Multivariate meta-analysis model for the difference in restricted mean survival times.

In randomized controlled trials (RCTs) with time-to-event outcomes, the difference in restricted mean survival times (RMSTD) offers an absolute measure of the treatment effect on the time scale. Computation of the RMSTD relies on the choice of a time horizon, $\tau$. In a meta-analysis, varying follow-up durations may lead to the exclusion of RCTs with follow-up shorter than $\tau$. We introduce an individual patient data multivariate meta-analysis model for RMSTD estimated at multiple time horizons. We derived the within-trial covariance for the RMSTD enabling the synthesis of all data by borrowing strength from multiple time points. In a simulation study covering 60 scenarios, we compared the statistical performance of the proposed method to that of two univariate meta-analysis models, based on available data at each time point and based on predictions from flexible parametric models. Our multivariate model yields smaller mean squared error over univariate methods at all time points. We illustrate the method with a meta-analysis of five RCTs comparing transcatheter aortic valve replacement (TAVR) with surgical replacement in patients with aortic stenosis. Over 12, 24, and 36 months of follow-up, those treated by TAVR live 0.28 [95% confidence interval (CI) 0.01 to 0.56], 0.46 (95% CI $-$0.08 to 1.01), and 0.79 (95% CI $-$0.43 to 2.02) months longer on average compared to those treated by surgery, respectively.