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（VE）的系统。本研究的目的是：1）在非住院人群队列中生成用于预防实验室确诊流感的直接VE的年度估计值; 2）在流感季节定期提供VE的快速评估; 3）提供高风险年龄组疫苗有效性的估计值。马什菲尔德诊所（MC）的基础设施提供了三个关键优势，以进行这项研究：l）一个明确的，稳定的人口队列，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，或梅萨）; 2）一个全面的，实时的，基于互联网的免疫登记，包括所有公共和私人免疫服务提供者为这一人群;以及3）一个有效的综合征监测系统，以迅速发现需要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，使用基于梅萨人群的固定队列。队列将分为以下年龄层：6-23个月、24个月至8岁、9-17岁、18-49岁、50-64岁和65岁以上。该队列将于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患有某些慢性疾病进一步分为高风险和正常风险。我们将识别并招募在流感流行期间患有MAARI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岁的成人。我们将对其他年龄组（2岁至49岁）发生的MAARI采用抽样策略。将采集入组患者的鼻或鼻咽拭子进行病毒培养。将使用两种程序识别和入组MAARI患者：1）在儿科或急诊科诊所访视期间进行当天招募，2）使用症状监测进行次日入组，这将识别前一天在所有MC地点进行MAARI访视的患者。 分析：流感疫苗的有效性将估计为VE=1-RR，其中RR表示接种组与未接种组相比实验室确认流感的相对风险。最初，流感研究队列的所有成员将按照MAARI状态、疫苗接种状态、年龄组和高风险状态进行分层。在每个MAARI分层中，将为入组受试者分配一个分析权重，该分析权重等于分层研究队列中的人数除以分层入组受试者人数。总体VE估计值将根据年龄组、高风险状态和资源利用进行调整。我们将计算流感季节第4、8和12周的累积VE估计值。此外，将计算第5-8周和第9-12周的单独4周估计值。我们将使用各种分析程序来识别偏倚和混淆的潜在来源。将向CDC提供VE的中期和年度估计值（95%置信区间），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.