随机试验是临床证据生成的黄金标准，但有时会受到不可行性和不清晰的真实世界应用的限制。外部对照组（ECA）研究可以通过构建回顾性队列，紧密模拟前瞻性队列，来帮助解决这些证据缺口。在罕见疾病或癌症之外构建这些队列的经验是有限的。我们使用电子健康记录（EHR）数据为Crohn’s病开发ECA的方法。我们在加州大学旧金山分校的EHR数据库中查询并手动筛选记录，以确定符合USTEKINUMAB参考组干预试验TRIDENT的资格标准的患者。我们定义了时间点以平衡缺失数据和偏差。我们比较了不同插补模型对队列成员和结果的影响。我们评估了算法数据维护的准确性与手动审查相比。最后，我们评估了USTEKINUMAB治疗后的疾病活动情况。筛选确认了183名患者。 30％的队列缺少基线数据。尽管如此，队列成员和结果对插补方法具有稳健性。使用结构化数据确定非症状基础的疾病活动元素的算法与手动审查相比准确。队列由56名患者组成，超过了TRIDENT计划的招募人数。34％的队列在第24周处于无类固醇缓解状态。我们使用信息学和手动方法结合另一种新方法，在Crohn’s病的EHR数据中探索了用于创建ECA的方法。但是，我们的研究揭示了当使用标准护理临床数据进行二次利用时，存在显着的缺失数据。需要更多的工作来改善试验设计与典型临床实践模式的对齐，从而为像Crohn’s病这样的慢性疾病启用更稳健的ECA。版权所有：© 2023 Rudrapatna et al.本文为开放获取文章，根据知识共享署名许可证分发，允许在任何媒体中自由使用、分发和复制，前提是原作者和来源得到了适当的认可。

Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn's disease using electronic health records (EHR) data.We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab.Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24.We piloted an approach for creating an ECA in Crohn's disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn's disease.Copyright: © 2023 Rudrapatna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.