PONE-D-24-07542Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019PLOS ONE

Dear Dr. Kaneda,

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 reviewer feedback is provided below.  Please submit your revised manuscript by Jun 07 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,

Narcyz Ghinea

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

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

2. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and previous work in the [introduction, conclusion, etc.].

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

[If the overlap is with the authors’ own works: Moreover, upon submission, authors must confirm that the manuscript, or any related manuscript, is not currently under consideration or accepted elsewhere. If related work has been submitted to PLOS ONE or elsewhere, authors must include a copy with the submitted article. Reviewers will be asked to comment on the overlap between related submissions (http://journals.plos.org/plosone/s/submission-guidelines#loc-related-manuscripts).]

We will carefully review your manuscript upon resubmission and further consideration of the manuscript is dependent on the text overlap being addressed in full. Please ensure that your revision is thorough as failure to address the concerns to our satisfaction may result in your submission not being considered further.

3. Thank you for stating the following financial disclosure: 

"This study was funded in part by the Medical Governance Research Institute. This non-profit enterprise receives donations from a dispensing pharmacy, namely Ain Pharmacies, Inc.; other organizations; and private individuals. This study also received support from Tansa (formerly known as the Waseda Chronicle), an independent nonprofit news organization dedicated to investigative journalism. There was no grant number for the donation to the Medical Governance Research Institute."

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." 

If this statement is not correct you must amend it as needed. 

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

4. Thank you for stating the following in the Competing Interests section: 

"Dr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose. 

Regarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries."

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. 

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

5. We note that your Data Availability Statement is currently as follows: [All relevant data are within the manuscript and its Supporting Information files.]

Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).

For example, authors should submit the following data:

- The values behind the means, standard deviations and other measures reported;

- The values used to build graphs;

- The points extracted from images for analysis.

Authors do not need to submit their entire data set if only a portion of the data was used in the reported study.

If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories.

If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) 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. If data are owned by a third party, please indicate how others may request data access.

6. 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. 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: 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: This manuscript looks at trends in the amount of payments to breast cancer specialists by pharmaceutical companies. It is an addition to the growing literature documenting payments from pharmaceutical companies to physicians working in a variety of specialties. Studies mainly, but not exclusively, out of the United States also show an association between the receipt of payments and prescribing behaviour. But transparency has not led to any substantial changes in the behaviour of either pharmaceutical companies or physicians. Therefore, while transparency is necessary it is not sufficient to deal with the negative effects of industry payments. In this light, it is necessary for the authors to propose policy measures to deal with the effects of the payments rather than just call for more transparency.

Line 99: In line with the comment above, the authors need to cite evidence that promoting transparency in isolation from other measures will achieve the desired outcome.

Line 104: In the US the disclosures have to name the product associated with the payments. Is that the case in Japan?

Lines 118-119: The authors need to cite literature showing that the recent introduction of medicines has resulted in a clinically meaningful increase in the length of survival and/or a clinically meaningful increase in the quality of life.

Line 152: How many people gathered the data. If it was more than one was it done independently and how were discrepancies resolved? If it was a single person how were errors avoided/detected?

Line 175: What statistical program, and its version number, was used?

Line 272: Neither reference 41 nor 42 discusses concrete evidence that newer CDK4/6 inhibitors offer clinically meaningful increases in overall survival time or quality of life.

Lines 293-294: Who financed the 2022 guidelines and how many of the people on the committee had COI with one or more makers of drugs used in the treatment of breast cancer?

Lines 310-320: Direct or indirect gender discrimination should not be tolerated, but the authors frame their argument around the assumption that attending post-clinical evening lectures sponsored by pharmaceutical companies will improve clinical care whereas the content of these talks is often biased in favour of the products made by the company sponsoring the talk.

Reviewer #2: 

Introduction:

- The author should have included a discussion about the potential conflict of interest that may arise from the relationship between the industry and oncologists, and how this can impact patient care. There is a substantial amount of literature on this topic. I understand the authors want to examine the trend of pharma payment, however, I am sure there already a relationship between Japanese breast oncologists and pharmaceutical companies hence mentioning how this can be detrimental to patient care in case not well controlled is important

- It would have been beneficial to note that these payments or conflicts of interest (COI) could potentially influence the prescribing of breast cancer medications with minimal or negligible efficacy. An example of this is Bevacizumab, which was subsequently withdrawn. Additionally, there is available data on this topic.

Results:

- Authors should consistently use commas after numbers in the thousands.

Discussion:

- The impact of the relationship between the industry and oncologists on patient care is not mentioned in the discussion.

- It could also improve the paper by mentioning the importance of transparency of pharma payments.

-The payment of >100,000 even though a small percentange needs to highlighted. There is a paper by Wright et al, JOP

**********

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: Joel Lexchin

Reviewer #2: No

**********

[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.

Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019

PONE-D-24-07542R1

Dear Dr. Kaneda,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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,

Narcyz Ghinea

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I am happy that the authors have adequately addressed the reviewers' feedback.

Reviewers' comments: