{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:07:37Z","timestamp":1789988857045,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases -NIAID","doi-asserted-by":"crossref","award":["1R01AI107721"],"award-info":[{"award-number":["1R01AI107721"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality - AHRQ","doi-asserted-by":"crossref","award":["R00HS022193"],"award-info":[{"award-number":["R00HS022193"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>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\u2010controlled design to investigate the safety of concomitant vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010examining the known increase in risk of seizure 7 to 10 days after measles\u2010mumps\u2010rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u20131.6), <jats:italic>P<\/jats:italic> value\u00a0=\u00a0\u03b8.226.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have shown that when using a self\u2010controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time\u2010invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4399","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T01:31:01Z","timestamp":1518571861000},"page":"405-412","source":"Crossref","is-referenced-by-count":6,"title":["Methods for addressing \u201cinnocent bystanders\u201d when evaluating safety of concomitant vaccines"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7761-7090","authenticated-orcid":false,"given":"Shirley V.","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Department of Medicine Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurrahman","family":"Abdurrob","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Department of Medicine Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Spoendlin","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Department of Medicine Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Lewis","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Vaccine Study Center, Kaiser Permanente Division of Research  Oakland CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6664-3266","authenticated-orcid":false,"given":"Sophia R.","family":"Newcomer","sequence":"additional","affiliation":[{"name":"Institute for Health Research Kaiser Permanente Colorado  Denver CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Fireman","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Vaccine Study Center, Kaiser Permanente Division of Research  Oakland CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F.","family":"Daley","sequence":"additional","affiliation":[{"name":"Institute for Health Research Kaiser Permanente Colorado  Denver CO USA"},{"name":"Department of Pediatrics University of Colorado School of Medicine  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Glanz","sequence":"additional","affiliation":[{"name":"Institute for Health Research Kaiser Permanente Colorado  Denver CO USA"},{"name":"Colorado School of Public Health University of Colorado Denver  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Duffy","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kulldorff","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Department of Medicine Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.04.097"},{"key":"e_1_2_7_3_1","volume-title":"The Childhood Immunization Schedule and Safety: Stakeholders Concerns, Scientific Evidence, and Future Studies","author":"Institute of Medicine (IOM)","year":"2013"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-0400"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.106.5.1097"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002227"},{"issue":"1","key":"e_1_2_7_7_1","first-page":"A1\u2010A29","article-title":"White Paper on studying the safety of the childhood immunization schedule in the Vaccine Safety Datalink","volume":"34","author":"Glanz JM","year":"2016","journal-title":"Vaccine."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-3154"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","unstructured":"SmithPJ HumistonSG MarcuseEK et al.Parental delay or refusal of vaccine doses childhood vaccination coverage at 24 months of age and the Health Belief Model.Public health reports (Washington D.C.: 1974). 2011;126 Suppl 2:135\u2013146.","DOI":"10.1177\/00333549111260S215"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.01.096"},{"issue":"1","key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/01.inf.0000437806.76221.20","article-title":"Safety and immunogenicity of a toddler dose following an infant series of a hexavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b, hepatitis B vaccine administered concurrently or at separate visits with a heptavalent pneumococcal conjugate vaccine","volume":"33","author":"Halperin SA","year":"2014","journal-title":"Pediatr Infect Dis J"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000114902.84651.02"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.24873"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-0635"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-0320"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3429"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-0665"},{"key":"e_1_2_7_18_1","unstructured":"CDC. 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