Influenza Vaccination and Mortality: Differentiating Vaccine Effects From Bias

Abstract

It is widely believed that influenza (flu) vaccination of the elderly reduces all-cause mortality, yet randomized trials for assessing vaccine effectiveness are not feasible and the observational research has been controversial. Efforts to differentiate vaccine effectiveness from selection bias have been problematic. The authors examined mortality before, during, and after 9 flu seasons in relation to time-varying vaccination status in an elderly California population in which 115,823 deaths occurred from 1996 to 2005, including 20,484 deaths during laboratory-defined flu seasons. Vaccine coverage averaged 63%; excess mortality when the flu virus was circulating averaged 7.8%. In analyses that omitted weeks when flu circulated, the odds ratio measuring the vaccination-mortality association increased monotonically from 0.34 early in November to 0.56 in January, 0.67 in April, and 0.76 in August. This reflects the trajectory of selection effects in the absence of flu. In analyses that included weeks with flu and adjustment for selection effects, flu season multiplied the odds ratio by 0.954. The corresponding vaccine effectiveness estimate was 4.6% (95% confidence interval: 0.7, 8.3). To differentiate vaccine effects from selection bias, the authors used logistic regression with a novel case-centered specification that may be useful in other population-based studies when the exposure-outcome association varies markedly over time.

Reply: Letter to the Editor, Cochrane Rearranged

“…We found a mean effectiveness of 48% in the studies reviewed, contrasting sharply with the average effectiveness figure of 4.6% from the exceptional study by Fireman et al [4]; we explain the discrepancy as a healthy user effect, according to Simonson et al [5]. Consequently, we excluded all-cause mortality studies from our main analysis.…”

Vaccination and 30-Day Mortality Risk in Children, Adolescents, and Young Adults

“…Although there has been significant research conducted on deaths after vaccination in both infants and older adults, this study fills a void by investigating deaths among older children and young adults. 26,[40][41][42][43][44] We assessed deaths after vaccination on a population level as well as an individual level to provide a complete evaluation of vaccine safety with regard to death. This research should reassure the public with regard to the safety of 4vHPV vaccine, as well as other vaccines routinely administered to individuals 9 to 26 years of age.…”

“…[26][27][28][29][30][31] The case-centered method adjusts for seasonal variation in mortality and vaccine administration. In the analytic dataset, we included deaths of individuals who had received ≥1 vaccination in the year before death.…”

Measles-Mumps-Rubella-Varicella Combination Vaccine and the Risk of Febrile Seizures

“…For (c), we conducted casecentered logistic regressions by using a data set with only 1 record per seizure. 17 The dependent variable was whether the seizure occurred in the risk window; the key predictor was whether exposure was MMRV versus MMR ϩ varicella.…”