Meta-analysis of median survival times with inverse-variance weighting

Abstract: We consider the problem of meta-analyzing outcome measures based on median survival times, such as the difference of median survival times between groups. Primary studies with time-to-event outcomes often report estimates of median survival times and corresponding confidence intervals based on the Kaplan-Meier estimator. However, applying conventional inverse-variance weighted methods to meta-analyze outcome measures based on median survival is often challenging because within-study standard error estimates are typically not available in this setting. In this article, we consider an inverse-variance weighted approach to meta-analyze median survival times that estimates the within-study standard errors from the reported confidence intervals. We conduct a series of simulation studies evaluating the performance of this approach at the study level (i.e., for estimating the standard error of median survival) and the meta-analytic level (i.e., for estimating the pooled median, difference of medians, and ratio of medians). We find that this approach often performs comparable to a benchmark approach that uses the true within-study standard errors for meta-analyzing median-based outcome measures. We then illustrate an application of this approach in a meta-analysis evaluating survival benefits of being assigned to experimental arms versus comparator arms in randomized trials for non-small cell lung cancer therapies.