Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study
<h4>Background</h4> 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 ret...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980824/?tool=EBI |
| _version_ | 1811159910742753280 |
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| author | Vivek A. Rudrapatna Yao-Wen Cheng Colin Feuille Arman Mosenia Jonathan Shih Yongmei Shi Olivia Roberson Benjamin Rubin Atul J. Butte Uma Mahadevan Nicholas Skomrock Ngozi Erondu Christel Chehoud Saquib Rahim David Apfel Mark Curran Najat S. Khan Christopher O’Brien Natalie Terry Benjamin D. Martini |
| author_facet | Vivek A. Rudrapatna Yao-Wen Cheng Colin Feuille Arman Mosenia Jonathan Shih Yongmei Shi Olivia Roberson Benjamin Rubin Atul J. Butte Uma Mahadevan Nicholas Skomrock Ngozi Erondu Christel Chehoud Saquib Rahim David Apfel Mark Curran Najat S. Khan Christopher O’Brien Natalie Terry Benjamin D. Martini |
| author_sort | Vivek A. Rudrapatna |
| collection | DOAJ |
| description | <h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusion</h4> 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. |
| first_indexed | 2024-04-10T05:48:40Z |
| format | Article |
| id | doaj.art-787eb227a93741be9dac7c3b645b88b1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T05:48:40Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-787eb227a93741be9dac7c3b645b88b12023-03-05T05:31:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01183Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot studyVivek A. RudrapatnaYao-Wen ChengColin FeuilleArman MoseniaJonathan ShihYongmei ShiOlivia RobersonBenjamin RubinAtul J. ButteUma MahadevanNicholas SkomrockNgozi EronduChristel ChehoudSaquib RahimDavid ApfelMark CurranNajat S. KhanChristopher O’BrienNatalie TerryBenjamin D. Martini<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusion</h4> 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980824/?tool=EBI |
| spellingShingle | Vivek A. Rudrapatna Yao-Wen Cheng Colin Feuille Arman Mosenia Jonathan Shih Yongmei Shi Olivia Roberson Benjamin Rubin Atul J. Butte Uma Mahadevan Nicholas Skomrock Ngozi Erondu Christel Chehoud Saquib Rahim David Apfel Mark Curran Najat S. Khan Christopher O’Brien Natalie Terry Benjamin D. Martini Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study PLoS ONE |
| title | Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study |
| title_full | Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study |
| title_fullStr | Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study |
| title_full_unstemmed | Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study |
| title_short | Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study |
| title_sort | creation of an ustekinumab external control arm for crohn s disease using electronic health records data a pilot study |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980824/?tool=EBI |
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