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PONE-D-23-01039Prevalence and Appropriateness of In-Person versus Not-In-Person Ambulatory Antibiotic Prescribing in An Integrated Academic Health System: A Cohort StudyPLOS ONE

Dear Dr. Linder,

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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Juan F. Orueta, MD, PhD

Academic Editor

PLOS ONE

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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: No

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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: Thank you for the chance to review this manuscript, which examines antibiotics prescribed in outpatient settings in an integrated health delivery system in the US, detailing those prescribed with in-person visits versus outside of in-person visit. They found that 19% of antibiotics were prescribed outside of in-person visits (primarily telephone visits). Compared to antibiotics prescribed with an in-person visit, those prescribed outside of an in-person visit were more likely to be chronic or to lack an associated diagnosis. Specific comments are below:

Major:

- I appreciate that diagnoses within a set period were extended across time and visits (all encounter diagnoses on the day of diagnosis by any provider and diagnoses by same provider across next 21 days being examined for possible antibiotic appropriate diagnoses). In contrast, it appears that categorization of visit type (in-person vs non-in-person) was more rigid. For example, if a pharmacy called to clarify a prescription on the day of or day after an in-person visit prompting a telephone encounter with a new prescription, was this classified as a telephone encounter or associated with the preceding in-person encounter? Were these counted as two separate antibiotic prescriptions in two different settings, or only ultimately counted as a telephone encounter (with the prior in-person prescription perhaps cancelled in the EHR?)? Sensitivity analysis around these assumptions seem important to understand out-of-visit prescribing.

- It seems important to re-emphasize that during the study period “at least one diagnosis was required for an in-person encounter, but not for a telephone or patient portal encounter.” Thus I would hesitate to interpret the 42% not-in-person visits without a diagnosis as inappropriate prescribing, but rather inappropriate documentation enabled by different requirements within the EHR for different visit types, leaving the question of appropriateness wide open for these visits, and necessitating further examination in a EHR where/when diagnoses are required.

Minor:

- Given the inclusion of chronic antibiotic use as a category of interest, unclear why antibiotics for urinary tract infection prophylaxis were specifically excluded.

- Would emphasize in methods and discussion/limitation that the specific antibiotic could be inappropriate for the specific diagnosis and yet still classified as “appropriate” in this schema.

- Are dental prescriptions included in these data? Given the focus on global ambulatory prescribing, would be worth noting whether this setting is included or not.

Thank you again for the opportunity to review.

Reviewer #2: This is a very interesting topic, although clearly the world has changed since the study's end. Overall, I had only one major issue.

The introduction is well reasoned.

Methods:

I would clarify you didn't look at antibiotics only prescribed for prophylaxis such as methenamine; nitrofurantoin and bactrim may be much more commonly used for UTI prophy. Also, dapsone for example?

I would assume that even post-COVID, patient portal encounters and many non-visit phone encounters do not require a billing code

The methods are well-described. However, was there a reason specifically for not doing testing for statistical significance? I understand and appreciate the clinical significance. It just makes it quite difficult to say, "more likely to be..."

The rate of patients receiving antibiotics for chronic conditions seems extremely high. Almost as high, in fact, as the total proportion of antibiotics prescribed outside of clinic visits. Although I'm not sure of research supporting this, it is certainly higher than in many large health systems. It is also odd that the most common chronic diagnoses include chronic sinusitis, COPD, and chronic rhinitis (and not, for example, trimethoprim-sulfamethoxazole for PJP prophylaxis). Chronic sinusitis and chronic rhinitis do not seem like conditions necessitating chronic antibiotics. COPD also seems like a very small minority of patients would require chronic antibiotics, as general use of chronic antibiotics goes against international guidelines in this condition. Should this just be "sometimes" rather than "chronic?" As these categories are mutually exclusive, the chronic condition results are somewhat misleading. The fact that not many of these antibiotics are prescribed over refills also makes me suspect that these antibiotics are not really being prescribed for chronic infections.

Discussion: I would expand on some of these limitations in the discussion as well.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-01039R1Prevalence and Appropriateness of In-Person versus Not-In-Person Ambulatory Antibiotic Prescribing in An Integrated Academic Health System: A Cohort StudyPLOS ONE

Dear Dr. Linder,

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.

The authors have provided adequate responses to the previous comments and sufficiently explained the limitations of the study. However, a minor point observed by the reviewer needs to be clarified.

Please submit your revised manuscript by Aug 06 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,

Juan F. Orueta, MD, PhD

Academic Editor

PLOS ONE

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1. 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.

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 #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 #2: Yes

********** 

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

Reviewer #2: 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 #2: Yes

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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 #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 #2: Thank you for addressing these comments. The article is now clearer. However, I have the most minor of revisions to request. On reviewing again, I am realizing that the distinction between adult vs pediatric patients (and internal medicine vs family medicine vs pediatrics) is unclear. Were pediatric patients included as well as adults?

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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 #2: Yes: Sara C Keller

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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.

Prevalence and Appropriateness of In-Person versus Not-In-Person Ambulatory Antibiotic Prescribing in An Integrated Academic Health System: A Cohort Study

PONE-D-23-01039R2

Dear Dr. Linder,

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.

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Kind regards,

Juan F. Orueta, MD, PhD

Academic Editor

PLOS ONE