Methods for Evaluating Vaccine Efficacy

评估疫苗功效的方法

• 批准号: 9042201
• 负责人: M Elizabeth Halloran
• 金额: $ 48.8万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9042201
• 关键词: Accounting; Bayesian Method; Case-Control Studies; Characteristics; Cluster randomized trial; Collection; Complex; Computer Simulation; Dengue; Development; Disease; Effectiveness; Epidemiologic Methods; Event; Exposure to; Future; Health Policy; Heterogeneity; Household; Human; Immune; Immunity; Individual; Infection; Influenza; Instruction; Joints; Measures; Methods; Modeling; Policies; Population; Primary Infection; Property; Public Health; Randomized; Recording of previous events; Research; Research Design; Risk; Rotavirus; Rotavirus Vaccines; Statistical Methods; Statistical Study; Survival Analysis; Tuberculosis; Tuberculosis Vaccines; Typhoid Fever; Vaccination; Vaccines; base; clinical efficacy; cost effective; cross immunity; design; influenza virus vaccine; malaria transmission; malaria transmission-blocking vaccine; novel; novel vaccines; protective effect; randomized trial; transmission process; vaccination strategy; vaccine candidate; vaccine effectiveness; vaccine efficacy; vaccine trial

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.

对疫苗接种的直接、间接、总体和总体影响的有效估计对于监管和预防至关重要。 政策决定。新疫苗对新颖的统计方法和研究设计提出了新的挑战。我们 提出了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。我们的方法是由特定疫苗激发的，但在大多数情况下 病例适用于具有相似特性的疫苗。在目标 1 中，我们将开发新颖的集群- 用于评估新登革热疫苗效果和评估间接影响的随机设计 疟疾传播阻断候选者。在目标 2 中，我们将开发新的统计方法 估计异质性下多价疫苗的功效并分析当前登革热疫苗的试验 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替代品 免受一系列试验的保护。我们将使用这些方法来探索候选一般代理 轮状病毒疫苗，我们将开发验证新疫苗保护的免疫相关性的方法 A 型脑膜炎球菌疫苗。在目标 4 中，我们将开发评估疫苗传染性功效的方法 根据两级聚类的研究并估计流感疫苗的数量。我们将开发一个 新的风险衡量标准称为潜在风险并描述其特征。在目标 5 中，我们将开发两个 用于评估新的候选结核疫苗的新颖设计。第一个是随机案例参考 设计将成为在大量人群中评估新结核病疫苗的一种经济有效的方法。这 第二个设计考虑了先前的敏化，并允许区分不同的效果 针对原发感染或再激活引起的疾病的疫苗。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。结果将直接贡献于 监管和公共卫生政策决策，以及“作为计算机模拟的输入来探索 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（参见说明）： 准确评估疫苗的直接、间接、总体和总体效应对于监管和预防至关重要。 政策决定。这里提出的研究将对实施实际产生直接影响 研究评估当前可用和未来疫苗的效果，从而直接为公众做出贡献 健康。研究结果也将有助于计算机模拟最佳疫苗接种策略。