Meta-analysis With Zero-event Studies: A Comparative Study With Application to COVID-19 Data

Abstract Background: Meta-analysis is a statistical method to synthesize evidence from a number of independent studies, including those from clinical studies with binary outcomes. In practice, when there are zero events in one or both groups, it may cause statistical problems in the subsequent analysis. Methods: In this paper, by considering the relative risk as the effect size, we conduct a comparative study that consists of four continuity correction methods and another state-of-the-art method without the continuity correction, namely the generalized linear mixed models. To further advance the literature, we also introduce a new method of the continuity correction for estimating the relative risk. Results: From the simulation studies, the new method performs well in terms of mean squared error when there are few studies. In contrast, the generalized linear mixed model performs the best when the number of studies is large. In addition, by reanalyzing a recent COVID-19 data, it is evident that the double-zero-event studies impact on the estimate of the mean effect size. Conclusion: We recommend the new method to handle the zero-event studies when there are only few studies in the meta-analysis, or instead use the GLMM when the number of studies is large. The double-zero-event study may beinformative, and so we suggest not excluding them.