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

Introduction: 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. Areas covered: 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 (n = 3) have attempted to address the issue of overlapping drug administration times. Expert opinion: 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.