Combating the SARS-CoV2 pandemic will require the fast development of effective preventive vaccines. Regulatory agencies may open accelerated approval pathways for vaccines if an immunological marker can be established as a mediator of a vaccine's protection. A rich source of information for identifying such correlates are large-scale efficacy trials of COVID-19 vaccines, where immune responses are measured subject to a case-cohort sampling design. We propose two approaches to estimation of mediation parameters in the context of case-cohort sampling designs. We establish the theoretical large-sample efficiency of our proposed estimators and evaluate them in a realistic simulation to understand whether they can be employed in the analysis of COVID-19 vaccine efficacy trials.
翻译:防治SARS-COV2大流行需要迅速发展有效的预防性疫苗。如果能够确定免疫标记作为疫苗保护的调解者,监管机构可以开辟加速批准疫苗的途径。确定这种关联的丰富信息来源是大规模试验COVID-19疫苗,根据个案分组抽样设计衡量免疫反应。我们建议两种办法,在个案分组抽样设计中估计调解参数。我们确定我们提议的估算员的理论大样本效率,并在现实的模拟中评估这些测试,以了解它们是否能够用于分析COVID-19疫苗功效试验。