Exploring the impact of co-exposure timing on drug-drug interactions in signal detection through spontaneous reporting system databases: a scoping review

Drug-drug interactions (DDIs) are defined as the pharmacological effects produced by the concomitant administration of two or more drugs. To minimize false positive signals and ensure their validity when analyzing Spontaneous Reporting System (SRS) databases, it has been suggested to incorporate key pharmacological principles, such as temporal plausibility. The scoping review of the literature was completed using MEDLINE from inception to March 2023. Included studies had to provide detailed methods for identifying DDIs in SRS databases. Any methodological approach and adverse event were accepted. Descriptive analyzes were excluded as we focused on automatic signal detection methods. The result is an overview of all the available methods for DDI signal detection in SRS databases, with a specific focus on the evaluation of the co-exposure time of the interacting drugs. It is worth noting that only a limited number of studies (<i>n</i> = 3) have attempted to address the issue of overlapping drug administration times. Current guidelines for signal validation focus on factors like the number of reports and temporal association, but they lack guidance on addressing overlapping drug administration times, highlighting a need for further research and method development.

药物相互作用（drug-drug interactions，DDIs）被定义为两种及以上药物联合给药时产生的药理学效应。为在分析自发呈报系统（spontaneous reporting system，SRS）数据库时最大限度降低假阳性信号并确保结果有效性，有研究建议纳入关键药理学原则，例如时间合理性。本研究依托MEDLINE数据库，对建库至2023年3月的相关文献完成了范围综述。纳入的研究需提供在SRS数据库中识别DDIs的详细方法，所有方法学方案与不良事件均符合收录标准。因本研究聚焦自动信号检测方法，描述性分析被排除在外。本综述的结果为当前SRS数据库中DDI信号检测的所有可用方法提供了全景概览，其中特别聚焦于相互作用药物的联合暴露时间评估。值得注意的是，仅有少量研究（<i>n</i> = 3）尝试探讨药物给药时间重叠的相关问题。当前的信号验证指南主要聚焦报告数量、时间关联性等因素，但未针对给药时间重叠问题提供相关指导，这凸显出进一步开展研究与方法开发的必要性。