Orenstein Evan W, De Serres Gaston, Haber Michael J, Shay David K, Bridges Carolyn B, Gargiullo Paul, Orenstein Walter A
Yale University, New Haven, CT, USA.
Int J Epidemiol. 2007 Jun;36(3):623-31. doi: 10.1093/ije/dym021. Epub 2007 Apr 2.
Influenza causes substantial morbidity and annual vaccination is the most important prevention strategy. Accurately measuring vaccine effectiveness (VE) is difficult. The clinical syndrome most closely associated with influenza virus infection, influenza-like illness (ILI), is not specific. In addition, laboratory confirmation is infrequently done, and available rapid diagnostic tests are imperfect. The objective of this study was to estimate the joint impact of rapid diagnostic test sensitivity and specificity on VE for three types of study designs: a cohort study, a traditional case-control study, and a case-control study that used as controls individuals with ILI who tested negative for influenza virus infection.
We developed a mathematical model with five input parameters: true VE, attack rates (ARs) of influenza-ILI and non-influenza-ILI and the sensitivity and specificity of the diagnostic test.
With imperfect specificity, estimates from all three designs tended to underestimate true VE, but were similar except if fairly extreme inputs were used. Only if test specificity was 95% or more or if influenza attack rates doubled that of background illness did the case-control method slightly overestimate VE. The case-control method usually produced the highest and most accurate estimates, followed by the test-negative design. The bias toward underestimating true VE introduced by low test specificity increased as the AR of influenza- relative to non-influenza-ILI decreases and, to a lesser degree, with lower test sensitivity.
Demonstration of a high influenza VE using tests with imperfect sensitivity and specificity should provide reassurance that the program has been effective in reducing influenza illnesses, assuming adequate control of confounding factors.
流感会导致大量发病情况，每年接种疫苗是最重要的预防策略。准确测量疫苗效力（VE）具有难度。与流感病毒感染最密切相关的临床综合征，即流感样疾病（ILI），并不具有特异性。此外，很少进行实验室确诊，且现有的快速诊断测试并不完美。本研究的目的是估计快速诊断测试的敏感性和特异性对三种研究设计的疫苗效力的联合影响：队列研究、传统病例对照研究以及将流感病毒感染检测呈阴性的ILI患者作为对照的病例对照研究。
我们开发了一个具有五个输入参数的数学模型：真实疫苗效力、流感ILI和非流感ILI的发病率（ARs）以及诊断测试的敏感性和特异性。
在特异性不完美的情况下，所有三种设计的估计值往往会低估真实疫苗效力，但除了使用相当极端的输入值外，这些估计值相似。只有当测试特异性为95%或更高，或者流感发病率是背景疾病发病率的两倍时，病例对照方法才会略微高估疫苗效力。病例对照方法通常产生最高且最准确的估计值，其次是检测阴性设计。随着流感相对于非流感ILI的发病率降低，以及在较小程度上随着测试敏感性降低，低测试特异性导致的低估真实疫苗效力的偏差会增加。
假设对混杂因素进行了充分控制，使用敏感性和特异性不完美的测试证明高流感疫苗效力应能让人放心该计划在减少流感疾病方面是有效的。
