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Network meta-analysis (NMA) is essential for clinical decision-making. NMA enables inference for all pair-wise comparisons between interventions available for the same indication, by using both direct evidence and indirect evidence. In randomized trials with time-to event outcome data, such as lung cancer data, conventional NMA methods rely on the hazard ratio and the proportional hazards assumption, and ignore the varying follow-up durations across trials. We introduce a novel multivariate NMA model for the difference in restricted mean survival times (RMST). Our model synthesizes all the available evidence from multiple time points simultaneously and borrows information across time points through within-study covariance and between-study covariance for the differences in RMST. We propose an estimator of the within-study covariance and we then assume it to be known. We estimate the model under the Bayesian framework. We evaluated our model by conducting a simulation study. Our multiple-time-point model yields lower mean squared error over the conventional single-time-point model at all time points, especially when the availability of evidence decreases. We illustrated the model on a network of randomized trials of second-line treatments of advanced non-small-cell lung cancer. Our multiple-time-point model yielded increased precision and detected evidence of benefit at earlier time points as compared to the single-time-point model. Our model has the advantage of providing clinically interpretable measures of treatment effects. [ABSTRACT FROM AUTHOR]

Meta-epidemiological studies are used to compare treatment effect estimates between randomized clinical trials with and without a characteristic of interest. To our knowledge, there is presently nothing to help researchers to a priori specify the required number of meta-analyses to be included in a meta-epidemiological study. We derived a theoretical power function and sample size formula in the framework of a hierarchical model that allows for variation in the impact of the characteristic between trials within a meta-analysis and between meta-analyses. A simulation study revealed that the theoretical function overestimated power (because of the assumption of equal weights for each trial within and between meta-analyses). We also propose a simulation approach that allows for relaxing the constraints used in the theoretical approach and is more accurate. We illustrate that the two variables that mostly influence power are the number of trials per meta-analysis and the proportion of trials with the characteristic of interest. We derived a closed-form power function and sample size formula for estimating the impact of trial characteristics in meta-epidemiological studies. Our analytical results can be used as a 'rule of thumb' for sample size calculation for a meta-epidemiologic study. A more accurate sample size can be derived with a simulation study. [ABSTRACT FROM AUTHOR]