Methods for Evaluating Vaccine Efficacy

对疫苗接种的直接、间接、总和总体影响的有效估计对于监管和 政策决定。新疫苗对新的统计方法和研究设计提出了新的挑战。我们 提出一个雄心勃勃的研究议程，其中包括五个主要目标，以开发尖端方法 目前可用的和未来的疫苗。我们的方法是受特定疫苗的激励，但在大多数情况下 病例适用于具有类似特性的疫苗。在目标1中，我们将开发新的集群- 评估新登革热疫苗效果和间接影响的随机设计 阻止疟疾传播的候选人名单。在目标2中，我们将开发新的统计方法 异质性下多价疫苗的效力评估及当前登革热疫苗试验分析 候选人。在目标3中，我们将开发统计方法来评估和比较一般代用品 不受一系列审判的保护。我们将使用这些方法来探索候选的通用代理 轮状病毒疫苗，我们将开发方法来验证新的保护作用的免疫相关性 脑膜炎双球菌A疫苗。在目标4中，我们将开发评估传染性疫苗效力的方法。 从一项有两个水平的聚类的研究中得出，并估计流感疫苗的这一数量。我们将开发一种 新的风险衡量标准称为潜在风险敞口，并勾勒出其特征。在目标5中，我们将制定两个 评估新的候选结核病疫苗的新设计。第一个是随机病例参照。 这将是一种在大人口中评估新结核病疫苗的具有成本效益的方法。这个 其次是一种设计，它考虑到了先前的敏化，并将允许区分 因初次感染或重新激活而导致的疾病的疫苗。我们新颖的设计和分析方法将 对实际研究的实施有直接影响。这一结果将直接有助于 监管和公共卫生政策决策，以及被用作计算机模拟的输入，以探索 最佳疫苗接种策略。我们的研究将与个人和组织合作进行 直接参与疫苗研究。 相关性(请参阅说明)： 准确评估疫苗的直接、间接、总和总体影响对于监管和 政策决定。这里提出的研究将对实施实际情况产生直接影响 评估现有和未来疫苗效果的研究，从而直接为公众做出贡献 健康。这些结果也将有助于计算机模拟最佳的疫苗接种策略。

Valid estimates of the direct, indirect, total, and overall effects of vaccination are crucial for regulatory and policy decisions. New vaccines pose new challenges for novel statistical methods and study designs. We propose an ambitious research agenda in a collection of five main aims to develop cutting-edge methods for currently available and future vaccines. Our methods are motivated by particular vaccines, but in most cases are applicable to vaccines with similar characteristics. In Aim 1, we will develop novel cluster- randomized designs for evaluating the effects of new dengue vaccines and for evaluating the indirect effects of malaria transmission blocking candidates. In Aim 2, we will develop novel statistical methods for estimating efficacy of multivalent vaccines under heterogeneity and analyze trials of current dengue vaccine candidates. In Aim 3, we will develop statistical methods for evaluating and comparing general surrogates of protection from a collection of trials. We will use these methods to explore candidate general surrogates of rotavirus vaccines, We will develop methods for validating the immune correlate of protection of the new meningococcal A vaccine. In Aim 4, we will develop methods to estimate vaccine efficacy for infectiousness from a study with two levels of clustering and estimate this quantity for influenza vaccine. We will develop a new measure of risk called potential exposure and delineate its characteristics. In Aim 5, we will develop two novel designs for evaluating new candidate tuberculosis vaccines. The first is a randomized case-referent design that will be a cost-effective method to evaluate new tuberculosis vaccines in large populations. The second is a design that takes into account prior sensitization and will allow differentiation of the effects of vaccine on disease due to primary infection or reactivation. Our novel methods of design and analysis will have direct consequences for implementation of actual studies. The results will contribute directly to regulatory and public health policy decisions, as well as be used "as inputs in computer simulations to explore optimal vaccination strategies. Our research will take place in partnership with individuals and organizations directly involved with vaccine studies. RELEVANCE (See instructions): Accurate assessment of direct, indirect, total, and overall effects of vaccines is crucial for regulatory and policy decisions. The research proposed here would have direct consequences for implementing actual studies to evaluate effects of currently available and future vaccines, and thus contribute directly to public health. The results will also be useful for computer simulations of optimal vaccination strategies.