Takeda Pharmaceuticals, 300 Massachusetts Ave, Cambridge, MA 02139, United States.
Sanofi, 50 Binney Street, Cambridge, MA 02142, United States.
Contemp Clin Trials. 2021 Jan;100:106225. doi: 10.1016/j.cct.2020.106225. Epub 2020 Nov 21.
In the past decades, the world has experienced several major virus outbreaks, e.g. West African Ebola outbreak, Zika virus in South America and most recently global coronavirus (COVID-19) pandemic. Many vaccines have been developed to prevent a variety of infectious diseases successfully. However, several infections have not been preventable so far, like COVID-19, which induces an immediate urgent need for effective vaccines. These emerging infectious diseases often pose unprecedent challenges for the global heath community as well as the conventional vaccine development paradigm. With a long and costly traditional vaccine development process, there are extensive needs in innovative vaccine trial designs and analyses, which aim to design more efficient vaccines trials. Featured with reduced development timeline, less resource consuming or improved estimate for the endpoints of interests, these more efficient trials bring effective medicine to target population in a faster and less costly way. In this paper, we will review a few vaccine trials equipped with adaptive design features, Bayesian designs that accommodate historical data borrowing, the master protocol strategy emerging during COVID-19 vaccine development, Real-World-Data (RWD) embedded trials and the correlate of protection framework and relevant research works. We will also discuss some statistical methodologies that improve the vaccine efficacy, safety and immunogenicity analyses. Innovative clinical trial designs and analyses, together with advanced research technologies and deeper understanding of the human immune system, are paving the way for the efficient development of new vaccines in the future.
在过去的几十年中，世界经历了几次重大的病毒爆发，例如西非埃博拉疫情、南美洲的寨卡病毒以及最近的全球冠状病毒（COVID-19）大流行。已经成功开发了许多疫苗来预防各种传染病。然而，到目前为止，仍有几种感染是无法预防的，例如 COVID-19，这立即引发了对有效疫苗的迫切需求。这些新出现的传染病经常给全球卫生界以及传统的疫苗开发模式带来前所未有的挑战。由于传统的疫苗开发过程漫长且成本高昂，因此在创新的疫苗试验设计和分析方面存在广泛的需求，旨在设计更有效的疫苗试验。这些更有效的试验具有缩短开发时间、减少资源消耗或改进感兴趣终点的估计等特点，它们以更快、更低成本的方式将有效的药物带给目标人群。在本文中，我们将回顾一些配备适应性设计功能、贝叶斯设计以适应历史数据借用、COVID-19 疫苗开发期间出现的主方案策略、嵌入式真实世界数据（RWD）试验以及保护相关性框架和相关研究工作的疫苗试验。我们还将讨论一些改进疫苗疗效、安全性和免疫原性分析的统计方法。创新的临床试验设计和分析，结合先进的研究技术和对人类免疫系统的深入了解，为未来新疫苗的高效开发铺平了道路。
