基于文本信息的变态反应ADE主动监测关键技术研究及模块开发

发布时间：2018-03-28 14:21

本文选题：药物不良事件　切入点：主动监测　出处：《中国人民解放军医学院》2017年硕士论文

【摘要】：研究背景:药品不良反应(Adverse Drug Reaction,ADR )监测是药品安全性监测的主要手段,是药品上市后评价的重要组成部分。自动监测作为药品上市后安全性研究的新方法,具有良好的发展前景。解放军总医院团队研发的“医疗机构ADE主动监测与智能评估警示系统”在量化指标的自动监测方面取得了较好的成绩,但由于无法利用医疗电子档案中的非结构文本数据,监测项目受到局限,系统功能有待扩展。研究目的:本研究旨在开展基于文本信息的变态反应ADE主动监测关键技术研究及模块开发,并制订自动监测系统的规范化操作流程,扩展系统的应用范围,强化优质电子医疗病历资源的利用与药品安全性再评价研究。研究方法:(1)探索基于医疗文本信息的ADE自动监测技术,将变态反应模块分为皮肤类变态反应及过敏性休克两部分,通过建立特征词集、生成自然语言分析器、完成文本分类器的输出、模块测试等步骤,完成变态反应自动监测模块的开发。(2)结合前期工作基础,总结经验,梳理、制定自动监测系统规范化操作流程,绘制流程图,为多中心药物评价研究提供应用指导。(3)在上述研究的基础上,开展注射用盐酸罗沙替丁醋酸酯的安全性再评价自动监测实践,包括血小板减少、血红蛋白减少、白细胞减少、肝功能损害、肾功能损害、胰酶异常、皮肤类变态反应、过敏性休克、心律失常等9个方面ADR事件。研究结果:(1)开发完成变态反应监测模块符合“医疗机构ADE主动监测及智能评估警示系统”框架原则,基本实现了设计需求。并在随后变态反应模块测试过程中获得了 14042例注射用头孢曲松钠、13818例注射用尖吻蝮蛇血凝酶在真实世界的皮肤类变态反应发生率,分别为0.33%、0.065%,和11969丹参酮ⅡA磺酸钠注射液、11281例马来酸桂哌齐特注射液、25280例注射用头孢曲松钠的过敏性休克及过敏样反应的发生率,分别是 0.025%、0.018%、0.0079%。(2)制订了自动监测系统的规范化操作流程,并贯以详细的监测路线流程图。(3)完成9284例注射用盐酸罗沙替丁醋酸酯用药人群9种ADR主动监测与评价研究,发生率分别是:肝功能损害0.93%-1.04%,血红蛋白减少0.20%-0.23%,白细胞减少0.13%-0.15%,血小板减少0.11%-0.12%,肾功能损害0.28%,胰酶异常0.01%,皮肤类变态反应0.05%,心律失常0.08%;总体发生率1.79%( 95%CI: 1.62%-2.06%);过敏性休克病例0;表明该药在临床规范用药情况下的整体风险性较小,但用药时长、患者年龄等为ADR发生的危险因素,应予以关注。结论:开发完成变态反应监测模块采用的贝叶斯网络和决策树分类算法成熟,文本分类性能良好,能够满足药品安全性主动监测的的需要,特别是皮肤类变态反应模块的敏感度、准确度均达到了较高水平。自动监测流程的梳理为降低系统使用难度,保障研究成果质量的稳定性方面做出了贡献,并得到籍此开展的大样本真实世界药物安全评价研究的结果支持。
[Abstract]:Research background: adverse drug reactions (Adverse Drug, Reaction, ADR) is the main means of monitoring drug safety monitoring, is an important part of the postmarketing evaluation. As a new method for automatic monitoring of the safety of marketed medicines, with good prospects for development. The Liberation Army General Hospital Research Team "medical ADE active surveillance has achieved good results in the automatic monitoring of quantitative indicators and warning system of intelligent evaluation, but unable to use unstructured text data in electronic medical archives, monitoring project is limited, the system function to be extended. The purpose of this study was to carry out research on the key technology and the development of active monitoring module allergy ADE text based on the information, and to develop standardized automatic monitoring system operation process, expand the application range, strengthen the quality of electronic medical records and resources With the drug safety evaluation research. Research methods: (1) to explore the medical text information automatic monitoring technology based on ADE, the module is divided into two parts of allergic skin allergy and allergic shock, characterized by the establishment of a set of words that generate natural language parser, complete output text classifier, step test module so, complete allergy automatic monitoring module development. (2) based on previous work, sum up experience, combing, making the automatic monitoring system of standardized operation flow, flow chart, provide guidance for the evaluation of application of multi center drugs. (3) on the basis of the above research, and practice to carry out safety evaluation of automatic monitoring Roxatidine Acetate Hydrochloride For Injection, including thrombocytopenia, decreased hemoglobin, leukopenia, liver damage, kidney damage, abnormal skin allergy pancreatin, and anaphylactic shock, Arrhythmia in 9 aspects of ADR events. Results: (1) developed allergic reaction monitoring module in accordance with the "medical institutions ADE assessment of active monitoring and intelligent warning system" framework of principles, the basic realization of the design requirements. And obtained 14042 cases of Ceftriaxone Sodium for Injection in the subsequent testing of allergic reaction module, the incidence of 13818 cases in Haemocoagulase Agkistrodon for Injection the real world of skin allergy, were 0.33%, 0.065%, and 11969 of sodium tanshinone A sulfonate injection, 11281 cases of Cinepazide Maleate Injection, the incidence of anaphylaxis and anaphylactoid reaction in 25280 cases of Ceftriaxone Sodium for Injection, respectively is 0.025%, 0.018%, 0.0079%. (2) developed a standardized automatic monitoring system operation process and through a detailed flow chart of monitoring line. (3) 9284 cases completed with hydrochloric acid injection of roxatidine acetate medication group 9 ADR Active monitoring and evaluation, the incidence of liver damage were: 0.93%-1.04%, decreased hemoglobin 0.20%-0.23%, leukopenia 0.13%-0.15% thrombocytopenic 0.11%-0.12%, 0.28% renal dysfunction, abnormal trypsin 0.01%, skin allergy 0.05%, arrhythmia in 0.08%; the overall incidence rate of 1.79% (95%CI: 1.62%-2.06%); 0 cases showed allergic shock; the drug in the clinical standard medication case of overall risk is small, but the medication duration, patient age and other risk factors of ADR, which should be paid more attention. Conclusion: the completion of the development of Bayesian networks and decision tree classification of variable state reaction monitoring module adopts the mature algorithm, text classification performance is good, can satisfy the needs of the drug active safety monitoring, especially the skin allergy module sensitivity and accuracy have reached a high level. The automatic monitoring processes in order to reduce system We have made contributions to the difficulty of using, ensuring the stability of the quality of the research results, and supported the results of the large sample real world drug safety evaluation carried out.

【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R95

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