Rapid Analysis of Influenza Vaccine Effectiveness

描述(由申请人提供)： 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)在非制度化的人群队列中产生用于预防实验室确认的流感的直接VE的年度估计；2)在流感季节期间定期提供VE的快速评估；以及3)提供对高危年龄组疫苗有效性的估计。马什菲尔德诊所(MC)的基础设施为开展这项研究提供了三个关键优势：1)一个定义明确、稳定的人群队列，约50,000人，生活在14个邮政编码地区(马什菲尔德流行病学研究区，简称MESA)；2)一个全面的、实时的、基于互联网的免疫注册系统，其中包括为这些人群提供服务的所有公共和私人免疫提供者；3)一个运转良好的症状监测系统，以快速识别有医疗护理的急性呼吸道疾病(MAARI)病例。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。队列将分为以下年龄层：6-23个月，24个月-8岁，9-17岁，18-49岁，50-岁，65岁以上。队列将于2004年11月1日确定，并将实时监测流感免疫状况。每个年龄层将根据是否有某些慢性病被进一步划分为高风险和正常风险。我们将确定和招募在流感流行期间患有马利氏病的队列成员。我们将尝试将所有Maari病例纳入推荐接种流感疫苗的优先年龄组：6个月至23个月的儿童和50岁的成年人。我们将对发生在其他年龄组(2岁-49岁)的Maari采取抽样策略。将从登记的患者身上采集鼻拭子或鼻咽拭子进行病毒培养。MAARI患者将通过两个程序进行识别和登记：1)在儿科或紧急护理诊所就诊期间当天招募，2)使用症状监测进行第二天登记，这将识别前一天在所有MC地点就诊的MAARI患者。 分析：流感疫苗的效力将被估计为VE=1-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的相对风险。最初，流感研究队列的所有成员将按Maari状态、疫苗接种状态、年龄组和高危状态定义的层级进行分类。在每个Maari层，登记的受试者将被分配一个分析权重，等于该层的研究队列中的人数除以该层中登记的受试者的数目。总体VE估计将根据年龄组、高风险状态和资源利用率进行调整。我们将在流感季节的第4周、第8周和第12周计算累积VE估计数。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。将向疾控中心提供具有95%可信区间的VE中期和年度估计，包括每个优先年龄组的总体VE和VE。

DESCRIPTION (provided by applicant): 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 MAARI 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 MAARI visits on the previous day at all MC locations. ANALYSIS: Efficacy of the influenza vaccine will be estimated as VE=1-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 highrisk status. In each MAARI 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.