仙灵骨葆制剂上市后临床安全性真实世界多维度研究设计

药品上市后临床安全性研究应开展真实世界的多维度设计,充分考虑多种来源的数据、证据及证据的整合。论文以仙灵骨葆制剂的上市后临床安全性研究设计为例,报告了国家不良反应监测中心自发呈报系统数据、医院信息系统数据、文献数据的统计分析以及数据、分析结果和证据的整合,通过证据整合发现:仙灵骨葆制剂的一般ADR主要是胃肠系统损害,表现为恶心、呕吐、口干、便秘、腹泻等;严重ADR主要表现为肝胆系统损害,表现为肝功能异常、肝酶升高、肝细胞损害等;过敏反应有时候表现为一般ADR,有时候表现为严重ADR;肝功能异常具有性别差异,女性比例偏高;肝功能异常出现3~7 d和15 d及以2个发病高峰,提示可能存在不同的发病机制;恶心、呕吐和胃功能紊乱是仙灵骨葆制剂的ADR预警信号。论文进一步讨论了回顾性数据对于前瞻性研究设计的支撑,初步明确了安全性真实世界多维度研究设计中主要数据源的优势和不足,从安全性证据的角度分析了数据之间的互补性和相应研究的时序性。

Real World Multi-dimensional Design of Clinical Safety Research on Xianling Gubao Preparation

The clinical safety research on post-marketing medicines should carry out the multi-dimensional design of the real world study,and fully consider the data,evidence from multiple sources,and fully consider the evidence integration.This paper reported the clinical safety research design of Xianling Gubao capsule,reported the analysis of spontaneous reporting system data,hospital information system data,and literature data.Through the integration of safety data and evidence,it was found that the general ADR of Xianling Gubao capsule is mainly gastrointestinal system damage,which is manifested as nausea,vomiting,dry mouth,constipation and diarrhea,etc.;serious ADR is mainly manifested in liver and gall system damage,which is manifested in liver function abnormality,liver enzyme elevation,liver cell damage,etc.;anaphylaxis is sometimes manifested in general ADR,sometimes in serious ADR;liver function abnormality has gender difference,and the proportion of women is on the high side;liver function abnormality occurs in 3~7 days,15 days and two peak periods,suggesting that there may be different pathogenesis.Nausea,vomiting and gastric dysfunction are the ADR warning signals of Xianling Gubao capsule.The paper further discussed the support of retrospective data for prospective research design,initially clarified the advantages and disadvantages of the main data sources in the security real world multi-dimensional research design,and analyzed the complementarity between the data and the timing of the corresponding research from the perspective of security evidence.