Avoiding biases when estimating effects of COVID-19 vaccination during immune checkpoint inhibitor therapy

SARS-CoV-2 mRNA vaccination (COVID-19 vaccination) within 100 days of immune checkpoint inhibitor (ICI) treatment was reported to improve survival and prevent disease progression in patients with non-small cell lung cancer (NSCLC) and metastatic melanoma (Grippin et al., Nature, 2025). However, the clinical evidence, derived from real-world observational data, suffers from methodological limitations. Specifically, the vaccinated and unvaccinated groups differed in subtle ways due to the timing of vaccination, the beginning of follow-up, and the definition of eligibility. These key limitations can be overcome by carefully conducting a target trial emulation analysis. Using the original data from Grippin et al., we emulated a target trial to estimate the causal effect of COVID-19 vaccination within 100 days of ICI initiation on overall survival and progression-free survival in patients with NSCLC and metastatic melanoma. In contrast to the original analysis, we found no evidence that COVID-19 vaccination improves survival outcomes in these populations.