Cargando…

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

BACKGROUND: 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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980824/
https://www.ncbi.nlm.nih.gov/pubmed/36862717
http://dx.doi.org/10.1371/journal.pone.0282267
_version_ 1784899973408620544
author 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.
author_facet 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.
author_sort Rudrapatna, Vivek A.
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
format Online
Article
Text
id pubmed-9980824
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-99808242023-03-03 Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study 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. PLoS One Research Article BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Public Library of Science 2023-03-02 /pmc/articles/PMC9980824/ /pubmed/36862717 http://dx.doi.org/10.1371/journal.pone.0282267 Text en © 2023 Rudrapatna et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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.
Creation of an ustekinumab external control arm for Crohn’s disease using electronic health records data: A pilot study
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980824/
https://www.ncbi.nlm.nih.gov/pubmed/36862717
http://dx.doi.org/10.1371/journal.pone.0282267
work_keys_str_mv AT rudrapatnaviveka creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT chengyaowen creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT feuillecolin creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT moseniaarman creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT shihjonathan creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT shiyongmei creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT robersonolivia creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT rubinbenjamin creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT butteatulj creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT mahadevanuma creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT skomrocknicholas creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT erondungozi creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT chehoudchristel creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT rahimsaquib creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT apfeldavid creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT curranmark creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT khannajats creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT obrienchristopher creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT terrynatalie creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy
AT martinibenjamind creationofanustekinumabexternalcontrolarmforcrohnsdiseaseusingelectronichealthrecordsdataapilotstudy