Core_plus_Option_A_B_Proposal for Influenza Vaccine Effectiveness Research

描述（由申请人提供）：由于几乎普遍推荐每年接种一次（所有年龄为6个月），出于伦理原因，只能进行流感疫苗有效性的观察性研究。然而，观察性研究的结果可能受到未被认识到的选择偏差的影响，识别和调整这些偏差的研究设计策略是必要的。我们建议估计流感疫苗在两个卫生系统中预防医疗护理流感的有效性，以及在密歇根州一组有儿童的家庭中预防所有严重程度流感的有效性。我们将在流感季节在多个门诊保健中心、三家医院和约300个登记的家庭进行监测，并将登记成人和儿科患者以及符合各种病例定义的家庭成员。将报告和验证疫苗接种状况，并考虑实验室确认的流感结果，以分别估计门诊、住院和家庭人口的疫苗有效性，并比较各研究之间的估计值。分析将采用检测阴性的控制方法——流感检测阳性的为病例，检测阴性的为对照。将在分析模型中评估和考虑疫苗有效性的修饰因素和混杂因素，如年龄、健康状况、家庭规模和组成、卫生保健利用、主观社会经济地位和卫生系统特征。

DESCRIPTION (provided by applicant): Because of near universal recommendation for annual vaccination (all aged 6 months) only observational studies of influenza vaccine effectiveness can be performed for ethical reasons. However, results from observational studies may be subject to unrecognized selection biases, and study design strategies to identify and adjust for these biases are necessary. We propose estimation of influenza vaccine effectiveness in preventing medically attended influenza in two health systems, and influenza of all severities in a cohort of households with children, in Michigan. We will conduct surveillance at multiple outpatient health centers, three hospitals, and in ~300 enrolled households during the influenza season, and will enroll adult and pediatric patients and household members meeting various case definitions. Vaccination status will be reported and validated, and considered with laboratory-confirmed influenza outcomes to estimate vaccine effectiveness separately for ambulatory, inpatient and household populations, with estimates compared across studies. Analyses will use a test-negative control approach-those testing positive for influenza are cases, those testing negative are controls. Modifiers and confounders of vaccine effectiveness such as age, health status, household size and composition, health care utilization, subjective socio-economic status, and health system characteristics will be assessed and considered in analytic models.