The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), US National Institutes of Health, US Department of Veterans Affairs, the Health Department from the Generalitat de Catalunya with a grant for research projects on SARS-CoV-2 and COVID-19 disease organized by the Direcció General de Recerca i Innovació en Salut, Janssen Research & Development, and IQVIA. The University of Oxford received funding related to this work from the Bill & Melinda Gates Foundation (Investment ID INV-016201 and INV-019257). This study was supported by National Key Research & Development Program of China (Project No.2018YFC0116901). OHSU received support from Gates Foundation, INV-016910 and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002369. The University of Washington received a grant related to this work from the Bill & Melinda Gates Foundation (INV-016910). No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, Department of Veterans Affairs or the United States Government, NHS, National Institute for Health and Care Excellence (NICE) or the Department of Health, England.
All the data partners received Institutional Review Board (IRB) approval or exemption. STARR-OMOP had approval from IRB Panel #8 (RB-53248) registered to Leland Stanford Junior University under the Stanford Human Research Protection Program (HRPP). The use of VA data was reviewed by the Department of Veterans Affairs Central IRB, was determined to meet the criteria for exemption under Exemption Category 4(3), and approved for Waiver of HIPAA Authorization. The research was approved by the Columbia University Institutional Review Board as an OHDSI network study. The use of SIDIAP was approved by the Clinical Research Ethics Committee of the IDIAPJGol (project code: 20/070-PCV). The use of HMAR was approved by the Parc de Salut Mar Clinical Research Ethics Committee. The use of CPRD was approved by the Independent Scientific Advisory Committee (ISAC) (protocol number 20_059RA2). This study is approved by the University of Florida IRB under protocol IRB202100175. Some databases used (HealthVerity, Premier, IQVIA Open Claims, Optum EHR, and Optum SES) in these analyses are commercially available, syndicated data assets that are licensed by contributing authors for observational research. These assets are de-identified commercially available data products that could be purchased and licensed by any researcher. The collection and de-identification of these data assets is a process that is commercial intellectual property and not privileged to the data licensees and the co-authors on this study. Licensees of these data have signed Data Use Agreements with the data vendors which detail the usage protocols for running retrospective research on these databases. All analyses performed in this study were in accordance with Data Use Agreement terms as specified by the data owners. As these data are deemed commercial assets, there is no Institutional Review Board applicable to the usage and dissemination of these result sets or required registration of the protocol with additional ethics oversight. Compliance with Data Use Agreement terms, which stipulate how these data can be used and for what purpose, is sufficient for the licensing commercial entities. Further inquiry related to the governance oversight of these assets can be made with the respective commercial entities: HealthVerity (healthverity.com), Premier (premierinc.com), IQVIA (iqvia.com) and Optum (optum.com). At no point in the course of this study were the authors of this study exposed to identified patient-level data. All result sets represent aggregate, de-identified data that are represented at a minimum cell size of >5 to reduce potential for re-identification. Furthermore, the New England Institutional Review Board of Janssen Research & Development (Raritan, NJ) has determined that studies conducted on licensed copies of Premier, Optum EHR, Optum SES and HealthVerity are exempt from study-specific IRB review, as these studies do not qualify as human subjects research.
Competing interest statement
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare:
Ms. Kostka is an employee of IQVIA. Mr. Sena is an employee and holds stock at Janssen Research & Development, a Johnson and Johnson family of companies. Dr. Golozar reports personal fees from Regeneron Pharmaceuticals, outside the submitted work. She is a full-time employee at Regeneron Pharmaceuticals. This work was not conducted at Regeneron Pharmaceuticals. Dr. Nyberg reports other funding from AstraZeneca, outside the submitted work. Dr. Wilcox reports grants from Bill and Melinda Gates Foundation, grants from National Institute of Health, during the conduct of the study Mr. Andryc is an employee of Janssen Research & Development, a subsidiary of Johnson & Johnson. Dr. Reich is an employee of IQVIA. Dr. Blacketer reports she is an employee and holds stock at Janssen Research & Development, a Johnson and Johnson family of companies. Dr. Morales is supported by a Wellcome Trust Clinical Research Development Fellowship (Grant 214588/Z/18/Z) and reports grants from Chief Scientist Office (CSO), grants from Health Data Research UK (HDR-UK), grants from National Institute of Health Research (NIHR), outside the submitted work. Mr. DeFalco reports he is an employee and holds stock at Janssen Research & Development, a Johnson and Johnson family of companies. Jason Thomas reports grants from Bill and Melinda Gates Foundation, grants from National Institute of Health, during the conduct of the study. Dr. Posada reports grants from National Library of Medicine, during the conduct of the study. Dr. Natarajan reports grants from US NIH, during the conduct of the study. Dr. Matheny reports grants from US NIH, grants from US VA HSR&D, during the conduct of the study. Dr. Weiskopf reports personal fees from Merck, outside the submitted work. Dr. Shah reports grants from National Library of Medicine, during the conduct of the study. Dr. Park reports grants from Ministry of Trade, Industry & Energy, Republic of Korea, grants from Ministry of Health & Welfare, Republic of Korea, grants from Bill & Melinda Gates Foundation, during the conduct of the study. Ms. Seager is an employee of IQVIA. Dr. DuVall reports grants from Anolinx, LLC, grants from Astellas Pharma, Inc, grants from AstraZeneca Pharmaceuticals LP, grants from Boehringer Ingelheim International GmbH, grants from Celgene Corporation, grants from Eli Lilly and Company, grants from Genentech Inc., grants from Genomic Health, Inc., grants from Gilead Sciences Inc., grants from GlaxoSmithKline PLC, grants from Innocrin Pharmaceuticals Inc., grants from Janssen Pharmaceuticals, Inc., grants from Kantar Health, grants from Myriad Genetic Laboratories, Inc., grants from Novartis International AG, grants from Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work. Dr. Fortin is an employee of Janssen R&D, a subsidiary of Johnson and Johnson. Dr. Vignesh reports grants from State of Arizona; Arizona Board of Regents, during the conduct of the study; grants from National Science Foundation, grants from Agency for Healthcare Research and Quality, grants from National Institutes of Health, outside the submitted work; .Dr. Subbian reports grants from State of Arizona; Arizona Board of Regents, during the conduct of the study; grants from National Science Foundation, grants from Agency for Healthcare Research and Quality, grants from National Institutes of Health, outside the submitted work. Dr. Rijnbeek reports grants from Innovative Medicines Initiative, from Janssen Research and Development, during the conduct of the study. Dr. Hripcsak reports grants from US NIH, during the conduct of the study. Dr. Ryan reports and is employee of Janssen Research and Development and shareholder of Johnson & Johnson. Dr. Suchard reports grants from US National Institutes of Health, grants from Department of Veterans Affairs, during the conduct of the study; grants from IQVIA, personal fees from Janssen Research and Development, grants from US Food and Drug Administration, personal fees from Private Health Management, outside the submitted work. Dr. Prieto-Alhambra reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants.
The views expressed are those of the authors and do not necessarily represent the views or policy of the Department of Veterans Affairs or the United States Government. No other relationships or activities that could appear to have influenced the submitted work.
Lead authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
KK, TDS, APU, AGS, AP, LL, PC, EB, VH, FN, SK, JK, AG, MAS, PR, GH, MS, AO, SD, MM, LMS, OA, CA, HA, KaS, WurA, JMB, NV, GdM, TMA, PJR, DPA contributed to the conceptualization and design of the study. KK, TDS, APU, AGS, AP, LL, PC, EB, VH, FN, SK, AG, MAS, PR, GH, MS, AO, SD, MM, LMS, NV, GdM, PJR, DPA contributed to the analysis phase of the study. KK, TDS, APU, AGS, AP, PC, SFB, EB, JAT, ABW, SK, PR, GH, TF, KN, AA, SF, NS, JoP, AW, KL, WC, CB, FD, CR, SGY, JyP, RWP, SS, CYJ, HZ, LiL, MG, YG, YZ, PJR, DPA, DavidD, RS, NW, XH, TM, CH, GL, JB, YanG are data owners and contribute to the extract-transform-load of their data to the OMOP CDM and the analytical execution of the study package within their local environments. KK, TDS, APU, AGS, AP, LL, PC, EB, SK, MR, ER, AG, JK, MAS, PR, GH, DD, VS, TMA, EHT, EM, MAS, PJR, DPA were critical to drafting the manuscript and the overall interpreting results.
We would like to acknowledge the patients who suffered from or died of this devastating disease, and their families and caregivers. We would also like to thank the social workers and healthcare professionals involved in the management of COVID-19 during these challenging times, from primary care to intensive care units.
Data sharing statement
Analyses were performed locally in compliance with all applicable data privacy laws. Although the underlying identified patient data is not readily available to be shared, authors contributing to this paper have direct access to the data sources used in this study. All results (e.g. aggregate statistics, not presented at a patient-level with redactions for minimum cell count) are available for public inquiry. These results are inclusive of site-identifiers by contributing data sources to enable interrogation of each contributing site. All analytic code and result sets are made available at: https://github.com/ohdsi-studies/Covid19CharacterizationCharybdis