1. Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study
- Author
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Rudrapatna, Vivek A, Cheng, Yao-Wen, Feuille, Colin, Mosenia, Arman, Shih, Jonathan, Shi, Yongmei, Roberson, Olivia, Rubin, Benjamin, Butte, Atul J, Mahadevan, Uma, Skomrock, Nicholas, Erondu, Ngozi, Chehoud, Christel, Rahim, Saquib, Apfel, David, Curran, Mark, Khan, Najat S, O’Brien, Christopher, Terry, Natalie, and Martini, Benjamin D
- Subjects
Health Services and Systems ,Health Sciences ,Autoimmune Disease ,Digestive Diseases ,Machine Learning and Artificial Intelligence ,Networking and Information Technology R&D (NITRD) ,Clinical Research ,Patient Safety ,Generic health relevance ,Good Health and Well Being ,Humans ,Ustekinumab ,Crohn Disease ,Pilot Projects ,Electronic Health Records ,Prospective Studies ,Retrospective Studies ,General Science & Technology - Abstract
BackgroundRandomized 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.MethodsWe 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.ResultsScreening 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.ConclusionWe 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.
- Published
- 2023