Clinical trials: The mathematics of falling vaccine efficacy with rising disease incidence.
Clinical trials: The mathematics of falling vaccine efficacy with rising disease incidence.
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DOI：
10.1016/j.vaccine.2016.04.065
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发表时间：
2016-06-08
期刊：
影响因子：
5.5
通讯作者：
Lalloo DG
中科院分区：
文献类型：
--
作者：
Gomes MGM;Gordon SB;Lalloo DG
根据世界不同地区的随机对照试验估计，疫苗效力存在无法解释的差异，这在文献中屡见不鲜[1-4]。此外，在关注的疾病发病率较高的环境中测量疫苗效力时，有一个一致的趋势，即疫苗效力较低，这导致了对综合估计是否适当的质疑。在这里，我们研究了这种趋势的数学基础，并提出了一种跨设置有效的功效度量。该方法依赖于将指定病原体暴露和宿主反应的机制模型与按当地疾病发病率分层的全球疫苗试验数据拟合。这种模型能够估计每次接触病原体时疫苗的保护作用。一项估计暴露前疫苗效力的战略将能够更准确地估计各种疾病发病率的疫苗效力[b]。
Reports of unexplained discrepancies in the efficacy of vaccines, as estimated from randomised controlled trials in different parts of the world, are commonplace in the literature [1–4]. Moreover, there is a consistent trend for lower vaccine efficacy when measured in settings where the disease of interest has a higher incidence, leading to questions about the appropriateness of pooled estimates. Here, we examine the mathematical basis for such trends and propose a measure of efficacy that is valid across settings. The approach relies on fitting mechanistic models, which specify pathogen exposures and host responses, to global vaccine trial data stratified by local disease incidence. Such models enable the estimation of vaccine protection per exposure to the pathogen. A strategy to estimate per-exposure vaccine efficacy will enable more accurate estimates of vaccine efficacy across a range of disease incidence [5].
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