A Bayesian dose-response meta-analysis model: simulation study and application

Dose-response models express the effect of different dose or exposure levels on a specific outcome. In meta-analysis, where aggregated-level data is available, dose-response evidence is synthesized using either one-stage or two-stage models in a frequentist setting. We propose a hierarchical dose-response model implemented in a Bayesian framework. We present the model with cubic dose-response shapes for a dichotomous outcome and take into account heterogeneity due to variability in the dose-response shape. We develop our Bayesian model assuming normal or binomial likelihood and accounting for exposures grouped in clusters. We implement these models in R using JAGS and we compare our approach to the one-stage dose-response meta-analysis model in a simulation study. We found that the Bayesian dose-response model with binomial likelihood has slightly lower bias than the Bayesian model with the normal likelihood and the frequentist one-stage model. However, all three models perform very well and give practically identical results. We also re-analyze the data from 60 randomized controlled trials (15,984 participants) examining the efficacy (response) of various doses of antidepressant drugs. All models suggest that the dose-response curve increases between zero dose and 40 mg of fluoxetine-equivalent dose, and thereafter is constant. We draw the same conclusion when we take into account the fact that five different antidepressants have been studied in the included trials. We show that implementation of the hierarchical model in Bayesian framework has similar performance to, but overcomes some of the limitations of the frequentist approaches and offers maximum flexibility to accommodate features of the data.