PONE-D-23-01919Internet search analysis on the treatment of rheumatoid arthritis: What do people ask and read online?PLOS ONE

Dear Dr. Yamaguchi,

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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The paper was well written following a standard format. Please address the concerns raised by reviewers prior to the final decision.

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Please submit your revised manuscript by Apr 16 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.

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We look forward to receiving your revised manuscript.

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Yoshito Nishimura, MD, PhD, MPH

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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Thank you for your submission. Please revise the manuscript per reviewers' comments.

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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: Yes

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 an interesting study summarizing the reliability of information on the Internet regarding the treatment of rheumatoid arthritis. Since the Japanese language is used in Japan, there are relatively fewer sources of information than in other languages, and patients with limited media literacy often believe incorrect information. The data can objectively demonstrate this situation, however, I suggest some revisions for publication.

As the authors point out, the fact that only Japanese is used is a limitation, but on the other hand, Japanese is a unique language in the world, used almost exclusively in Japan and as a native language by most Japanese people, thus the results of this study may represent a one-to-one correspondence with domestic trends in Japan. From this point of view, it would be possible to discuss the differences between the results in Japan and other countries.

The study was conducted in the midst of COVID-19 pandemic. It is reported that it was difficult to receive out-patient treatment for chronic diseases during COVID pandemic, and it is possible that patients sought information sources on the Internet. This point should be discussed.

As for the searching term, it would be appropriate to indicate the words actually inputted in kanji characters instead of romaji.

Figure Legend should be added as it seems to be missing.

Please state the official name of the IRB which not requiring ethics review.

Please tell us the version of Google Chrome you used.

Google may change the search results depending on where you accessed the Internet, so please share information such as place names and IP addresses rather than simply stating "Japan" if possible

Reviewer #2: I was glad to review this article which was really interesting.

I suggested a few point to revise as below.

Regarding the terms such as ''Single surgeon personal'', ''Websites maintained by individual surgeons without an institutional affiliation'' especially in Table 3, I know some area orthopedic surgeon is treating rheumatoid arthritis. However, those patients are usually treated by rheumatologist(or physician) in general all over the world. Therefore, this term may need to be changed to other phrase. For instance, single physician or surgeon personal or single medical doctor, which include physicians and surgeon.

Regarding in Table 2, there was a word ''Humira''. It should be changed to generic name, Adalimumab''.

Lastly, for all the tables, probably it can be sorted clearly so subscribers understand better.

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Reviewer #1: Yes: Yuki Otsuka

Reviewer #2: No

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PONE-D-23-01919R1Internet search analysis on the treatment of rheumatoid arthritis: What do people ask and read online?PLOS ONE

Dear Dr. Yamaguchi,

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 submit your revised manuscript by May 20 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,

Yoshito Nishimura, MD, PhD, MPH

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.

Additional Editor Comments:

Dear Authors, thank you for submitting your revision. While the manuscript has been improved according to the comments from 2 reviewers, additional comments were brought up to further secure the quality of the manuscript. Please refer to the comments by reviewer 3. I look forward to your revision.

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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

Reviewer #3: (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

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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 #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: Yes

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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: The manuscript is well addressed, however, the manuscript should be proofread by a native English speaker.

Reviewer #2: I was my pleasure to review this article. All minor reviews were appropriately addressed. I agree with publishing this.

Reviewer #3: I enjoyed reading your article. The following are my comments after reviewing it.

- This PAA system reflects the tendency of questions of what time period? Today? For the last 1 week? For the last one month?

Does it reflect the general tendency of questions correctly or is there a possibility that the results may be affected by one temporary "phase" of search which is affected by a recent popular TV program for example? I think if the data sampling period is too short, there is the risk of misinterpreting a random rise in the search number as a general trend.

- I assume google search system tries to direct viewers to a website that gives quick and easy answer to each question. From that perspective, the websites that were linked to PAA questions do not necessarily have to be detailed, high quality or thorough regarding the general topic such as "treatment in general". You concluded that the quality of websites on RA treatment was insufficient. However, from this study, this big conclusion cannot be obtained because you did not collect the websites that explains "RA treatment in general." You assessed websites that "answered each commonly asked question" and assessed their quality. If you want to argue that "websites on RA treatment has poor quality", you would have to directly go to the websites that pop up with the general search "rheumatoid arthritis/treatment" etc, not the website that were linked with PAA. Once again, the websites that you picked up by PAA are the ones that likely give people "easy answers." for each small question.

- I think there is weakness of this search method. This study is based on the premise that people start searching with specific 6 combinations of terms. However, this is not always true in the real world. For example, if people searched with more specific terms such as "rheumatoid arthritis, biologics", worrying about the high cost of biologics, that tendency would not be reflected on the result of this study. Others may search with "rheumatoid arthritis, side effects" or "rheumatoid arthritis, methotrexate" "rheumatoid arthritis, infectious risk". Many patients often have specific concerns and they tend to search with more specific terms depending on their concerns.

Therefore, this study dose shed light to one aspect of people's concerns affected by random bias from the search engine but does not reflect the real-life frequency of the general population. Actual interview style studies from a smaller RA cohort would have less bias, reflecting the true tendency of question.

- Are there any websites that were rated as "good" in Japan in general? Even academic websites that were linked failed to meet "good quality" criteria. Can this be a problem of the outcome measures that were used? Or can this be a misguidance by google to a low quality website? Or does this reflect poor quality of Japanese online resources in general?

If you think there might be a problem with the quality measures, I would want to hear more about why and in what way. (More details in the next section.) If you think it could be a google misguidance problem despite the existence of high quality websites in Japan, you might want to mention examples of websites with "good quality" in Japan. If you think this is because of the general paucity of such websites in Japan (although I do not believe this study can directly support this conclusion), you might want to elaborate on that.

- Regarding the validity of the quality measures, it concerns me that social media is rated as the highest quality compared with academic or medical practice websites because it is contraty to my intuition. I would imagine academic entities would provide more accurate, less biased and updated information than social media, which has no guarantee regarding bias or background knowledge of the authors. You did mention other studies using the same quality measures in the discussion. Do you think these measures appropriately evaluated the quality of RA websites? Do you think that academic website has information with lower quality than social media? If you think there is some problem with these quality measures, you should comment on that in the discussion because I think these questions are crucial to this paper. The reliability of outcome depends on the validity of these quality measures.

Overall, I liked this novel attempt in filling the knowledge gap between patients and physicians. I do think your messages here at least partially hold truth from personal clinical experience. However, I also think a few questions regarding logics and the design that were mentioned above should be addressed.

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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: Yes: Yuki Otsuka

Reviewer #2: No

Reviewer #3: Yes: Shuhei Hattori

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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.

PONE-D-23-01919R2Internet search analysis on the treatment of rheumatoid arthritis: What do people ask and read online?PLOS ONE

Dear Dr. Yamaguchi,

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 submit your revised manuscript by Jun 09 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,

Yoshito Nishimura, MD, PhD, MPH

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.

​

Additional Editor Comments:

Thank you very much for all the time and efforts revising the manuscript. One reviewer pointed out a few issues that needed to be addressed prior to acceptance. Please review the comments and proceed with your edits.

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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 #3: (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: (No Response)

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #3: 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 #1: Yes

Reviewer #3: 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 #3: 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: The manuscript has been fully revised. All of my points have been addressed appropriately and faithfully. I have no additional comments. I believe it is worthy enough to be published.

Reviewer #3: Thank you for revising the manuscript. As I mentioned in the previous comments, overall, I had 2 major questions to be addressed. 1, uncertainty of google search system regarding sampling bias. 2, whether outcome measures for quality assessment of websites were appropriate or not.

You addressed both of these questions better in the discussion of the latest manuscript. Given that you admitted the limitations of the current methods, the conclusion appears less biased.

I have one more request regarding the second conclusion of the study. I would like to hear a little more details regarding the low quality of websites. I would like to see what elements are lacking. You state that websites should have better quality. You must have assessed the websites based on 3 scoring systems and you should know which part websites scored less than ideal. It would be better to show what improvements are to be made than to just say they have low quality.

Other than that, I have no additional comments to make.

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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: Yes: Yuki Otsuka

Reviewer #3: Yes: Shuhei Hattori

**********

[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.

Internet search analysis on the treatment of rheumatoid arthritis: What do people ask and read online?

PONE-D-23-01919R3

Dear Dr. Yamaguchi,

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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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,

Yoshito Nishimura, MD, PhD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for all the hard work to submit your revised manuscript. The quality of manuscript has been substantially improved after the rounds of revision.

Reviewers' comments: