Bodner Korryn, Wang Linwei, Kustra Rafal, Kwong Jeffrey C, Sander Beate, Sbihi Hind, Irvine Michael A, Mishra Sharmistha
MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Nat Commun. 2025 May 24;16(1):4849. doi: 10.1038/s41467-025-59768-1.
Observational studies are essential for measuring vaccine effectiveness. Recent research has raised concerns about how a relationship between testing and vaccination may affect estimates of vaccine effectiveness against symptomatic infection (symptomatic VE). Using an agent-based network model and SARS-CoV-2 as an example, we investigated how differences in the likelihood of testing by vaccination could influence estimates of symptomatic VE across two common study designs: retrospective cohort and test-negative designs. First, we measured the influence of unequal testing on symptomatic VE estimates across study designs and sampling periods. Next, we investigated whether the magnitude of bias in VE estimates from unequal testing was shaped by immune escape (vaccine efficacy against susceptibility and against infectiousness) and underlying epidemic potential (probability of transmission). We found that unequal testing led to larger bias in the cohort design than the test-negative design and that bias was largest with lower efficacy against susceptibility. We also found the magnitude of bias was moderated by the study's selected sampling period, efficacy against infectiousness, and probability of transmission, with these moderating effects more pronounced in the test-negative design. Our study illustrates that VE estimates across study designs require careful interpretation, especially in the presence of epidemic and immunological heterogeneity.
观察性研究对于衡量疫苗有效性至关重要。最近的研究引发了人们对检测与疫苗接种之间的关系如何影响针对有症状感染的疫苗有效性（有症状疫苗效力）估计值的担忧。以基于主体的网络模型和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）为例，我们研究了按疫苗接种划分的检测可能性差异如何在两种常见研究设计中影响有症状疫苗效力的估计值：回顾性队列研究和检测阴性设计。首先，我们衡量了不平等检测对不同研究设计和抽样期间有症状疫苗效力估计值的影响。接下来，我们调查了不平等检测导致的疫苗效力估计值偏差幅度是否受免疫逃逸（疫苗针对易感性和传染性的效力）和潜在流行潜力（传播概率）的影响。我们发现，不平等检测在队列研究设计中导致的偏差比检测阴性设计更大，且在针对易感性效力较低时偏差最大。我们还发现，偏差幅度受研究选定的抽样期间、针对传染性的效力和传播概率的调节，这些调节效应在检测阴性设计中更为明显。我们的研究表明，不同研究设计中的疫苗效力估计值需要仔细解读，尤其是在存在流行和免疫异质性的情况下。
