title: Four different study designs to evaluate vaccine safety were equally validated with contrasting limitations.
abstract: OBJECTIVE
  We conducted a simulation study to empirically compare four study designs [cohort, case-control, risk-interval, self-controlled case series (SCCS)] used to assess vaccine safety.
  
  
  METHODS
  Using Vaccine Safety Datalink data (a Centers for Disease Control and Prevention-funded project), we simulated 250 case sets of an acute illness within a cohort of vaccinated and unvaccinated children. We constructed the other three study designs from the cohort at three different incident rate ratios (IRRs, 2.00, 3.00, and 4.00), 15 levels of decreasing disease incidence, and two confounding levels (20%, 40%) for both fixed and seasonal confounding. Each of the design-specific study samples was analyzed with a regression model. The design-specific beta; estimates were compared.
  
  
  RESULTS
  The beta; estimates of the case-control, risk-interval, and SCCS designs were within 5% of the true risk parameters or cohort estimates. However, the case-control's estimates were less precise, less powerful, and biased by fixed confounding. The estimates of SCCS and risk-interval designs were biased by unadjusted seasonal confounding.
  
  
  CONCLUSIONS
  All the methods were valid designs, with contrasting strengths and weaknesses. In particular, the SCCS method proved to be an efficient and valid alternative to the cohort method.
authors.affiliation: Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO 80237-8066, USA. jason.m.glanz@kp.org
authors.forename: Jason M
authors.initials: JM
authors.lastname: Glanz
authors.forename: David L
authors.initials: DL
authors.lastname: McClure
authors.forename: Stanley
authors.initials: S
authors.lastname: Xu
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hambidge
authors.forename: Martin
authors.initials: M
authors.lastname: Lee
authors.forename: Margarette S
authors.initials: MS
authors.lastname: Kolczak
authors.forename: Ken
authors.initials: K
authors.lastname: Kleinman
authors.forename: John P
authors.initials: JP
authors.lastname: Mullooly
authors.forename: Eric K
authors.initials: EK
authors.lastname: France
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D015982:Bias; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006302:Health Services Research / Q000379:methods*; D006801:Humans; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000009:adverse effects*; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012107:Research Design; D013997:Time Factors
chemical_list: D022542:Measles-Mumps-Rubella Vaccine