Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA.
Biostatistics & Research Decision Sciences, Merck & Co, Inc, North Wales, Pennsylvania, USA.
Clin Infect Dis. 2021 Oct 20;73(8):1540-1544. doi: 10.1093/cid/ciaa1863.
A large number of studies are being conducted to evaluate the efficacy and safety of candidate vaccines against coronavirus disease 2019 (COVID-19). Most phase 3 trials have adopted virologically confirmed symptomatic COVID-19 as the primary efficacy end point, although laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also of interest. In addition, it is important to evaluate the effect of vaccination on disease severity. To provide a full picture of vaccine efficacy and make efficient use of available data, we propose using SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19 as dual or triple primary end points. We demonstrate the advantages of this strategy through realistic simulation studies. Finally, we show how this approach can provide rigorous interim monitoring of the trials and efficient assessment of the durability of vaccine efficacy.
正在进行大量研究来评估针对 2019 年冠状病毒病（COVID-19）的候选疫苗的疗效和安全性。大多数 3 期试验都采用病毒学确诊的有症状 COVID-19 作为主要疗效终点，尽管实验室确诊的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）也很有意义。此外，评估疫苗对疾病严重程度的影响也很重要。为了全面评估疫苗的疗效并充分利用现有数据，我们建议将 SARS-CoV-2 感染、有症状 COVID-19 和重症 COVID-19 作为双重或三重主要终点。我们通过真实模拟研究证明了这种策略的优势。最后，我们展示了这种方法如何能够对试验进行严格的中期监测并有效地评估疫苗疗效的持久性。
