临床干预措施效力-效果差距弥合的方法学研究进展(一):改善真实世界研究的效果估计  

Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions(1):to improve the validity of real-world evidence

作　　者：刘佐相 龙子临 杨智荣 石舒原 许欣然 赵厚宇 杨祖耀[5] 符祝 宋海波 林腾飞 詹思延[1,2,10] 孙凤 Liu Zuoxiang;Long Zilin;Yang Zhirong;Shi Shuyuan;Xu Xinran;Zhao Houyu;Yang Zuyao;Fu Zhu;Song Haibo;Lin Tengfei;Zhan Siyan;Sun Feng(Department of Epidemiology and Biostatistics,School of Public Health,Peking University,Beijing 100191,China;Key Laboratory of Epidemiology of Major Diseases(Peking University),Ministry of Education,Beijing 100191,China;School of Computer Science and Control Engineering,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;China Rehabilitation Science Institute,China Disability Control and Prevention Center,China Disable Persons'Federation,Beijing 100068,China;School of Public Health and Primary Care,the Chinese University of Hong Kong,Hong Kong 999077,China;Administration of Hainan Boao Lecheng International Medical Tourism Pilot Zone,Hainan Institute of Real World Data,Haikou 571437,China;Department of Traditional Chinese Medicine Monitoring and Evaluation,Center for Drug Reevalaution,National Medical Products Administration,Beijing 100076,China;Key Laboratory for Research and Evaluation of Pharmacovigilance,National Medical Products Administration,Beijing 100076,China;Biomedical Information Technology Research Center,Institute of Advanced Computing and Digital Engineering,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;Clinical Epidemiology Research Center,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]重大疾病流行病学教育部重点实验室(北京大学),北京100191 [3]中国科学院深圳先进技术研究院计算机科学与控制工程学院,深圳518055 [4]中国康复科学所/中国残疾人联合会残疾预防与控制中心,北京100068 [5]香港中文大学公共卫生及基层医疗学院,中国香港999077 [6]海南省博鳌乐城国际医疗旅游先行区管理局,海南省真实世界数据研究院,海口571437 [7]国家药品监督管理局药品评价中心中药监测和评价部,北京100076 [8]国家药品监督管理局药物警戒研究与评价重点实验室,北京100076 [9]中国科学院深圳先进技术研究院先进计算与数字工程研究所生物医学信息技术研究中心,深圳518055 [10]北京大学第三医院临床流行病学研究中心,北京100191

出　　处：《中华流行病学杂志》2024年第2期286-293,共8页Chinese Journal of Epidemiology

基　　金：国家自然科学基金(72074011);中国药品监管科学行动计划第二批重点项目([2021]37-10);海南省博鳌乐城国际医疗旅游先行区管理局真实世界研究专项计划(HNLC2022RWS012)。

摘　　要：目的干预措施在临床实践中的实际干预效果与随机对照试验(RCT)中表现的效力存在差异,即效力-效果差距。RCT结果与真实世界研究(RWS)结果的差异可能无法代表真实的效力-效果差距,这是因为当RWS与RCT在研究设计上有较大差异,或RWS结果估计存在偏倚时,效力-效果的估计可能是有偏的。其次,当发现干预措施存在效力-效果差距,不能对所有患者实行一刀切的临床决策,而需要进一步评估影响干预措施效果的真实世界因素,识别可能取得期望效用的患者群体。方法检索PubMed、Embase、Web of Science、万方数据知识服务平台、维普数据库、中国知网6个数据库从建库至2022年12月31日的中英文文献,采用概括性综述的方法,对如何改进RWS设计从而弥合效力-效果差距的方法进行归纳整合和定性描述。结果共纳入10篇文献,探讨如何以RCT研究方案为模板,制定相应的RWS方案,在正确估计效力-效果差距的基础上,进一步评估干预措施在患者亚群中的效果,选取能获得预期收益风险比的患者亚群,从而弥合效力-效果差距。结论使用医疗大数据,模拟目标试验方案关键特征,可以提高研究结果的真实性和有效性,弥合效力-效果差距。Objective Differences between randomized controlled trial(RCT)results and real world study(RWS)results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation.Secondly,when there is an efficacyeffectiveness gap,it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods Six databases(PubMed,Embase,Web of Science,CNKI,Wanfang Data,and VIP)were searched up to 31st December 2022 with detailed search strategies.A scoping review method was used to integrate and qualitatively describe the included literature inductively.Results Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol.Moreover,based on correctly estimating the efficacy-effectiveness gap,evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

关 键 词：随机对照试验 真实世界证据 目标试验 效力 效果 

分 类 号：R195.1[医药卫生—卫生统计学]