PONE-D-22-18687PREventing Mild Idiopathic SCOliosis PROgression (PREMISCOPRO): a protocol for a Randomized Controlled Trial Comparing Scoliosis-specific Exercises with Observation in Mild Idiopathic ScoliosisPLOS ONE

Dear Dr. Diarbakerli,

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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ACADEMIC EDITOR:Criteria for included age, 10 years and 14 years to be revisited.Consider the measurement error of 5 degree while using Cobb's angle.Is sample size based on stratificationadherence measured and compliance, not to be confused. To be made clear Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact. For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. 

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Please submit your revised manuscript by Oct 21 2022 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,

Asir John Samuel, Ph.D.

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 

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https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. 

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

3. Please ensure that you refer to Figures 1 and 2 in your text as, if accepted, production will need this reference to link the reader to the figure.

4. We note that the original protocol that you have uploaded as a Supporting Information file contains an institutional logo. As this logo is likely copyrighted, we ask that you please remove it from this file and upload an updated version upon resubmission.

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 

Additional Editor Comments:

Congratulate for your wonderful work. However, modifications as suggested by the reviewers to be incorporated.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: 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

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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Congratulations to the author/s for planning the research in a very important area. The protocol is well written and has followed the randomized controlled trial protocol guidelines appropriately. However, few minor revisions should be done before considering for acceptance as mentioned below:

1) Intervention image with proper labelling can be added for more clearance about the technique.

2) Reference manager should be followed for a citation and few of the references in the list are incomplete.

Reviewer #2: This protocol address a very relevant question about the role of exercises in preventing scoliosi progression. This is a crucial point in current knowledge about scoliosis treatment.

I have some suggestions about the inclusion criteria.

I would exclude patients below 10 years, so to include patients in a higher risk phase and only AIS. I would exclude also patients older than 14, since we can expect growth to be very close to the end. I understand that using the Sanders and Risser scores would help about this, but I would be more selective.

Since curves up to 24° will be included, and the measurement error of Cobb is 5°, I would wait 30° to brace patients. Otherwise there is the theoretical risk to brace a patient that changes from 24 to 25 or 26 which is not actually a changed and showing and acceptable condition.

I would also add other secondary outcomes: the number of improved patients (6° or more), the number of patients who completed growth below 30°, which is a main goal according to SOSORT guidelines. I think that reducing the progression rate even without totally stop it would be successful for the patients in case the threshold of 30° is not reached.

Please describe the protocol of exercises applied. Will it be SEAS, Schroth or other?

Blinding: I suggest to have a blind evaluation by an expert of the radiographies to doublecheck the treating physician's evaluation. This would make the paper much stronger.

Reviewer #3: This is an interesting study looking at Scoliosis specific exercises to reduce the number of adolescents with scoliosis progression of more than 6 degrees.

Some minor comments worth addressing.

1. Although the sample size is based on 90 people, did the authors consider stratification of perhaps for primary curve and age, as these were adjusted for in the models?

2. In the data analysis section, can the authors include that results will be present according to CONSORT.

3. A CACE analysis will be used, can the authors define compliance here.

4. In the data analysis, it would help readability to split primary and secondary outcome analysis. Also some outcomes are collected at repeated time points, does the analysis take this into account?

5. Can the authors also state the results will be presented as treatment effect, confidence interval together with associated p-values.

6. How is treatment adherence measured, not to be confused with compliance, or can the authors really clarify this.

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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 #2: 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.

PONE-D-22-18687R1PREventing Mild Idiopathic SCOliosis PROgression (PREMISCOPRO): a protocol for a Randomized Controlled Trial Comparing Scoliosis-specific Exercises with Observation in Mild Idiopathic ScoliosisPLOS ONE

Dear Dr. Diarbakerli,

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.

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

ACADEMIC EDITOR: Please insert comments here and delete this placeholder text when finished. Be sure to:

The issues I raised previously appear to have been addressed. However, minor revision need to be made as suggested by one of the reviewer. 

For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. 

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

Please submit your revised manuscript by Jan 22 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,

Asir John Samuel, Ph.D.

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:

The issues raised previously appear to have been addressed.

However, minor revision need to be made as suggested by one of the reviewer.

The comments are as follows,

Again, I think this is an overall fundamental and well designed study. Nevertheless, there are some points that are questionable since are not consistent with current literature.

Including patients younger than 10 means mixing JIS and AIS, makes results more confuse will take longer to reach the final outcomes increasing costs. Stating that this consistent with your previous publications is weak, since the rest of the world differs from this.

There are 2 protocols with somehow solid data showing positive results in the field: Schroth and SEAS. To perform one of them the PTs need a specific certification. The authors state they will do something different coming from the literature and taking ideas from different approaches. What is the experience of the PTs administrating this treatment to patients? Do they have any certification (Schroth, SEAS or other)? How can readers know about the quality of the treatment? Please give more details.

Also, the protocol is not clear about how many training sessions will be administered after the initial phase. Again, Schroth and SEAS have a quite clear protocol to ensure quality and a continuous contact with the therapist, since if patients work too much by themselves the precision in the Active self correction tend to be less precise, and this can affect the final results.

I appreciate the fact that radiographs will be assessed in blind. I would add a sentence about this also in the pragraph "blinding".

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

**********

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 #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All the queries raised are answered successfully by the authors. However, in the future studies more meticulously the limitations of the study should be addressed

Reviewer #2: Again, I think this is an overall fundamental and well designed study. Nevertheless, there are some points that are questionable since are not consistent with current literature.

Including patients younger than 10 means mixing JIS and AIS, makes results more confuse will take longer to reach the final outcomes increasing costs. Stating that this consistent with your previous publications is weak, since the rest of the world differs from this.

There are 2 protocols with somehow solid data showing positive results in the field: Schroth and SEAS. To perform one of them the PTs need a specific certification. The authors state they will do something different coming from the literature and taking ideas from different approaches. What is the experience of the PTs administrating this treatment to patients? Do they have any certification (Schroth, SEAS or other)? How can readers know about the quality of the treatment? Please give more details.

Also, the protocol is not clear about how many training sessions will be administered after the initial phase. Again, Schroth and SEAS have a quite clear protocol to ensure quality and a continuous contact with the therapist, since if patients work too much by themselves the precision in the Active self correction tend to be less precise, and this can affect the final results.

I appreciate the fact that radiographs will be assessed in blind. I would add a sentence about this also in the pragraph "blinding".

Reviewer #3: All previous comments have been checked and the authors have addressed all comments. I have no further comments.

**********

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 #2: No

Reviewer #3: 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.

PREventing Mild Idiopathic SCOliosis PROgression (PREMISCOPRO): a protocol for a Randomized Controlled Trial Comparing Scoliosis-specific Exercises with Observation in Mild Idiopathic Scoliosis

PONE-D-22-18687R2

Dear Dr. Diarbakerli,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Felicity Hey

Staff

PLOS ONE

On behalf of 

Dr. Asir John Samuel

Academic Editor