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; 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.

疫苗接种的直接，间接，总和总体影响的有效估计对于调节性和 政策决策。新疫苗对新型统计方法和研究设计提出了新的挑战。我们 提出雄心勃勃的研究议程，以五个主要目的，以开发尖端方法 目前可用和未来的疫苗。我们的方法是由特定疫苗激励的，但在大多数疫苗中 病例适用于具有相似特征的疫苗。在AIM 1中，我们将开发新颖的集群 - 随机设计用于评估新登革热疫苗的影响并评估间接效应 疟疾传播阻塞候选人。在AIM 2中，我们将开发新的统计方法 在异质性下估计多价疫苗的功效，并分析当前登革热疫苗的试验 候选人。在AIM 3中，我们将开发用于评估和比较一般替代物的统计方法 保护免于试验的集合。我们将使用这些方法探索候选人的一般代理 轮状病毒疫苗，我们将开发用于验证新保护的免疫相关的方法 脑膜炎球菌A疫苗。在AIM 4中，我们将开发方法来估计传染性疫苗功效 从两种级别聚类的研究中估算了流感疫苗的这一数量。我们将发展一个 风险的新度量称为潜在暴露并描述其特征。在AIM 5中，我们将开发两个 用于评估新候选结核病疫苗的新型设计。第一个是随机案例参考 设计将是评估大量人群中新的结核病疫苗的一种经济高效的方法。这 第二是一种考虑事先致敏的设计，并将允许区分 因原发性感染或重新激活而引起的疾病疫苗。我们的新型设计和分析方法将 对实施实际研究有直接的后果。结果将直接贡献 监管和公共卫生政策决策，并将“用作计算机模拟中的输入来探索 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（请参阅说明）： 准确评估疫苗的直接，间接，总和总体影响对于调节和 政策决策。这里提出的研究将对实施实际影响产生直接影响 评估当前可用疫苗和未来疫苗影响的研究，从而直接贡献 健康。结果也将用于计算机模拟最佳疫苗接种策略。