PONE-D-23-08773Identification of People with Rare Diseases in Administrative Healthcare Records:

A Case Study of HIV in British Columbia, CanadaPLOS ONE

Dear Dr. Emerson,

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.

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Edward Nicol, PhD

Academic Editor

PLOS ONE

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“I have read the journal's policy and the authors of this manuscript have the following competing interests: JSGM is the Executive Director and Physician-in-Chief of the BC Centre for Excellence in HIV/AIDS, a provincial program serving all BC health authorities, and based at St. Paul’s Hospital-Providence Health Care. JM’s Treatment as Prevention® (TasP®) research, paid to his institution, has received support from the BC Ministry of Health, Health Canada, Public Health Agency of Canada, Genome BC, Vancouver Coastal Health and VGH Foundation. Institutional grants have been provided by Gilead, Merck and ViiV Healthcare. JSGM received no specific funding for this work and has no competing interests. VDL is funded by a grant from the Canadian Institutes of Health Research, the Canadian Foundation for AIDS Research (CANFAR Innovation Grant – 30-101), and has received honoraria for the CROI Ambassador Program from ViiV Healthcare. KK is funded by a Michael Smith Health Research BC Research Trainee Fellowship (grant number: #RT-2022-2559), a CTN Postdoctoral Fellowship (no grant number), and a Canadian Institutes of Health Research Postdoctoral Fellowship (grant number: HIV 181935)”

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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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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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: No

Reviewer #2: Yes

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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

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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: This is a well-written manuscript describing the sensitivity and specificity of various algorithms to identify people with HIV as an adjunct to a curated database of people with HIV in British Columbia. I have several suggestions/comments and points of clarification.

1. Introduction - overall the introduction is very long and could be shortened. In particular, most readers will be aware of the tradeoffs between sensitivity and specificity, and the lengthy explanation of these terms could be abbreviated.

2. The authors describe HIV as a "rare" disease in British Columbia. More details about the HIV rates and demographics of people with HIV in Canada would be helpful.

3. The algorithms evaluated only included HIV encounters and hospitalizations, and did not take into account laboratory test results (e.g., viral load frequency) or ART prescriptions, although presumably these data were available. Please explain why these were not utilized in the algorithms investigated, and/or include additional algorithms that include these factors (e.g., see Ridgway et al. Comparison of algorithms for identifying people with HIV from electronic medical records in a large, multi-site database, JAMIA Open, Volume 5, Issue 2, July 2022).

4. The authors evaluated sensitivity and specificity of the chosen algorithms by certain demographic features (e.g., sex) but not by race. I would suggest examining the performance characteristics of the algorithms broken down by race as well, given that Black individuals are disproportionately impacted by HIV and it would be imperative to ensure that algorithms perform equally well for all racial groups.

5. The algorithms selected by the authors include the requirement for 5 HIV encounters within 12 months. This is very frequent. While PWH may have had more frequent encounters with HIV providers earlier in the study period, more recently it is not uncommon for PWH with well-controlled HIV to only see providers once or twice a year. Are the algorithms more accurate earlier in the study period? Please comment on how changes in HIV care/practice over time may impact the performance characteristics of the algorithms over time.

Reviewer #2: It is a very well written article.

The introduction is very comprehensive (on the long side); it is a very complete review of the topic of using administrative health records for building databases of specific diseases and which the criteria should be fulfilled in the design of algorithms for purposes of building the database and for the validation. This article also reviews basic concepts (In the main article and the supplement) that are relevant (I.s.: sensitivity/specificity, etc.) for the reader to understand the process.

The methodology is clearly delineated and very detailed.

The algorithms studied would be very specific for one disease process (HIV) and one geographic area (British Columbia), and as such would not be generalizable to other rare diseases or systems. However, the rigorous methodology that was employed would be a map or guide for others to follow.

Specific concerns: The sample that was used for validation of the population without the disease process (without HIV), is derived from the population that has the disease process at a later date. Although the authors make reference to this weakness in their discussion, it should be further emphasized that the sample without HIV may not be representative of that population in the general population, and hence the performance of the algorithm may vary from what the authors present (even in that specific setting).

Another concern is that this sample seems to be a high utilizer of health care (mean 9 visits), which may not be representative of other areas and may alter in important ways the performance of the algorithm.

With all the caveats, as said before, this manuscript would be a very useful resource and tool for others that would like to design administrative health records based algorithms for research or other purposes.

Minor issues:

Typos: Page 10, line 226; page 13, line 287. The first row for 12 months does not align for the 24 and 36 months. Although it is clear why and this is explained in the Tables in the appendix, it is not explained here and it can make the reader not realize it and interpret the data in a wrong way.

Figure 3 and others: The first row for 12 months(P1H1) does not align with the first row for the 24 and 36 months (P1H2). Although it is clear why and this is explained in the Tables in the appendix, it is not explained here and it can make the reader not realize it and interpret the data in a wrong way (not everyone reviews the appendix information).

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-08773R1Identification of people with rare diseases in administrative healthcare records: a case study of HIV in British Columbia, CanadaPLOS ONE

Dear Dr. Emerson,

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. Kindly respond to Reviewer #2's comment. Please submit your revised manuscript by Sep 29 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Edward Nicol, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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

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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: (No Response)

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: (No Response)

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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: (No Response)

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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: (No Response)

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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: (No Response)

Reviewer #2: I have a minor comment, in reference to one made by the other reviewer. I consider HIV to be a low prevalence disease (in the 0.2% rate in BC), but not a rare disease (by FDA definition, for the USA, a disease present in less than 200,000 individuals in the USA (about 0.05% of the current population). Somewhere in the text, the authors may want to comment in the Canadian definition of rare disease.

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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

Reviewer #2: No

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[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.

Identification of people with low prevalence diseases in administrative healthcare records: a case study of HIV in British Columbia, Canada

PONE-D-23-08773R2

Dear Dr. Emerson,

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.

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Kind regards,

Edward Nicol, PhD

Academic Editor

PLOS ONE

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