目的: 利用真实世界医保结算数据,评价恩替卡韦（Entecavir,ETV）仿制药与原研药在延缓慢性乙型肝炎（CHB）病情进展方面的临床实效。方法: 引入关系图卷积网络（RGCN）与异构图注意力网络（HGT）技术,对诊疗行为进行规范性识别与药品规格归集;结合卡尔曼滤波算法量化患者处方依从性。采用倾向评分匹配（PSM）平衡基线特征,并利用Cox比例风险回归模型比较两组患者发生肝癌、肝衰竭及肝腹水等严重肝脏事件的风险差异。结果: 经算法控制偏倚和校正后,最终纳入1481例患者（仿制药组987例,原研药组494例）。Log-rank检验显示,两组在肝癌（P=0.097）、肝衰竭（P=0.165）及肝腹水（P=0.661）的发生率上均无统计学差异。Cox回归分析结果显示,仿制药组相对于原研药组的肝癌风险比（HR）为1.21（95%CI: 0.47-3.14）,肝衰竭HR为0.58（95%CI: 0.25-1.33）,肝腹水HR为1.13（95%CI: 0.73-1.75）,所有95%CI均包含1.0。结论: 医保结算数据经严格清洗,排除不规范用药和依从性干扰后,验证了ETV仿制药与原研药在控制肝脏硬终点事件方面没有呈现出显著差异的证据,结论稳健,为集采政策提供了真实世界等效性证据,也为“三医”联动提供了真实世界研究领域实践层面的可靠案例。
Abstract
Objective: This study utilized real-world medical insurance settlement data to conduct a comparative evaluation of the clinical efficacy of Entecavir (ETV) generic drugs and the original drugs in delaying disease progression in chronic hepatitis B (CHB). Methods: The study employed relational graph convolutional networks (RGCN) and heterogeneous graph attention (HGT) networks to standardize the identification of clinical behaviors and drug specifications, while employing the Kalman filtering algorithm to quantify patient prescription adherence. Propensity score matching (PSM) was used to balance baseline characteristics, and Cox proportional hazards regression models were applied to compare the risk differences between the two groups for severe liver events such as hepatocellular carcinoma (HCC), liver failure, and hepatic ascites. Results: After algorithmic bias control and correction, a total of 1481 patients were included (987 in the generic drug group and 494 in the original drug group). The Log-rank test revealed no statistically significant differences between the two groups in the incidence of HCC (P=0.097), liver failure (P=0.165), or hepatic ascites (P=0.661). Cox regression analysis demonstrated that the hazard ratio (HR) for HCC in the generic drug group was 1.21 (95% CI: 0.47-3.14), for liver failure HR was 0.58 (95% CI: 0.25-1.33), and for hepatic ascites HR was 1.13 (95% CI: 0.73-1.75), with all 95% CIs containing 1.0. Conclusion: After rigorous cleaning to exclude non-standard drug use and compliance-related confounders, there is no evidence of significant differences between ETV generic drugs and the original drugs in controlling hepatic hard-endpoint events, yielding robust and reliable conclusions. The findings provide real-world evidence of therapeutic equivalence to support the centralized drug procurement policy, as well as a reliable case study in the field of real-world research for coordinated development and regulation of medical insurance, medical services, and pharmaceuticals.
关键词
恩替卡韦 /
仿制药 /
一致性评价 /
原研药 /
临床实效比较 /
真实世界研究
Key words
Entecavir /
generic drug /
consistency evaluation /
original drug /
clinical efficacy comparison /
real-world study
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基金
徐州医疗保险研究会课题“基于医保结算时间序列特征提取的仿制药品实效对比评价方法研究——以恩替卡韦为例”（XYY2024-04）
