论文标题
贝叶斯剂量反应荟萃分析模型:模拟研究和应用
A Bayesian dose-response meta-analysis model: simulation study and application
论文作者
论文摘要
剂量反应模型表达了不同剂量或暴露水平对特定结果的影响。在可用汇总数据的荟萃分析中,在频繁设置中,使用一个阶段或两阶段模型合成剂量反应证据。我们提出了在贝叶斯框架中实现的分层剂量响应模型。我们以立方剂量反应形状为二分法结果呈现模型,并考虑到剂量反应形状可变性而导致的异质性。我们开发假设正常或二项式的可能性并考虑将簇中的暴露的情况发生的,我们开发了贝叶斯模型。我们使用JAG在R中实施了这些模型,并将我们的方法与模拟研究中的一阶段剂量响应荟萃分析模型进行了比较。我们发现,具有二项式可能性的贝叶斯剂量反应模型的偏差略低于具有正常可能性和频繁主义的单阶段模型的贝叶斯模型。但是,这三个模型的表现都很好,并且实际上给出了相同的结果。我们还重新分析了60项随机对照试验(15,984名参与者)的数据,检查了各种剂量抗抑郁药的功效(反应)。所有模型都表明,剂量反应曲线在零剂量和40 mg氟西汀等效剂量之间增加,此后是恒定的。当我们考虑到在纳入的试验中研究了五种不同的抗抑郁药的事实时,我们得出相同的结论。我们表明,贝叶斯框架中层次模型的实现与性能相似,但克服了频繁方法的某些局限性,并提供了最大的灵活性以适应数据的功能。
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.