PONE-D-24-26791Efficacy and cost-effectiveness of Chuna manual therapy for temporomandibular disorder: A randomized clinical trialPLOS ONE

Dear Dr. Lee,

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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We look forward to receiving your revised manuscript.

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Essam Al-Moraissi

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: 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 article presents detailed data and analysis on the efficacy and cost-effectiveness of CMT for TMD. However, compared to the extensive outcome data, there needs to be more sufficient explanation and discussion. Unnecessary data should be excluded, or an explanation and discussion should be added to help the reader understand.

Additionally, I would like to suggest the following comments:

1. The abstract needs to include more information about the trial settings. For example, a sentence like “They underwent eight sessions of CMT and usual care for four weeks” without mentioning the group assignment confuses how the interventions and control were designed. We recommend adding information about the methods to the abstract and describing only the key points in the results section.

2. In the introduction, it is not appropriate to express the content of reference number 5 as “conservative treatments,” and the intervention applied in that study should be specifically expressed. In addition, the evidence for other treatments should not be determined based on only a few research results; more comprehensive evidence should be presented.

3. The method of CMT and physical therapy is not specifically presented. There should be a specific description that allows the reader to reproduce the procedure. In addition, since the treatment applied to each patient is different, a specific explanation of the criteria for why the treatment is applied differently to each patient is necessary.

4. The evidence for expressing the physical therapy in the control group as “commonly used methods” should also be described.

5. The trial timeline needs to be clearly recognized. Please present the timeline in a figure or table and unify the expression of each time point in the manuscript.

6. The manuscript's structure does not comply with CONSORT. Please appropriately reorganize the contents of 'Methods' and 'Results' using the headings and subheadings. In particular, please clearly distinguish between the contents on efficacy and cost-effectiveness.

7. Moving the baseline demographics in Table S2 into the main text seems appropriate.

8. To increase visibility, I suggest organizing the results in Table 1 into separate tables by outcome measures.

9. The primary outcome measure for the research hypothesis and the other secondary outcome measures are not distinguished throughout the study. The results section should be described in separate paragraphs by outcome measures. In addition, in terms of conclusion, the results of the primary outcome measure should be presented first.

Reviewer #2: The authors demonstrated the efficacy and cost-effectiveness of Chuna manual therapy compared to usual therapy in patients with temporomandibular disorder. This study has provided strengthened evidence for the clinical effectiveness and cost-effectiveness of Chuna manual therapy for these patients through randomized controlled trials, which have had limited evidence so far. However, some clarifications are needed to ensure the robustness of this evidence.

Major comments

First, there is a lack of explanation on how various pieces of information, such as clinical outcomes, utilities, and costs, are connected to the conclusions. For example, in this study, there was no significant difference in pain outcomes between Chuna manual therapy and usual care, yet the discussion highlights the reduction of pain as a strength of this study. A more logical explanation of this aspect should be provided. Additionally, the conclusion in the abstract states that Chuna manual therapy is a safer option compared to usual care, but it does not mention whether there is any statistical significance between the two groups.

Secondly, while the paper includes a lot of information on clinical outcomes, utilities, and costs, it lacks detailed explanations for each piece of information, making it difficult to obtain sufficient and specific details. For example, it is unclear what treatments are included in Chuna manual therapy or usual care, and whether patients received more than one treatment. Although this can be found in the supplemental table, it is crucial for understanding the intervention and should be mentioned in the methods section. Additionally, while the QOL outcomes are presented, it is necessary to explain the score ranges of each tool and whether a higher score indicates a higher or lower QOL to properly understand the results.

Thirdly, it is recommended to reorganize the sequence of the paper’s flow. The main points that the reader needs to know should be presented first, followed by the supporting evidence, to help the reader better understand the content.

Specific comments for each section

Abstract

1) Lines 35-36: Recommend including the WTP value.

Introduction

1) Lines 58-61: This part should be included in the methods section to explain the unit costs of CMT. Additionally, it is necessary to provide more details on why a cost-effectiveness study is needed (e.g., for reimbursement from NHI).

Methods

1) Lines 90-91: Which outcome was the assessor not involved in? Please clarify this. Additionally, since most QOL tools are measured by self-reported questionnaires, how is assessor blinding meaningful in this context?

2) Lines 94-96: What techniques of CMT were included in this RCT? Please provide a potential list of CMT techniques here, or the exact list if it has already been selected.

3) Lines 97-99: Please clarify whether a patient can receive only one treatment from the usual care list or more than one treatment from the list.

4) Line 101: Please mention the medications that were possibly administered to both groups.

5) Line 103: Provide the rationale for why the primary outcome was assessed at 5 weeks rather than at a longer follow-up.

6) Lines 103-108: Provide detailed information about the outcome measures (e.g., range of scores, questionnaire composition, what higher scores mean) to understand the meaning of the scores.

7) Lines 119-124: Which items were included in the costs (e.g., doctor’s visits)? Please add the list of items that were included in the cost estimate.

8) Lines 132-136: Recommend moving this section before the 'Unit Cost' section so that readers can understand the perspectives first and then learn how to calculate costs according to the two perspectives.

9) Lines 142-145: Please revise the sentence to correct the grammar. Also, clarify which covariates were added and the meaning of significance (e.g., significance level of 0.05 based on the p-value).

10) Lines 157-158: The results of the WTP were estimated from a publication in 2012, which was 12 years ago. Are they still applicable in 2024?

Results

1) Lines 174-175: What do the scores of CMT 7.0 and usual care 6.5 refer to? Present the p-value indicating that there is no significant difference between the two groups.

2) Lines 183-187: The method does not mention that medication can be used for both the intervention and comparator. Please add this information.

3) Lines 190-197: Since the method does not explain the scores for each outcome measure, it is difficult to understand the meaning of the direction and magnitude of each score. I recommend adding this information to both the methods section and the footnote of the table. Additionally, it is necessary to provide more explanation in the discussion to derive conclusions about the implications of the scores for various clinical outcomes.

4) Lines 216-219: Please add the meaning of 'faster recovery' and specify what the survival analysis pertains to.

5) Lines 248-251: Please use the correct unit for ICER ($/QALY) throughout the manuscript.

Discussion

1) Lines 307-309: Same comments as in Methods 1). The outcome measures include self-reported questionnaires. In this case, can we say that assessor-blinding is useful?

2) Lines 275-280: Pain showed non-significant results, but function improved, and it is understood that the quality of life (QOL) improved as a result. Please provide a more detailed explanation of this by discussing the meaning of the QOL measures for each dimension.

3) Lines 291-292: In the results of this study, significant results for pain were not observed, yet there is a discrepancy with the reported pain improvement in the discussion. To maintain consistency between the study results and the discussion, it is necessary to thoroughly address this discrepancy.

4) Lines 300-302: Similar to the previous question, please explain the discrepancies regarding reducing pain in relation to the results of this study.

5) Lines 314-315: What is the meaning of a conservative treatment option? Also, Draw meaningful conclusions based on all the outcomes included in the results.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-24-26791R1Efficacy and cost-effectiveness of Chuna manual therapy for temporomandibular disorder: A randomized clinical trialPLOS ONE

Dear Dr. Lee,

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.

==============================

 both Reviewers have been recommended  further minor revisions. Kindly address these minor revision before final consideration for your paper

==============================

Please submit your revised manuscript by Mar 08 2025 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,

Essam Al-Moraissi

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 #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 #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

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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 #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 appropriately revised overall, but some parts require supplementation. Here are some suggestions:

1. Revise the “Study timetable” table that appears twice.

2. Please indicate the exact book “textbook of Chuna Manual Medicine” as a reference.

3. “Efficacy” and “effectiveness” are used interchangeably throughout the manuscript. Considering the pragmatic study design, please consider whether it would be more appropriate to use “effectiveness” rather than “Efficacy.”

4. The criteria for treatment selection still need to be clarified. Six CMT techniques are presented, but the symptoms or criteria for each technique applied should be described in the methods or discussion part. The same explanation is required for physical therapy in the control group, and in particular, TENS and ICT were applied to different patients, so criteria for distinguishing them should be provided.

5. Please indicate the statistically significant results in Table 3.

6. There was a significant improvement in some of the functional indices (JFLS, ROM) and quality of life indices (EQ-5D-5L, EQ-VAS, SF-12). However, expressing that the overall function and quality of life improved is not appropriate. It is necessary to describe exactly which functions and quality of life improved in a limited way.

7. The “7.3±0” value in the S2 Table seems to be an error.

Reviewer #3: This review concentrates primarily on the statistical analysis. In general, the analysis seems sound. However, the statistical methods section should be rewritten slightly to clarify the various components of the statistical analysis.

Was the AUC used as a way of time-averaging the endpoint(s)? Please motivate the use of the AUC in this setting.

More generally, note that each study assessment gives rise to one or more endpoints, which are used to assess the hypotheses of the study. With this in mind, please indicate the statistical methods section which endpoints are assessed via which statistical methods, as well as any transformations that are applied before statistical analysis (e.g., the AUC). This should help clarify the flow from data to results to conclusions.

To further elaborate, generally, the structure should be rather parallel, with:

Hypotheses -> Assessments -> Endpoints -> Statistical methods -> Results -> Conclusions

It would be useful to have figures that display longitudinal data --- these could be included just as supplementary figures.

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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 #3: 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.

Effectiveness and cost-effectiveness of Chuna manual therapy for temporomandibular disorder: A randomized clinical trial

PONE-D-24-26791R2

Dear Dr. Lee,

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,

Essam Al-Moraissi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: 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 #3: (No Response)

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

Reviewer #1: Yes

Reviewer #3: (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 #3: (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 #3: (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: Previously presented comments have been adequately modified.

The methods, results, and discussions described in this article are suitable for publication in this journal.

Reviewer #3: (No Response)

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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 #3: No

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