Randomized vaccine trials are used to assess vaccine efficacy and to characterize the durability of vaccine induced protection. If efficacy is demonstrated, the treatment of placebo volunteers becomes an issue. For COVID-19 vaccine trials, there is broad consensus that placebo volunteers should be offered a vaccine once efficacy has been established. This will likely lead to most placebo volunteers crossing over to the vaccine arm, thus complicating the assessment of long term durability. We show how to analyze durability following placebo crossover and demonstrate that the vaccine efficacy profile that would be observed in a placebo controlled trial is recoverable in a trial with placebo crossover. This result holds no matter when the crossover occurs and with no assumptions about the form of the efficacy profile. We only require that the vaccine efficacy profile applies to the newly vaccinated irrespective of the timing of vaccination. We develop different methods to estimate efficacy within the context of a proportional hazards regression model and explore via simulation the implications of placebo crossover for estimation of vaccine efficacy under different efficacy dynamics and study designs. We apply our methods to simulated COVID-19 vaccine trials with durable and waning vaccine efficacy and a total follow-up of two years.

翻译：使用随机的疫苗试验来评估疫苗的功效,并确定疫苗诱导保护的持久性。如果效果得到证明,对安慰剂志愿人员的治疗就成为一个问题。对于COVID-19疫苗试验来说,人们普遍一致认为,一旦效果确定,应给安慰剂志愿人员提供疫苗。这可能导致大多数安慰剂志愿人员进入疫苗手臂,从而使长期耐久性评估复杂化。我们展示了如何分析安慰剂交叉之后的耐久性,并表明在安慰剂控制试验中将观察到的疫苗功效简介可以在安慰剂交叉的试验中恢复。这种结果在交错时没有任何问题,对效果简介的形式也没有假设。我们只要求疫苗功效简介适用于新接种的疫苗,而不论接种的时机如何。我们制定不同的方法,在比例危险回归模型范围内估计功效,并通过模拟安慰剂交叉对不同功效动态和研究设计下估计疫苗功效的影响。我们采用的方法模拟具有耐用和消减疫苗功效的COVID-19疫苗试验,并全面跟踪两年。