应用Hill准则评价培美曲塞心血管不良事件信号的因果关系

目的：评价培美曲塞与心血管系统信号的因果关系，为临床用药提供参考。方法：计算机检索主要的中英文数据库及美国国立医学图书馆临床试验注册中心，采用Hill准则对纳入的临床试验、个案报告以及美国不良事件报告系统（AERS）数据库相关信息进行分析评价。结果：共纳入10个符合条件的Ⅲ期临床试验，4例个案报告以及AERS数据库中132例患者，通过Hill准则分析发现，除了联系的强度较弱、剂量-反应关系不明确外，培美曲塞与心血管系统信号的因果关系满足了Hill准则可重复性、时序性、特异性、合理性、一致性、试验证据和可类比性7个方面。结论：培美曲塞与心血管系统信号存在因果关联的可能性较大，是可能的信号，临床应用需警惕该类信号并进一步监测。

Application of the Hill criteria to assess the causality of pemetrexed-induced cardiovascular system signals

OBJECTIVE To evaluate the causal relationship between pemetrexed and cardiovascular system signals and provide reference for clinical medication.METHODS The main Chinese and English databases and the National Library of Medicine Clinical Trial Registry were searched by computer. Hill criteria were used to analyze and evaluate the included clinical trials, case reports and relevant information of AERS database.RESULTS A total of 10 eligible phase Ⅲ clinical trials, 4 case reports, and 132 patients in the AERS database were included, and analysis by Hill criteria revealed that in addition to the weak strength of the link and the unclear dose-response relationship, the causal relationship between pemetrexed and cardiovascular system signals met seven aspects: Hill criteria reproducibility, timing, specificity, rationality, consistency, trial evidence, and comparability.CONCLUSION It is possible that pemetrexed is causally related to cardiovascular system signals and is a possible signal, which should be cautious and further monitored in clinical application.