Jeffrey G Klann1, Hossein Estiri1, Griffin M Weber2, Bertrand Moal3, Paul Avillach4, Chuan Hong4, Amelia L M Tan4, Brett K Beaulieu-Jones4, Victor Castro5, Thomas Maulhardt6, Alon Geva7,8, Alberto Malovini9, Andrew M South10, Shyam Visweswaran11, Michele Morris11, Malarkodi J Samayamuthu11, Gilbert S Omenn12, Kee Yuan Ngiam13, Kenneth D Mandl8, Martin Boeker6, Karen L Olson8, Danielle L Mowery14, Robert W Follett15, David A Hanauer16, Riccardo Bellazzi9,17, Jason H Moore14, Ne-Hooi Will Loh18, Douglas S Bell15, Kavishwar B Wagholikar19, Luca Chiovato9,20, Valentina Tibollo9, Siegbert Rieg21, Anthony L L J Li22, Vianney Jouhet23, Emily Schriver24, Zongqi Xia25, Meghan Hutch26, Yuan Luo26, Isaac S Kohane4, Gabriel A Brat4, Shawn N Murphy27,28. 1. Laboratory of Computer Science, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Biomedical Informatics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. 3. IAM Unit, Public Health Department , Bordeaux University Hospital, Bordeaux, France. 4. Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA. 5. Research Information Science and Computing, Mass General Brigham, Boston, Massachusetts, USA. 6. Institute of Medical Biometry and Statistics, Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 7. Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA. 8. Computational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts, USA. 9. Laboratory of Informatics and Systems Engineering for Clinical Research, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy. 10. Section of Nephrology, Department of Pediatrics, Brenner Children's Hospital, Wake Forest School of Medicine, Winston Salem, North Carolina, USA. 11. Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 12. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. 13. Department of Biomedical Informatics-WisDM, National University Health System, Singapore. 14. Department of Biostatistics, Epidemiology, and Informatics, Institute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 15. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. 16. Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA. 17. Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy. 18. Division of Critical Care, National University Health System, Singapore. 19. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. 20. Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy. 21. Division of Infectious Diseases, Department of Medicine II, Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 22. National Center for Infectious Diseases, Tan Tock Seng Hospital, Singapore. 23. ERIAS-INSERM U1219 BPH, Bordeaux University Hospital, Bordeaux, France. 24. Data Analytics Center, Penn Medicine, Philadelphia, Pennsylvania, USA. 25. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 26. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 27. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. 28. Research Information Science and Computing , Mass General Brigham, Boston, Massachusetts, USA.
Abstract
OBJECTIVE: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity. MATERIALS AND METHODS: Twelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site. RESULTS: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review. DISCUSSION: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions. CONCLUSIONS: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.
OBJECTIVE: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity. MATERIALS AND METHODS: Twelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site. RESULTS: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review. DISCUSSION: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions. CONCLUSIONS: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.
Authors: Johan H Thygesen; Christopher Tomlinson; Sam Hollings; Mehrdad A Mizani; Alex Handy; Ashley Akbari; Amitava Banerjee; Jennifer Cooper; Alvina G Lai; Kezhi Li; Bilal A Mateen; Naveed Sattar; Reecha Sofat; Ana Torralbo; Honghan Wu; Angela Wood; Jonathan A C Sterne; Christina Pagel; William N Whiteley; Cathie Sudlow; Harry Hemingway; Spiros Denaxas Journal: Lancet Digit Health Date: 2022-06-09
Authors: Maryam Khodaverdi; Bradley S Price; J Zachary Porterfield; H Timothy Bunnell; Michael T Vest; Alfred Jerrod Anzalone; Jeremy Harper; Wes D Kimble; Hamidreza Moradi; Brian Hendricks; Susan L Santangelo; Sally L Hodder Journal: JAMIA Open Date: 2022-07-09
Authors: Boyd M Knosp; Catherine K Craven; David A Dorr; Elmer V Bernstam; Thomas R Campion Journal: J Am Med Inform Assoc Date: 2022-03-15 Impact factor: 7.942
Authors: Griffin M Weber; Harrison G Zhang; Sehi L'Yi; Tianxi Cai; Andrew M South; Gabriel A Brat; Clara-Lea Bonzel; Chuan Hong; Paul Avillach; Alba Gutiérrez-Sacristán; Nathan P Palmer; Amelia Li Min Tan; Xuan Wang; William Yuan; Nils Gehlenborg; Anna Alloni; Danilo F Amendola; Antonio Bellasi; Riccardo Bellazzi; Michele Beraghi; Mauro Bucalo; Luca Chiovato; Kelly Cho; Arianna Dagliati; Hossein Estiri; Robert W Follett; Noelia García Barrio; David A Hanauer; Darren W Henderson; Yuk-Lam Ho; John H Holmes; Meghan R Hutch; Ramakanth Kavuluru; Katie Kirchoff; Jeffrey G Klann; Ashok K Krishnamurthy; Trang T Le; Molei Liu; Ne Hooi Will Loh; Sara Lozano-Zahonero; Yuan Luo; Sarah Maidlow; Adeline Makoudjou; Alberto Malovini; Marcelo Roberto Martins; Bertrand Moal; Michele Morris; Danielle L Mowery; Shawn N Murphy; Antoine Neuraz; Kee Yuan Ngiam; Marina P Okoshi; Gilbert S Omenn; Lav P Patel; Miguel Pedrera Jiménez; Robson A Prudente; Malarkodi Jebathilagam Samayamuthu; Fernando J Sanz Vidorreta; Emily R Schriver; Petra Schubert; Pablo Serrano Balazote; Byorn Wl Tan; Suzana E Tanni; Valentina Tibollo; Shyam Visweswaran; Kavishwar B Wagholikar; Zongqi Xia; Daniela Zöller; Isaac S Kohane Journal: J Med Internet Res Date: 2021-10-11 Impact factor: 7.076
Authors: Trang T Le; Alba Gutiérrez-Sacristán; Jiyeon Son; Chuan Hong; Andrew M South; Brett K Beaulieu-Jones; Ne Hooi Will Loh; Yuan Luo; Michele Morris; Kee Yuan Ngiam; Lav P Patel; Malarkodi J Samayamuthu; Emily Schriver; Amelia Lm Tan; Jason Moore; Tianxi Cai; Gilbert S Omenn; Paul Avillach; Isaac S Kohane; Shyam Visweswaran; Danielle L Mowery; Zongqi Xia Journal: medRxiv Date: 2021-01-29
Authors: Trang T Le; Alba Gutiérrez-Sacristán; Jiyeon Son; Chuan Hong; Andrew M South; Brett K Beaulieu-Jones; Ne Hooi Will Loh; Yuan Luo; Michele Morris; Kee Yuan Ngiam; Lav P Patel; Malarkodi J Samayamuthu; Emily Schriver; Amelia L M Tan; Jason Moore; Tianxi Cai; Gilbert S Omenn; Paul Avillach; Isaac S Kohane; Shyam Visweswaran; Danielle L Mowery; Zongqi Xia Journal: Sci Rep Date: 2021-10-12 Impact factor: 4.996
Authors: Jeffrey G Klann; Zachary H Strasser; Meghan R Hutch; Chris J Kennedy; Jayson S Marwaha; Michele Morris; Malarkodi Jebathilagam Samayamuthu; Ashley C Pfaff; Hossein Estiri; Andrew M South; Griffin M Weber; William Yuan; Paul Avillach; Kavishwar B Wagholikar; Yuan Luo; Gilbert S Omenn; Shyam Visweswaran; John H Holmes; Zongqi Xia; Gabriel A Brat; Shawn N Murphy Journal: medRxiv Date: 2022-02-18
Authors: Shyam Visweswaran; Malarkodi J Samayamuthu; Michele Morris; Griffin M Weber; Douglas MacFadden; Philip Trevvett; Jeffrey G Klann; Vivian S Gainer; Barbara Benoit; Shawn N Murphy; Lav Patel; Nebojsa Mirkovic; Yuliya Borovskiy; Robert D Johnson; Matthew C Wyatt; Amy Y Wang; Robert W Follett; Ngan Chau; Wenhong Zhu; Mark Abajian; Amy Chuang; Neil Bahroos; Phillip Reeder; Donglu Xie; Jennifer Cai; Elaina R Sendro; Robert D Toto; Gary S Firestein; Lee M Nadler; Steven E Reis Journal: JAMIA Open Date: 2021-04-19