Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index

Joseph T. King Jr.; James S. Yoon; Christopher T. Rentsch; Janet P. Tate; Lesley S. Park; Farah Kidwai-Khan; Melissa Skanderson; Ronald G. Hauser; Daniel A. Jacobson; Joseph Erdos; Kelly Cho; Rachel Ramoni; David R. Gagnon; Amy C. Justice

doi:10.1371/journal.pone.0241825

Peer Review History

Original SubmissionSeptember 1, 2020
8 Oct 2020 Decision Letter - Muhammad Adrish, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-20-27401 Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: the Veterans Health Administration COVID-19 (VACO) Index PLOS ONE Dear Dr. Justice, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== Please review comments made by the reviewers. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. In your ethics statement in the Methods section and in the online submission form, please provide additional information about the data used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether an IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. 3. Please include the date(s) on which you accessed the databases or records to obtain the data used in your study. 4. Please provide a table of relevant baseline characteristics of the subjects. 5. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 6. One of the noted authors is a group or consortium; VA-DOE COVID-19 Collaboration. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. 7. Please include a separate caption for each figure in your manuscript. 8. Please include a copy of Tables 1, 2 and 3 which you refer to in your text on pages 9, 10 and 11. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The study is interesting, well conducted and presented. I have only the following minor suggestions. Results Pag 9, lines 179-182. Please specify the two comparison groups (development cohort versus both validation cohorts combined?) Pag 9, Line 184 use the term “univariate” instead of “bivariate”. Pag 10, line 209. Please describe Figure 4 separately from Figure 3 and specify which subgroups were considered. Discussion Pag 11, line 234. Please delete Table 3. Pag. 13, line 262. Please mention that over estimation was particularly evident in the late validation cohort. Pag. 14. In the conclusion, please mention the necessity to validate the algorithm using other external cohorts. Tables were not included in the Manuscript. Reviewer #2: A rigorously executed and clearly argued study that makes excellent use of VA data resources and quantitative methods. Well done splitting data into test and validation subsets and explicitly referencing STROBE elements. The VA has several frailty/comorbidity indexes available, and it might be interesting to compare VACO to those (e.g. JEN Frailty Index, VA Frailty Index) as well but not an obstacle to acceptance of manuscript. The full data was not made available, but this is typical for patient data, and the authors mention VA's process for obtaining authorization to access the data. The authors did make an effort to provide the data they are able to provide, in the supplementary files. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Cristina Bosetti Reviewer #2: Yes:** Alex Bokov, Ph.D. [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0241825.r001
Revision 1
9 Oct 2020 Author Response Also contained in cover letter. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf We have updated the manuscript to ensure that it meets PLOS ONE’s style requirements. 2. In your ethics statement in the Methods section and in the online submission form, please provide additional information about the data used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether an IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. We have updated our Methods section and online submission form to reflect that the IRB approved a waiver of consent. (line 126) 3. Please include the date(s) on which you accessed the databases or records to obtain the data used in your study. We now state in our Methods that we accessed the VA databases on August 19, 2020. (line 103) 4. Please provide a table of relevant baseline characteristics of the subjects. Table 1 details the baseline characteristics of subjects in the development cohort and the validation cohorts. 5. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. The United States Department of Veterans Affairs (VA) places legal restrictions on access to veteran’s health care data, which includes both identifying data and sensitive patient information. The analytic data sets used for this study are not permitted to leave the VA firewall without a Data Use Agreement. This limitation is consistent with other studies based on VA data. However, VA data are made freely available to researchers behind the VA firewall with an approved VA study protocol. For more information, please visit https://www.virec.research.va.gov or contact the VA Information Resource Center (VIReC) at VIReC@va.gov. 6. One of the noted authors is a group or consortium; VA-DOE COVID-19 Collaboration. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. We have dropped the VA-DOE COVID-19 Collaboration from the author list. The Collaboration is satisfied with the recognition of specific members in the author list. 7. Please include a separate caption for each figure in your manuscript. We now include a separate caption for each figure in the manuscript. 8. Please include a copy of Tables 1, 2 and 3 which you refer to in your text on pages 9, 10 and 11. We now include Tables 1, 2, and 3 in the manuscript. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: No 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The study is interesting, well conducted and presented. I have only the following minor suggestions. Results Pag 9, lines 179-182. Please specify the two comparison groups (development cohort versus both validation cohorts combined?) The current text specifies that we are comparing the development and combine validation cohorts: “The development cohort was older (median age: 64.8 vs 62.3), with a higher proportion of non-Hispanic Blacks (52% vs 38%), and a lower proportion of males (93% vs 90%) than the combined validation cohorts (Table 1).” (underline emphasis added; lines 179-181) Pag 9, Line 184 use the term “univariate” instead of “bivariate”. We have changed “Bivariate” to “Univariate.” (line 197) Pag 10, line 209. Please describe Figure 4 separately from Figure 3 and specify which subgroups were considered. We now discuss Figure 3 and 4 in separate sentences. The sentence for Figure 3 specifies the we are comparing the development, early, and late validation cohorts. (lines 239-242) The revised sentence for Figure 4 specifies that we are comparing the validation and combined validation cohorts: “The VACO index demonstrated stable performance between the development and combined validation cohorts across sex, race/ethnicity, and geographic region subgroups (Figure 4).” (lines 242-244) Discussion Pag 11, line 234. Please delete Table 3. We have deleted the reference to Table 3. (line 295) Pag. 13, line 262. Please mention that over estimation was particularly evident in the late validation cohort. We now specify that over estimation was particularly evident in the late validation cohort. (line 323) Pag. 14. In the conclusion, please mention the necessity to validate the algorithm using other external cohorts. In the Conclusion, we now state: “We have demonstrated internal generalizability of the VACO Index within the VA - we recommend further validation in external datasets before applying the VACO Index outside of the VA.” (lines 353-355) Tables were not included in the Manuscript. We now include Tables 1, 2 and 3 with the manuscript. Reviewer #2: A rigorously executed and clearly argued study that makes excellent use of VA data resources and quantitative methods. Well done splitting data into test and validation subsets and explicitly referencing STROBE elements. The VA has several frailty/comorbidity indexes available, and it might be interesting to compare VACO to those (e.g. JEN Frailty Index, VA Frailty Index) as well but not an obstacle to acceptance of manuscript. In future work we hope to compare the VACO Index to other indices, but these comparisons are beyond the scope of this paper. The full data was not made available, but this is typical for patient data, and the authors mention VA's process for obtaining authorization to access the data. The authors did make an effort to provide the data they are able to provide, in the supplementary files. 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. We agree to publishing the peer review history of our article. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Cristina Bosetti Reviewer #2: Yes: Alex Bokov, Ph.D. [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0241825.r002
22 Oct 2020 Decision Letter - Muhammad Adrish, Editor Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index PONE-D-20-27401R1 Dear Dr. Justice, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Muhammad Adrish Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The author have addressed all my previous requests. The manuscript can threfore be accepted in the present form. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No https://doi.org/10.1371/journal.pone.0241825.r003
Formally Accepted
3 Nov 2020 Acceptance Letter - Muhammad Adrish, Editor PONE-D-20-27401R1 Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index Dear Dr. Justice: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Muhammad Adrish Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0241825.r004

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