Jen Hsiao-Hsuan, Chang Wei-Jung, Lin Ting-Yu, Hsu Chen-Yang, Yen Amy Ming-Fang, Lai Chao-Chih, Chen Tony Hsiu-Hsi
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 533, No. 17, Xu-Zhou Road, Taipei, 100, Taiwan.
Master of Public Health Degree Program, National Taiwan University, Taipei, 100, Taiwan.
Infect Dis Ther. 2021 Jun;10(2):815-825. doi: 10.1007/s40121-021-00431-9. Epub 2021 Mar 18.
Efficient evaluation with an early surrogate endpoint, taking into account the process of disease evolution, may not only clarify inconsistent or underpowered results but also provide a new insight into the exploration of a new antiviral therapy for treating COVID-19 patients.
We assessed the dynamics of COVID-19 disease spectrum, commencing from low-risk (no or low oxygen supplement), medium-risk (non-invasive ventilator or high oxygen supplement), and high-risk (extracorporeal membrane oxygenation or invasive ventilator) risk state on enrollment, and then the subsequent progression and regression of risk states until discharge or death. The efficacy of antiviral therapy in altering the dynamics was assessed by using the high-risk state as a surrogate endpoint based on the data retrieved from the two-arm Adaptive Covid-19 Treatment Trial.
Using the high-risk state as a surrogate endpoint, remdesivir treatment led to a decrease in the high-risk COVID-19 state by 34.8% (95% CI 26.7-42.0%) for a 14-day period and 29.3% (95% CI 28.8-29.8%) up to 28 days, which were consistent with a statistically significant reduction of death by 30.5% (95% CI 6.6, 50.9%) up to a 28-day period. The estimates of numbers needed to be treated were 100.9 (95% CI 88.1, 115.7) for using the high-risk COVID-19 state as a surrogate endpoint for a 14-day period and 133.3 (95% CI 112.5, 158.0) were required for averting one death from COVID-19 up to 28 days.
We demonstrate the expedient use of the high-risk COVID-19 disease status as a surrogate endpoint for evaluating the primary outcome of the earliest death.
使用早期替代终点进行有效评估，并考虑疾病演变过程，不仅可以澄清不一致或效力不足的结果，还可以为探索治疗新冠肺炎患者的新抗病毒疗法提供新的见解。
我们评估了新冠肺炎疾病谱的动态变化，从入组时的低风险（无需或低氧补充）、中风险（无创通气或高氧补充）和高风险（体外膜肺氧合或有创通气）风险状态开始，然后是风险状态的后续进展和回归，直至出院或死亡。基于双臂自适应新冠肺炎治疗试验检索的数据，以高风险状态作为替代终点，评估抗病毒治疗改变动态变化的疗效。
以高风险状态作为替代终点，瑞德西韦治疗使高风险新冠肺炎状态在14天内下降了34.8%（95%CI 26.7-42.0%），在28天内下降了29.3%（95%CI 28.8-29.8%），这与在28天内死亡人数统计学显著减少30.5%（95%CI 6.6, 50.9%）一致。以高风险新冠肺炎状态作为14天替代终点时，所需治疗人数估计为100.9（95%CI 88.1, 115.7），在28天内避免一例新冠肺炎死亡需要133.3（95%CI 112.5, 158.0）。
我们证明了将高风险新冠肺炎疾病状态便捷地用作评估最早死亡这一主要结局的替代终点。
