Abstract
Large-scale deployment of safe and durably effective vaccines can curtail the COVID-19 pandemic.1−3 However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4−5 and thus does not pertain to long-term efficacy. To evaluate the duration of pro- tection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the per- formance of blinded and unblinded crossover designs in estimating long-term VE.
Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long‐term, open‐label safety study