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Simulation studies are commonly used to evaluate the performance of newly developed meta-analysis methods. For methodology that is developed for an aggregated data meta-analysis, researchers often resort to simulation of the aggregated data directly, instead of simulating individual participant data from which the aggregated data would be calculated in reality. Clearly, distributional characteristics of the aggregated data statistics may be derived from distributional assumptions of the underlying individual data, but they are often not made explicit in publications. This paper provides the distribution of the aggregated data statistics that were derived from a heteroscedastic mixed effects model for continuous individual data. As a result, we provide a procedure for directly simulating the aggregated data statistics. We also compare our distributional findings with other simulation approaches of aggregated data used in literature by describing their theoretical differences and by conducting a simulation study for three meta-analysis methods: DerSimonian and Laird's pooled estimate and the Trim & Fill and PET-PEESE method for adjustment of publication bias. We demonstrate that the choices of simulation model for aggregated data may have a relevant impact on (the conclusions of) the performance of the meta-analysis method. We recommend the use of multiple aggregated data simulation models for investigation of new methodology to determine sensitivity or otherwise make the individual participant data model explicit that would lead to the distributional choices of the aggregated data statistics used in the simulation., Comment: 26 pages, 6 tables

Copas' method corrects a pooled estimate from an aggregated data meta-analysis for publication bias. Its performance has been studied for one particular mechanism of publication bias. We show through simulations that Copas' method is not robust against other realistic mechanisms. This questions the usefulness of Copas' method, since publication bias mechanisms are typically unknown in practice., Comment: 1 Figure, 12 pages

Medical studies for chronic disease are often interested in the relation between longitudinal risk factor profiles and individuals' later life disease outcomes. These profiles may typically be subject to intermediate structural changes due to treatment or environmental influences. Analysis of such studies may be handled by the joint model framework. However, current joint modeling does not consider structural changes in the residual variability of the risk profile nor consider the influence of subject-specific residual variability on the time-to-event outcome. In the present paper, we extend the joint model framework to address these two heterogeneous intra-individual variabilities. A Bayesian approach is used to estimate the unknown parameters and simulation studies are conducted to investigate the performance of the method. The proposed joint model is applied to the Framingham Heart Study to investigate the influence of anti-hypertensive medication on the systolic blood pressure variability together with its effect on the risk of developing cardiovascular disease. We show that anti-hypertensive medication is associated with elevated systolic blood pressure variability and increased variability elevates risk of developing cardiovascular disease., Comment: 34 pages, 4 figures