Commonly, clinical trials report effects not only for the full study population but also for patient subgroups. Meta-analyses of subgroup-specific effects and treatment-by-subgroup interactions may be inconsistent, especially when trials apply different subgroup weightings. We show that meta-regression can, in principle, with a contribution adjustment, recover the same interaction inference regardless of whether interaction data or subgroup data are used. Our Bayesian framework for subgroup-data interaction meta-analysis inherently (i) adjusts for varying relative subgroup contribution, quantified by the information fraction (IF) within a trial; (ii) is robust to prevalence imbalance and variation; (iii) provides a self-contained, model-based approach; and (iv) can be used to incorporate prior information into interaction meta-analyses with few studies.The method is demonstrated using an example with as few as seven trials of disease-modifying therapies in relapsing-remitting multiple sclerosis. The Bayesian Contribution-adjusted Meta-analysis by Subgroup (CAMS) indicates a stronger treatment-by-disability interaction (relapse rate reduction) in patients with lower disability (EDSS <= 3.5) compared with the unadjusted model, while results for younger patients (age < 40 years) are unchanged.By controlling subgroup contribution while retaining subgroup interpretability, this approach enables reliable interaction decision-making when published subgroup data are available.Although the proposed CAMS approach is presented in a Bayesian context, it can also be implemented in frequentist or likelihood frameworks.
翻译:通常,临床试验不仅报告全研究人群的效应,还会报告患者亚组的效应。针对亚组特异性效应和治疗-亚组交互作用的元分析可能存在不一致性,尤其当试验采用不同的亚组权重时。我们证明,通过贡献度调整,元回归原则上能够恢复相同的交互作用推断,无论使用的是交互作用数据还是亚组数据。我们提出的亚组数据交互作用元分析贝叶斯框架具有以下内在特性:(i) 通过试验内的信息分数量化并调整不同相对亚组贡献度;(ii) 对患病率不平衡及变异具有稳健性;(iii) 提供自包含的基于模型的方法;(iv) 可用于在仅有少数研究的交互作用元分析中纳入先验信息。该方法通过一个仅包含七项复发缓解型多发性硬化疾病修饰疗法试验的案例进行演示。贝叶斯贡献调整亚组元分析表明,与未调整模型相比,在低残疾程度患者中观察到更强的治疗-残疾交互作用,而年轻患者的结果保持不变。通过控制亚组贡献度同时保持亚组可解释性,该方法能够在已发表亚组数据可用时实现可靠的交互作用决策。尽管提出的CAMS方法在贝叶斯框架中呈现,但同样可在频率主义或似然框架中实施。