Objective: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use.
Methods: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r).
Results: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results.
Conclusions: In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
目的: 构建药物不良反应信号快速识别（RiADP）模型，为临床用药的风险管理和科学决策提供帮助。
方法: 在不相称性测定分析理论的基础上，结合频数法和贝叶斯法建立一种R语言环境下临床可用的RiADP模型，并通过国际医学用语词典（MedDRA）编码，实现模型参数的临床解读。以美国食品药品监督管理局实际监测数据为依据，利用建立的RiADP模型对拟用于2019冠状病毒病治疗的抗病毒药物洛匹那韦/利托那韦的肝毒性进行识别，从而对模型进行验证。
结果: 本研究提出的RiADP模型包括4个模型参数：药物不良反应信号信息标准值、经验贝叶斯几何均值、报告比值比和不良反应报告例数。通过R语言参数包“PhViD”可以实现模型参数的快速输出，MedDRA编码后可转化为临床术语，形成药物不良反应的临床解释报告。模型对洛匹那韦/利托那韦肝毒性的评估结果与最新研究报道匹配，证明模型结果可靠。
结论: 本研究在R语言环境下提出了一种基于上市后药物监测数据的不良反应信号快速识别方法，可以在突发公共卫生事件下实现目标药物不良反应的快速预警，为临床用药的风险管理和决策提供循证依据。