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Background: Drug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties (i.e., drug-host interaction). This concept is crucial for personalized drug safety but remains under-studied, primarily due to methodological challenges and limited data availability. By monitoring a large volume of adverse event reports in the postmarket stage, spontaneous adverse event reporting systems provide an unparalleled resource of information for adverse events and could be utilized to explore risk disparities of specific adverse events by age, sex, and other host factors. However, well-formulated statistical methods to formally address such risk disparities are currently lacking., Methods: In this paper, we present a statistical framework to explore spontaneous adverse event reporting databases for drug-host interactions and detect risk disparities in adverse drug events by various host factors, adapting methods for safety signal detection. We proposed four different methods, including likelihood ratio test, normal approximation test, and two tests using subgroup ratios. We applied our proposed methods to simulated data and Food and Drug Administration (FDA) Adverse Event Reporting Systems (FAERS) and explored sex-/age-disparities in reported liver events associated with specific drug classes., Results: The simulation result demonstrates that two tests (likelihood ratio, normal approximation) can detect disparities in adverse drug events associated with host factors while controlling the family wise error rate. Application to real data on drug liver toxicity shows that the proposed method can be used to detect drugs with unusually high level of disparity regarding a host factor (sex or age) for liver toxicity or to determine whether an adverse event demonstrates a significant unbalance regarding the host factor relative to other events for the drug., Conclusion: Though spontaneous adverse event reporting databases require careful data processing and inference, the sheer size of the databases with diverse data from different countries provides unique resources for exploring various questions for drug safety that are otherwise impossible to address. Our proposed methods can be used to facilitate future investigation on drug-host interactions in drug toxicity using a large number of reported adverse events., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)