Hauben Manfred
Pfizer Inc, New York, NY, USA.
Clin Ther. 2023 Feb;45(2):117-133. doi: 10.1016/j.clinthera.2023.01.002. Epub 2023 Jan 31.
Despite increasing mechanistic understanding, undetected and underrecognized drug-drug interactions (DDIs) persist. This elusiveness relates to an interwoven complexity of increasing polypharmacy, multiplex mechanistic pathways, and human biological individuality. This persistent elusiveness motivates development of artificial intelligence (AI)-based approaches to enhancing DDI detection and prediction capabilities. The literature is vast and roughly divided into "prediction" and "detection." The former relatively emphasizes biological and chemical knowledge bases, drug development, new drugs, and beneficial interactions, whereas the latter utilizes more traditional sources such as spontaneous reports, claims data, and electronic health records to detect novel adverse DDIs with authorized drugs. However, it is not a bright line, either nominally or in practice, and both are in scope for pharmacovigilance supporting signal detection but also signal refinement and evaluation, by providing data-based mechanistic arguments for/against DDI signals. The wide array of intricate and elegant methods has expanded the pharmacovigilance tool kit. How much they add to real prospective pharmacovigilance, reduce the public health impact of DDIs, and at what cost in terms of false alarms amplified by automation bias and its sequelae are open questions.
尽管对药物相互作用机制的理解不断加深,但未被发现和未得到充分认识的药物相互作用(DDIs)仍然存在。这种难以捉摸的情况与日益增加的联合用药复杂性、多重作用机制途径以及人类生物学个体差异交织在一起有关。这种持续存在的难以捉摸的情况促使人们开发基于人工智能(AI)的方法来提高药物相互作用的检测和预测能力。相关文献浩如烟海,大致可分为“预测”和“检测”两类。前者相对强调生物学和化学知识库、药物开发、新药以及有益的相互作用,而后者则利用更传统的数据源,如自发报告、索赔数据和电子健康记录,来检测已获批准药物之间新出现的不良药物相互作用。然而,无论是在名义上还是在实践中,这两者之间并没有明确的界限,而且它们在药物警戒中都发挥着作用,不仅支持信号检测,还通过提供基于数据的支持或反对药物相互作用信号的机制论据来进行信号细化和评估。各种各样复杂而精妙的方法扩展了药物警戒工具包。这些方法在多大程度上能真正用于前瞻性药物警戒、减少药物相互作用对公众健康的影响,以及以自动化偏差及其后果导致的误报为代价,这些都是悬而未决的问题。