Tan George S Q, Maro Judith C, Wang Shirley V, Toh Sengwee, Morton Jedidiah I, Ilomäki Jenni, Wong Jenna, Li Xiaojuan
Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Australia.
Baker Heart and Diabetes Institute, Melbourne, Australia.
Am J Epidemiol. 2024 Sep 11. doi: 10.1093/aje/kwae355.
Most drug repurposing studies using real-world data focused on validating, instead of generating, hypotheses. We used tree-based scan statistics to generate repurposing hypotheses for sodium-glucose cotransporter-2 inhibitors (SGLT2i). We used an active-comparator, new-user design to create a 1:1 propensity-score matched cohort of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) initiators in the MerativeTM MarketScan® Research Databases. Tree-based scan statistics were estimated across an ICD-10-CM-based hierarchical outcome tree using incident outcomes identified from hospital and outpatient diagnoses. We used an adjusted P≤0.01 as the threshold for statistical alert to prioritize associations for evaluation as repurposing signals. We varied the analyses by tree size, scanning level, and clinical settings for outcomes. There were 80,510 matched SGLT2i-DPP4i initiator pairs with 215,333 outcomes among SGLT2i initiators and 223,428 outcomes among DPP4i initiators. There were 18 prioritized associations, which included chronic kidney disease (P=0.0001), an expected signal, and anemia (P=0.0001). Heart failure (P=0.0167), another expected signal, was identified slightly beyond the statistical alert threshold. Narrowing the outcome tree, scanning at different tree levels, and including outcomes from different clinical settings influenced the scan statistics. We identified signals aligning with recently approved indications of SGLT2i, plus potential repurposing signals supported by existing evidence but requiring future validation.
大多数利用真实世界数据进行的药物重新利用研究侧重于验证假设，而非提出假设。我们使用基于树的扫描统计方法来生成钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）的重新利用假设。我们采用活性对照新用户设计，在默克多数据库（MerativeTM MarketScan® Research Databases）中创建了一个1:1倾向评分匹配队列，其中包括SGLT2i起始者和二肽基肽酶4抑制剂（DPP4i）起始者。基于国际疾病分类第十版临床修正版（ICD-10-CM）的分层结局树，利用从医院和门诊诊断中确定的发病结局，估计基于树的扫描统计量。我们将调整后的P≤0.01作为统计警报阈值，以优先评估关联作为重新利用信号。我们通过树的大小、扫描水平和结局的临床设置来改变分析。共有80,510对匹配的SGLT2i-DPP4i起始者对，SGLT2i起始者中有215,333个结局，DPP4i起始者中有223,428个结局。有18个优先关联，其中包括慢性肾脏病（P=0.0001），这是一个预期信号，以及贫血（P=0.0001）。另一个预期信号心力衰竭（P=0.0167），其识别略超出统计警报阈值。缩小结局树、在不同树级别进行扫描以及纳入不同临床设置的结局会影响扫描统计量。我们识别出与SGLT2i最近获批适应症相符的信号，以及现有证据支持但需要未来验证的潜在重新利用信号。
