Rapid Analysis of Influenza Vaccine Effectiveness

背景：需要一种快速评估流感疫苗有效性的系统。这项研究的目的是 1)生成用于预防实验室确认的流感的直接VE的年度估计数 非制度化的以人口为基础的队列；2)在 流感季节；以及3)对高危年龄组的疫苗效力进行估计。马什菲尔德诊所 (MC)基础设施为开展此项研究提供了三个关键优势：L)定义明确、稳定的 大约50,000人生活在14个邮政编码(马什菲尔德流行病学研究区，或称MESA)；2)一个综合的， 基于互联网的实时免疫注册，包括提供此服务的所有公共和私人免疫提供者 人口；以及3)一个有效的综合征监测系统，以快速识别医疗护理的事件病例 急性呼吸道疾病(Maari)。 方法：这将是一项前瞻性队列研究，采用基于台地人群的固定队列。这群人 将分为以下年龄段：6-23个月，24个月至8岁，9-17岁，18-49岁， 五十岁，六十五岁以上。队列将于2004年11月1日确定，流感免疫状态将 被实时监控。每个年龄层将根据存在的情况进一步划分为高风险和正常风险。 或者没有某些慢性病。在此期间，我们将确定并招募具有MA.ARI的队列成员 流感流行期。我们将尝试将所有Maari病例登记在流感优先年龄组 建议接种疫苗：6个月至23个月大的儿童和50岁的成年人。我们将聘请一名 其他年龄组(2岁--49岁)的Maari抽样策略。鼻部或鼻咽部拭子可以 从登记的患者中收集进行病毒培养。Maari患者将被识别和登记，使用两个 程序：1)在儿科或紧急护理诊所就诊期间当天招募，以及2)第二天登记使用 症状监测，它将识别所有MC地点前一天有MAAR/来访的患者。 分析：流感疫苗的效力将被估计为VE=I-RR，其中RR表示 接种疫苗组与未接种组相比，实验室确认的流感。最初，所有成员 流感研究队列将按Maari状况、疫苗接种状况、年龄组和高年龄组进行分类 风险状态。在每个Maar/阶层中，登记的受试者将被分配一个等于人数的分析权重 在研究中，将该阶层的队列除以该阶层中登记的受试者的数量。总体VE估计将 根据年龄段、高危状态和资源利用情况进行调整。我们将按周计算累计VE估计值 流感季节的第4、8和12天。此外，将分别计算5-8周和9-12周的4周估计数。 我们将使用各种分析方法来确定产生偏见和混淆的潜在来源。中期和年度 将向CDC提供具有95%可信区间的VE估计，包括每个 优先年龄组。

BACKGROUND: A system to rapidly assess influenza vaccine effectiveness (VE) is needed. The aims of this research are to 1) generate annual estimates of direct VE for prevention of laboratory-confirmed influenza in a noninstitutionalized population-based cohort; 2) provide rapid assessment of VE at regular intervals during the influenza season; and 3) provide estimates of vaccine effectiveness in higher risk age groups. The Marshfield Clinic (MC) infrastructure offers three key strengths to conduct this research: l) a well-defined, stable population cohort of about 50,000 people living in 14 zip codes (Marshfield Epidemiologic Study Area, or MESA); 2) a comprehensive, real-time, internet-based immunization registry that includes all public and private immunization providers serving this population; and 3) a functioning syndromic surveillance system to rapidly identify incident cases of medically-attended acute respiratory illness (MAARI). METHODS: This will be a prospective cohort study using a fixed cohort based on the MESA population. The cohort will be divided into the following age strata: 6--23 months, 24 months through 8 years, 9--17 years, 18 49 years, 50--64 years, and 65+ years. The cohort will be defined on November 1, 2004, and influenza immunization status will be monitored in real-time. Each age strata will be further stratified into high-risk and normal-risk based on the presence or absence of certain chronic diseases. We will identify and enroll cohort members who have MA.ARI during the influenza epidemic period. We will attempt to enroll all MAARI cases in the priority age groups for whom influenza vaccine is recommended: children 6 months through 23 months old, and adults > 50 years old. We will employ a sampling strategy for MAARI occurring in other age groups (2 years--49 years). A nasal or nasopharyngeal swab will be collected from enrolled patients for viral culture. Patients with MAARI will be identified and enrolled using two procedures: 1) same-day recruitment during a clinic visit to Pediatrics or Urgent Care, and 2) next-day enrollment using syndromic surveillance, which will identify patients with MAAR/visits on the previous day at all MC locations. ANALYSIS: Efficacy of the influenza vaccine will be estimated as VE=I-RR where RR denotes the relative risk of laboratory-confirmed influenza in the vaccinated group compared to the unvaccinated group. Initially, all members of the influenza study cohort will be classified in strata defined by MAARI status, vaccination status, age group and high- risk status. In each MAAR/stratum, enrolled subjects will be assigned an analytic weight equal to the number of people in the study cohort for the stratum divided by the number of enrolled subjects in the stratum. Overall VE estimates will be adjusted for age group, high-risk status and resource utilization. We will compute cumulative VE estimates at weeks 4, 8 and 12 of the influenza season. In addition, separate 4-week estimates for weeks 5-8 and 9-12 will be computed. We will use a variety of analytic procedures to identify potential sources of bias and confounding. Interim and annual estimates of VE with 95% confidence intervals will be provided to CDC, including overall VE and VE for each of the priority age groups.