact factor: 8.082
Authors: Alison Tse Kawai; David Martin; Martin Kulldorff; Lingling Li; David V Cole; Cheryl N McMahill-Walraven; Nandini Selvam; Mano S Selvan; Grace M Lee Journal: Pediatrics Date: 2015-09-14 Impact factor: 7.124
Authors: Nicola P Klein; Bruce Fireman; W Katherine Yih; Edwin Lewis; Martin Kulldorff; Paula Ray; Roger Baxter; Simon Hambidge; James Nordin; Allison Naleway; Edward A Belongia; Tracy Lieu; James Baggs; Eric Weintraub Journal: Pediatrics Date: 2010-06-29 Impact factor: 7.124
Authors: Robert J Yetman; Julie S Shepard; Anton Duke; Jon E Stek; Maria Petrecz; Stephanie O Klopfer; Barbara J Kuter; Florian P Schödel; Andrew W Lee Journal: Hum Vaccin Immunother Date: 2013-06-06 Impact factor: 3.452
Authors: Teresa M Hesley; Keith S Reisinger; Bradley J Sullivan; Erin H Jensen; Susan Stasiorowski; Cathy Meechan; Christina Y Chan; David J West Journal: Pediatr Infect Dis J Date: 2004-03 Impact factor: 2.129
Authors: Scott A Halperin; Bruce Tapiéro; Marc Dionne; William Meekison; Francisco Diaz-Mitoma; Paul Zickler; Earl Rubin; Joanne Embree; Prakash Bhuyan; Andrew Lee; Minran Li; Antigona Tomovici Journal: Pediatr Infect Dis J Date: 2014-01 Impact factor: 2.129