title: Characterizing vaccine-associated risks using cubic smoothing splines.
abstract: Estimating risks associated with the use of childhood vaccines is challenging. The authors propose a new approach for studying short-term vaccine-related risks. The method uses a cubic smoothing spline to flexibly estimate the daily risk of an event after vaccination. The predicted incidence rates from the spline regression are then compared with the expected rates under a log-linear trend that excludes the days surrounding vaccination. The 2 models are then used to estimate the excess cumulative incidence attributable to the vaccination during the 42-day period after vaccination. Confidence intervals are obtained using a model-based bootstrap procedure. The method is applied to a study of known effects (positive controls) and expected noneffects (negative controls) of the measles, mumps, and rubella and measles, mumps, rubella, and varicella vaccines among children who are 1 year of age. The splines revealed well-resolved spikes in fever, rash, and adenopathy diagnoses, with the maximum incidence occurring between 9 and 11 days after vaccination. For the negative control outcomes, the spline model yielded a predicted incidence more consistent with the modeled day-specific risks, although there was evidence of increased risk of diagnoses of congenital malformations after vaccination, possibly because of a "provider visit effect." The proposed approach may be useful for vaccine safety surveillance.
authors.forename: M Alan
authors.initials: MA
authors.lastname: Brookhart
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Walker
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Laura
authors.initials: L
authors.lastname: Polakowski
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Corrie
authors.initials: C
authors.lastname: Paeglow
authors.forename: Tosmai
authors.initials: T
authors.lastname: Puenpatom
authors.forename: Hector
authors.initials: H
authors.lastname: Izurieta
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Daniel
mesh_terms: D019433:Chickenpox Vaccine / Q000009:adverse effects; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D005076:Exanthema / Q000453:epidemiology / Q000209:etiology; D005334:Fever / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D007223:Infant; D008458:Measles Vaccine / Q000009:adverse effects; D015233:Models, Statistical; D009108:Mumps Vaccine / Q000009:adverse effects; D016012:Poisson Distribution; D012044:Regression Analysis; D018570:Risk Assessment; D012411:Rubella Vaccine / Q000009:adverse effects; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects; D014612:Vaccines / Q000009:adverse effects*
chemical_list: D019433:Chickenpox Vaccine; D008458:Measles Vaccine; D009108:Mumps Vaccine; D012411:Rubella Vaccine; D014612:Vaccines