Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
Epidemiology Unit, German Rheumatism Research Centre Berlin, An institute of the Leibniz Association, Berlin, Germany.
Res Synth Methods. 2024 Nov;15(6):978-987. doi: 10.1002/jrsm.1748. Epub 2024 Aug 13.
In sparse data meta-analyses (with few trials or zero events), conventional methods may distort results. Although better-performing one-stage methods have become available in recent years, their implementation remains limited in practice. This study examines the impact of using conventional methods compared to one-stage models by re-analysing meta-analyses from the Cochrane Database of Systematic Reviews in scenarios with zero event trials and few trials. For each scenario, we computed one-stage methods (Generalised linear mixed model [GLMM], Beta-binomial model [BBM], Bayesian binomial-normal hierarchical model using a weakly informative prior [BNHM-WIP]) and compared them with conventional methods (Peto-Odds-ratio [PETO], DerSimonian-Laird method [DL] for zero event trials; DL, Paule-Mandel [PM], Restricted maximum likelihood [REML] method for few trials). While all methods showed similar treatment effect estimates, substantial variability in statistical precision emerged. Conventional methods generally resulted in smaller confidence intervals (CIs) compared to one-stage models in the zero event situation. In the few trials scenario, the CI lengths were widest for the BBM on average and significance often changed compared to the PM and REML, despite the relatively wide CIs of the latter. In agreement with simulations and guidelines for meta-analyses with zero event trials, our results suggest that one-stage models are preferable. The best model can be either selected based on the data situation or, using a method that can be used in various situations. In the few trial situation, using BBM and additionally PM or REML for sensitivity analyses appears reasonable when conservative results are desired. Overall, our results encourage careful method selection.
在稀疏数据荟萃分析(试验少或零事件)中,传统方法可能会扭曲结果。尽管近年来出现了性能更好的单阶段方法,但在实践中其应用仍然有限。本研究通过重新分析 Cochrane 系统评价数据库中的荟萃分析,在零事件试验和试验少的情况下,考察了使用传统方法与单阶段模型的结果差异。对于每种情况,我们计算了单阶段方法(广义线性混合模型 [GLMM]、贝塔二项式模型 [BBM]、使用弱信息先验的贝叶斯二项式-正态层次模型 [BNHM-WIP]),并将其与传统方法(零事件试验的 Peto-Odds 比 [PETO]、DerSimonian-Laird 方法 [DL];试验少的情况的 DL、Paule-Mandel [PM]、受限最大似然 [REML] 方法)进行比较。虽然所有方法都显示出相似的治疗效果估计,但统计精度存在显著差异。在零事件情况下,传统方法通常比单阶段模型产生更小的置信区间(CI)。在试验少的情况下,BBM 的 CI 长度平均最宽,与 PM 和 REML 相比,尽管后者的 CI 相对较宽,但通常会改变显著性。与零事件试验荟萃分析的模拟和指南一致,我们的结果表明单阶段模型更可取。可以根据数据情况选择最佳模型,或者使用可以在各种情况下使用的方法。在试验少的情况下,如果需要保守的结果,则使用 BBM 并另外进行 PM 或 REML 的敏感性分析似乎是合理的。总体而言,我们的结果鼓励谨慎选择方法。