Hypothesis-free screening of large administrative databases for unsuspected drug-outcome associations
Hypothesis-free screening of large administrative databases for unsuspected drug-outcome associations
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DOI：
10.1007/s10654-018-0386-8
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发表时间：
2018-06-01
影响因子：
13.6
通讯作者：
Pottegard, Anton
中科院分区：
文献类型：
--
作者：
Hallas, Jesper;Wang, Shirley V.;Pottegard, Anton
通过将流行病学技术应用于大型行政数据库，可以对未知或未被怀疑的药物不良反应进行积极监测。与传统设计相比，自我控制设计，如对称设计，在调整随时间稳定的混杂因素方面具有优势。这篇文章的目的是描述一个大型数据集的综合开放对称性分析的输出。对丹麦1995-2012年期间所有1950年前出生的人的所有药物分配和所有二级护理接触者进行了对称设计分析。我们分析了研究期间发生的所有药物-药物序列和所有药物-疾病序列。根据可能归因于暴露的结果的数量对已确定的关联进行了排名。在主要分析中，包括29,891,212例偶发药物治疗和21,300,000例偶发诊断。在主要分析中测试的186,758个关联中，43,575个(23.3%)显示出有意义的效应大小。在前200个药物-药物关联中，47%代表未知的关联，24%代表已知的药物不良反应，30%通过相互指示或反向因果关系解释。在排名前200位的药物-疾病协会中，这一比例分别为31%、15%和55%。如果结合信号的系统性后评估，通过对称性分析进行筛选可能是系统药物警戒活动的一个有用的起点。
Active surveillance for unknown or unsuspected adverse drug effects may be carried out by applying epidemiological techniques to large administrative databases. Self-controlled designs, like the symmetry design, have the advantage over conventional design of adjusting for confounders that are stable over time. The aim of this paper was to describe the output of a comprehensive open-ended symmetry analysis of a large dataset. All drug dispensings and all secondary care contacts in Denmark during the period 1995-2012 for persons born before 1950 were analyzed by a symmetry design. We analyzed all drug-drug sequences and all drug-disease sequences occurring during the study period. The identified associations were ranked according to the number of outcomes that potentially could be attributed to the exposure. In the main analysis, 29,891,212 incident drug therapies, and 21,300,000 incident diagnoses were included. Out of 186,758 associations tested in the main analysis, 43,575 (23.3%) showed meaningful effect size. For the top 200 drug-drug associations, 47% represented unknown associations, 24% represented known adverse drug reactions, 30% were explained by mutual indication or reverse causation. For the top 200 drug-disease associations the proportions were 31, 15, and 55%, respectively. Screening by symmetry analysis can be a useful starting point for systematic pharmacovigilance activities if coupled with a systematic post-hoc review of signals.