Suttonand AJ, Higgins JPT (2008) Recent developments in meta-analysis. Sutton AJ, Kendrick D, Coupland CAC (2008) Meta-analysis of individual and aggregate-level data. Jones AP, Riley RD, Williamson PR, Whitehead A (2009) Meta-analysis of individual patient data versus aggregate data from longitudinal clinical trials. Peters JL, Mengersen KL (2008) Meta-analysis of repeated measures study designs. Ishak KJ, Platt RW, Joseph L, Hanley JA, Caro JJ (2007) Meta-analysis of longitudinal studies. Nam I, Mengersen K, Garthwaite P (2003) Multivariate meta-analysis. Houwelingen HCv, Arends LR, Stijnen T (2002) Advanced methods in meta-analysis: multivariate approach and meta-regression. Academic Press, New YorkĭerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Hedges LV, Olkin I (1985) Statistical methods for meta-analysis. Whitehead A (2002) Meta-analysis of controlled clinical trials. Piedbois P, Buyse M (2004) Meta-analyses based on abstracted data: a step in the right direction, but only a first step. Glass GV (1976) Primary, secondary and meta-analysis of research. Models that included only treatment arm-level random effects were not superior in any scenario. With regard to correctly characterizing the variability, models that accounted for correlation within a study and treatment arm over time were the best in some situations, while models that accounted for study-level correlation only were better in others.

With all estimation strategies, the fixed random effects parameters were accurately estimated.

We compared estimation models that included study and/or treatment arm-level random effects, with and without residual correlation. Simulation models that were linear and non-linear in the random effects were investigated. Using simulation, we explored and evaluated ways to implement multi-level random effects in NONMEM. As a result, model-based meta-analysis may require more than two levels of random effects to correctly characterize this correlation structure. Observations within a study are correlated because the patients come from a common population, and the mean observations over time within a treatment arm are correlated because they are based on the same set of patients. Literature data are often reported as multiple (longitudinal) mean outcomes observed in several groups of patients within a study.

Eta nonmem