Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Drug Saf. 2020 Jun;43(6):567-582. doi: 10.1007/s40264-020-00915-6.
When a new drug or biologic product enters the market, its full spectrum of side effects is not yet fully understood, as use in the real world often uncovers nuances not suggested within the relatively narrow confines of preapproval preclinical and trial work.
We describe a new, phenome-wide association study (PheWAS)- and evidence-based approach for detection of potential adverse drug effects.
We leveraged our established platform, which integrates human genetic data with associated phenotypes in electronic health records from 29,722 patients of European ancestry, to identify gene-phenotype associations that may represent known safety issues. We examined PheWAS data and the published literature for 16 genes, each of which encodes a protein targeted by at least one drug or biologic product.
Initial data demonstrated that our novel approach (safety ascertainment using PheWAS [SA-PheWAS]) can replicate published safety information across multiple drug classes, with validated findings for 13 of 16 gene-drug class pairs.
By connecting and integrating in vivo and in silico data, SA-PheWAS offers an opportunity to supplement current methods for predicting or confirming safety signals associated with therapeutic agents.
当一种新的药物或生物制品进入市场时，其所有副作用尚未完全被理解，因为在真实世界中的使用通常会揭示出预批准的临床前和试验工作中相对狭窄范围内未提示的细微差别。
我们描述了一种新的、基于表型组关联研究（PheWAS）和基于证据的方法，用于检测潜在的药物不良反应。
我们利用我们现有的平台，该平台将人类遗传数据与来自 29722 名欧洲血统患者的电子健康记录中的相关表型整合在一起，以识别可能代表已知安全问题的基因-表型关联。我们检查了 16 个基因的 PheWAS 数据和已发表的文献，每个基因编码至少一种药物或生物制品靶向的蛋白质。
初步数据表明，我们的新方法（使用 PheWAS 进行安全性确定[SA-PheWAS]）可以在多个药物类别中复制已发表的安全性信息，对于 16 个基因-药物类别对中的 13 对有验证的发现。
通过连接和整合体内和体外数据，SA-PheWAS 为预测或确认与治疗剂相关的安全信号提供了一种机会，补充了当前的方法。
