PONE-D-24-13515Cross-Sectional Analysis of National Testosterone Prescribing through Prescription Drug Monitoring Programs, 2018-2022PLOS ONE

Dear Dr. Selinger,

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 pay particular attention to following areas. 

1. It is essential to clarify whether incidence or prevalence was calculated. 2. The conclusion should be limited to what can be arrived from the available results. 3. I would recommend improving the discussion with special emphasis on comparison with global trends during the studied period and trends in the region before the period covered by this study. 

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Appuwawadu Mestri Nipun Lakshitha de Silva, MBBS, MD

Academic Editor

PLOS ONE

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Partly

Reviewer #2: Partly

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

Reviewer #1: N/A

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: No

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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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: In my opinion, the rationale of this kind of analysis is not very clear. The increase of testosterone use can be concerning and may deserve to be monitored, but the overall prevalence is quite low (also in 2022), with the exception of subjects >=45 years old.

Some comments and suggestions:

1. The study is mainly descriptive. In my opinion, a few statistical analyses (e.g. chi-square for trend; chi square test to compare prevalence by gender) may be helpful.

2. In the methods section you stated that incident rates were calculated, and data were reported in Table 1 and figure 4. This means that it was possible to estimate the number of new TT users? It seems likely to me that subjects reported in table 1 are prevalent, and not incident, cases.

3. I would like to suggest to better clarify how the expected incidence (prevalence?) in 2021-2022 was estimated, and what the values reported in figure 3 represents (what does 1.8% stand for?).

4. It is not very clear to me what is your hypothesis for the increease in TT users during the pandemic period. A mis-diagnosis of hyopogonadism, due to an increase in symptoms associated to a decrease in mental well-being?

5. Geographical differences in the prevalence of TT prescription were observed, but not discussed.

Moreover, it seems to me that the greater than expected rise in users in the 2021-2022 period was limited to very few states (mainly Texas and Arkansas).

Have you any hypothesis about the reasons of these differences?

6. Abstract - results section: The sentence "The number of people treated annually with TT increased 439,659, a 27% rise with 80% of this increase during..." is not very clear. Maybe it could be changed in "In 2022 there was a 27% relative increase of subjects treated with TT (+439,659 cases compared with 2018). The increase was more evident in the pandemic period, with a rise in the prevalence from ... to ..."

Reviewer #2: The authors present a evaluation on the trends in testosterone prescription use in the US. As previously seen, the overall trend is upward with more prescriptions being written/filled. The underlying reasons for this are not investigated by the methodology. I therefore caution the authors on the conclusions presented in the abstract and discussion that any specific link to COVID-19, mental health, or marketing practices. The link to the pandemic should be presented less strongly as the number of confounders is unknown and the methodology do not address or assess this link. For example the trend is going upward throughout the study period and the last two years happen to be during the pandemic.

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Reviewer #2: No

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PONE-D-24-13515R1Cross-Sectional Analysis of National Testosterone Prescribing through Prescription Drug Monitoring Programs, 2018-2022PLOS ONE

Dear Dr. Selinger,

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 clarify whether Figure 4 reports incidence rather than prevalence and report the how the incidence was reported in the methods section. 

Please submit your revised manuscript by Sep 13 2024 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,

Appuwawadu Mestri Nipun Lakshitha de Silva, MBBS, MD

Academic Editor

PLOS ONE

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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: (No Response)

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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

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

Reviewer #1: N/A

**********

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: No

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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

**********

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: It seems to me that most of the reviewers' comments and suggestions have been addressed in a satisfactory manner. I still have a revision to suggest:

I'm still not very convinced that in Figure 4 it is reported incidence. The values seems very similar to that reported in table 3 (total column). This means that almost all TT users were "new users"? In any case, I would like to suggest to better explain in the methods section (line 87, page 11) how incident users were defined (subjects with a TT claim in a year and with no TT claims in the previous one?)

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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

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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.

Cross-Sectional Analysis of National Testosterone Prescribing through Prescription Drug Monitoring Programs, 2018-2022

PONE-D-24-13515R2

Dear Dr. Selinger,

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,

Appuwawadu Mestri Nipun Lakshitha de Silva, MBBS, MD

Academic Editor

PLOS ONE

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