Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review

Samantha S. R. Crossfield; Lana Yin Hui Lai; Sarah R. Kingsbury; Paul Baxter; Owen Johnson; Philip G. Conaghan; Mar Pujades-Rodriguez

doi:10.1371/journal.pone.0224272

Peer Review History

Original SubmissionAugust 14, 2019
24 Sep 2019 Decision Letter - Michael Nurmohamed, Editor PONE-D-19-22874 Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review PLOS ONE Dear dr Crossfield, 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. In addition to the comments of the reviewers, please explain the added value of this manuscript to the field. We would appreciate receiving your revised manuscript by Nov 08 2019 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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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: Partly 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: Yes ****** 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: Interesting study/SR of gout studies Major issue: 1-1977 preliminary criteria by Wallace are too old and only able to classify tophaceous patients; One should at least do a study into newer criteria sets such as the 2015 ACR/EULAR criteria and/or Janssens'calculator as indeed making correct diagnoses in crystal induced arthritis is a world wde issue. 2- paper is missing focus of diagnostic or therapeutic issues in world literature on gout, as both are a challenge Reviewer #2: A very clear and sound study, addressing the variation in methods, results, reporting and bias risks in EHR-based gout studies . Recommendations to improve studies using EHR-systems are described. Therefore the study answers the study questions. I have no additional remarks. ****** 6. 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Revision 1
1 Oct 2019 Author Response Thank you to the Reviewers and for the opportunity to clarify our manuscript. We offer the below response to the comments and questions raised and detail the associated amendments made in the manuscript. References are given below to the associated line changes in the ‘Revised Manuscript with Track Changes.doc’ version of the manuscript. “In addition to the comments of the reviewers, please explain the added value of this manuscript to the field” The use of electronic health records (EHRs) in care management is becoming ubiquitous in many countries and secondary data use in research is correspondingly increasing. This systematic review provides evidence of the rise in EHR-based publications examining gout medication (Supplementary Figure 1). The added value of our in-depth evaluation of EHR-based studies relies on the fact that, in this rapidly growing and relatively novel research area, there is wide variation in the methods applied to conduct research as well as the quality of reporting and risk of bias and that this variation might affect the study results. This manuscript represents the first comprehensive assessment of this variation and of the impact that the methods chosen might have on the results obtained. This assessment was performed through a systematic review of articles reporting findings from studies based on the analysis of EHRs from patients, which were conducted to investigate the management of a common chronic disease, gout (amendments made to lines 76-96 to clarify this point). For example, we showed that by using a more specific disease definition to ascertain patients with gout, the likelihood of reporting that appropriate gout medication was prescribed to patients was increased. The systematic review highlights that there is large scope for improvement of reporting findings from EHR-based studies and quantified the wide variation in the comprehensiveness of reporting, with 73% of published studies discussing the limitations of EHR data use for research, and 5% reporting on key steps of EHR data preparation that can affect the findings. The observed gradual increase in the comprehensiveness of reporting over time is discussed with specific recommendations given for further improvements in future EHR-based studies. The review also reveals the limitations derived from applying current risk of bias assessment tools to EHR-based studies and discusses EHR-relevant biases that are not considered in these tools. It lists recommendations for future assessments of the reporting of, and of evaluations of risk of bias for, EHR-based studies (Table 4). These findings and recommendations, while derived from a review of gout pharmacotherapy studies, are applicable more widely to other EHR-based studies of prevalence, treatment, quality of management and patient outcomes (amendments made to lines 356-357, 366, 417-420, 433-445 to reflect this). Finally, the manuscript highlights strengths and limitations of EHR-based data in evaluating routine clinical management. It details the impact of the disease definition applied and the capacity to determine the effectiveness of medication in real world settings. In gout, EHR-based studies have been able to show the effectiveness and safety of urate-lowering therapy and their persistently suboptimal use across 1977 to 2017 in terms of low initiation, limited up-titration and low adherence (amendments made to lines to 382-387 emphasise this). Reviewer 1 Comment 1: “1977 preliminary criteria by Wallace are too old and only able to classify tophaceous patients; One should at least do a study into newer criteria sets such as the 2015 ACR/EULAR criteria and/or Janssens’calculator as indeed making correct diagnoses in crystal induced arthritis is a world wide issue.” We agree with the comment of the reviewer. The reference has accordingly been amended to the 2015 American College of Rheumatology / European League Against Rheumatism (ACR / EULAR) criteria (lines 127-128), which is used by several studies included in the systematic review. A recommendation has been added to advise that study disease definitions should reflect as much as possible (given the limitations related to the use of routinely collected data) contemporary guideline diagnostic criteria (lines 368-370). Temporal changes in both the guideline diagnostic criteria used by clinicians and the degree of diagnostic certainty are relevant biases for longitudinal EHR-based studies to consider and the Discussion section has been expanded accordingly (lines 442-445). The classification term ‘stringent’, used in measuring the specificity of the definition used by studies, has also been amended to ‘specific’ to improve clarity (lines 123 onwards). Comment 2: “Paper is missing focus of diagnostic or therapeutic issues in world literature on gout, as both are a challenge” The objective of the manuscript was to examine the variation in methods, results, reporting and risk of bias in EHR-based studies evaluating pharmacological management of gout. Other specific therapeutic and diagnostic issues in the wider gout-based literature were therefore not examined. None of the EHR-based studies in the review performed adjacent diagnostic assessment and so we were not able to extract information pertaining to issues in diagnosis. The review does however highlight in the Discussion section the problem of suboptimal gout medication management that is recognised globally and is also supported by EHR-based studies [e.g. 1, 2] (amendments made to lines 382-389 to reflect this). A related point is that the diagnostic process used in clinical practice has evolved over time; a recommendation to consider this has been added to the Discussion section (lines 442-445). Reviewer 2 Comment 1 “A very clear and sound study, addressing the variation in methods, results, reporting and bias risks in EHR-based gout studies. Recommendations to improve studies using EHR-systems are described. Therefore the study answers the study questions. I have no additional remarks.” Thank you for the positive review. References 1 Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Annals of the rheumatic diseases. 2014 Apr;74(4):661-7. 2 Singh JA, Hodges JS, Toscano JP, Asch SM. Quality of care for gout in the US needs improvement. Arthritis and rheumatism. 2007 Jun 15;57(5):822-9. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0224272.r002
10 Oct 2019 Decision Letter - Michael Nurmohamed, Editor Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review PONE-D-19-22874R1 Dear Dr. Crossfield, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. 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With kind regards, Michael Nurmohamed, MD, PhD 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 Reviewer #2: 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 Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: (No Response) ****** 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 Reviewer #2: 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 Reviewer #2: 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: Thanks for the nice evaluative analytical study in order to improve gout care Paper is ready for publication Reviewer #2: The manuscript technically sound, and do the data support the conclusions. I have no further questions ****** 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: Yes: Tim L Jansen Reviewer #2: No https://doi.org/10.1371/journal.pone.0224272.r003
Formally Accepted
16 Oct 2019 Acceptance Letter - Michael Nurmohamed, Editor PONE-D-19-22874R1 Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review Dear Dr. Crossfield: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Prof.Dr Michael Nurmohamed Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0224272.r004

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