title: Adapting group sequential methods to observational postlicensure vaccine safety surveillance: results of a pentavalent combination DTaP-IPV-Hib vaccine safety study.
abstract: To address gaps in traditional postlicensure vaccine safety surveillance and to promote rapid signal identification, new prospective monitoring systems using large health-care database cohorts have been developed. We newly adapted clinical trial group sequential methods to this observational setting in an original safety study of a combination diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) conjugate vaccine (DTaP-IPV-Hib) among children within the Vaccine Safety Datalink population. For each prespecified outcome, we conducted 11 sequential Poisson-based likelihood ratio tests during September 2008-January 2011 to compare DTaP-IPV-Hib vaccinees with historical recipients of other DTaP-containing vaccines. No increased risk was detected among 149,337 DTaP-IPV-Hib vaccinees versus historical comparators for any outcome, including medically attended fever, seizure, meningitis/encephalitis/myelitis, nonanaphylactic serious allergic reaction, anaphylaxis, Guillain-Barré syndrome, or invasive Hib disease. In end-of-study prespecified subgroup analyses, risk of medically attended fever was elevated among 1- to 2-year-olds who received DTaP-IPV-Hib vaccine versus historical comparators (relative risk = 1.83, 95% confidence interval: 1.34, 2.50) but not among infants under 1 year old (relative risk = 0.83, 95% confidence interval: 0.73, 0.94). Findings were similar in analyses with concurrent comparators who received other DTaP-containing vaccines during the study period. Although lack of a controlled experiment presents numerous challenges, implementation of group sequential monitoring methods in observational safety surveillance studies is promising and warrants further investigation.
authors.affiliation: Biostatistics Unit, Group Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101, USA. nelson.jl@ghc.org
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Nelson
authors.forename: Onchee
authors.initials: O
authors.lastname: Yu
authors.forename: Clara P
authors.initials: CP
authors.lastname: Dominguez-Islas
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Cook
authors.forename: Do
authors.initials: D
authors.lastname: Peterson
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Greene
authors.forename: W Katherine
authors.initials: WK
authors.lastname: Yih
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Daley
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Jacobsen
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: Eric S
authors.initials: ES
authors.lastname: Weintraub
authors.forename: Karen R
authors.initials: KR
authors.lastname: Broder
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jackson
mesh_terms: D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects*; D015340:Epidemiologic Research Design; D005260:Female; D018073:Haemophilus Vaccines / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008297:Male; D008329:Managed Care Programs; D016017:Odds Ratio; D016012:Poisson Distribution; D011054:Poliovirus Vaccine, Inactivated / Q000009:adverse effects*; D011159:Population Surveillance / Q000379:methods*; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D011446:Prospective Studies; D012306:Risk; D014481:United States; D018074:Vaccines, Conjugate / Q000009:adverse effects
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D011054:Poliovirus Vaccine, Inactivated; D018074:Vaccines, Conjugate; C541234:diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine