Creation of an ustekinumab external control arm for Crohn's disease using electronic health records data: A pilot study

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...

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Bibliographic Details
Published in:PloS one 2023-03, Vol.18 (3), p.e0282267-e0282267
Main Authors: 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, Martini, Benjamin D
Format: Article
Language:English
Subjects:
Algorithms
Biology and Life Sciences
Clinical trials
Computer and Information Sciences
Crohn Disease - drug therapy
Crohn's disease
Crohns disease
Drug dosages
Drug therapy
Electronic Health Records
Electronic medical records
Electronic records
FDA approval
Humans
Inflammatory bowel disease
Informatics
Medical records
Medicine and Health Sciences
Methods
Missing data
Monoclonal antibodies
Patients
Physical Sciences
Pilot Projects
Prospective Studies
Remission
Research and Analysis Methods
Retrospective Studies
Robustness
Steroids
Structured data
Ustekinumab - therapeutic use
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0282267