Meta-analyses have become the gold standard for synthesizing evidence from multiple clinical trials, and they are especially useful when outcomes are rare or adverse since individual trials often lack sufficient power to detect a treatment effect. However, when zero events are observed in one or both treatment arms in a trial, commonly used…

The "LFK" index has been promoted as an improved method to detect bias in meta-analysis. Putatively, its performance does not depend on the number of studies in the meta-analysis. We conducted a simulation study, comparing the "LFK" index test to three standard tests for funnel plot asymmetry in settings with smaller or larger…

Background: Traditionally, meta-analysis of time-to-event outcomes reports a single pooled hazard ratio assuming proportional hazards (PH). For health technology assessment evaluations, hazard ratios are frequently extrapolated across a lifetime horizon. However, when treatment effects vary over time, an assumption of PH is not always valid. The…

Rare events meta-analyses of randomized controlled trials (RCTs) are often underpowered because the outcomes are infrequent. Real-world evidence (RWE) from non-randomized studies may provide valuable complementary evidence about the effects of rare events, and there is growing interest in including such evidence in the decision-making process.…

Meta-analyses are an important tool within systematic reviews to estimate the overall effect size and its confidence interval for an outcome of interest. If heterogeneity between the results of the relevant studies is anticipated, then a random-effects model is often preferred for analysis. In this model, a prediction interval for the true effect…

Meta-analyses based on systematic literature reviews are commonly used to obtain a quantitative summary of the available evidence on a given topic. However, the reliability of any meta-analysis is constrained by that of its constituent studies. One major limitation is the possibility of small-study effects, when estimates from smaller and larger…

The performance of statistical methods is often evaluated by means of simulation studies. In case of network meta-analysis of binary data, however, simulations are not currently available for many practically relevant settings. We perform a simulation study for sparse networks of trials under between-trial heterogeneity and including multi-arm…

Studies combined in a meta-analysis often have differences in their design and conduct that can lead to heterogeneous results. A random-effects model accounts for these differences in the underlying study effects, which includes a heterogeneity variance parameter. The DerSimonian-Laird method is often used to estimate the heterogeneity variance,…

Meta-analyses of clinical trials targeting rare events face particular challenges when the data lack adequate numbers of events for all treatment arms. Especially when the number of studies is low, standard random-effects meta-analysis methods can lead to serious distortions because of such data sparsity. To overcome this, we suggest the use of…

Research synthesis, eg, by meta-analysis, is more and more considered in the area of high-dimensional data from molecular research such as gene and protein expression data, especially because most studies and experiments are performed with very small sample sizes. In contrast to most clinical and epidemiological trials, raw data are often…

Random-effects meta-analysis methods include an estimate of between-study heterogeneity variance. We present a systematic review of simulation studies comparing the performance of different estimation methods for this parameter. We summarise the performance of methods in relation to estimation of heterogeneity and of the overall effect estimate,…

Meta-analyses are typically used to estimate the overall/mean of an outcome of interest. However, inference about between-study variability, which is typically modelled using a between-study variance parameter, is usually an additional aim. The DerSimonian and Laird method, currently widely used by default to estimate the between-study variance,…