Optimized braces for the treatment of adolescent idiopathic scoliosis: A study protocol of a prospective randomised controlled trial

Maxence Coulombe; Aymeric Guy; Soraya Barchi; Hubert Labelle; Carl-Éric Aubin

doi:10.1371/journal.pone.0292069

Peer Review History

Original SubmissionMay 8, 2023
1 Aug 2023 Decision Letter - Filippo Migliorini, Editor PONE-D-23-11353Optimized braces for the treatment of adolescent idiopathic scoliosis: a study protocol of a prospective randomised controlled trialPLOS ONE Dear Dr. Hubert, 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 Sep 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. 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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 stating the following in the Competing Interests section: I have read the journal's policy and the authors of this manuscript have the following competing interests: MC and AG are cofounders and shareholders of Modulate Technologies Inc. HL is a cofounder and shareholder of Spinologics Inc. CEA has a discovery grant from the Natural Sciences and Engineering Research Council of Canada, and a R&D grants from Medtronic paid to the university. SB declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We note that you received funding from a commercial source. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Within this Competing Interests Statement, 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 amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf. 3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. 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 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: please follow the SPIRIT guidelines: re-adapt the whole manuscript, state in a sentence that you follow those guidelines and add its related reference, and add the checklist filled in each part as supplementary material. Thank you. Regards, Filippo Migliorini [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: Yes 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: No 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: 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: In this study protocol, a two-arm non-inferiority randomized control trial is being proposed to compare and validate a FEM semi-automatic algorithm used in designing back braces. The target accrual is 58. All patients will receive both the experimental and control braces and undergo immediate radiographic evaluations. Patients will then be randomized to keep either the experimental or control brace. The primary outcome is the change in Cobb angle of the main curve at two years. Secondary outcomes will be brace failure, quality of life, and immediate in-brace correction. Minor revisions: 1- Line 224: Identify the software that will be used to capture the data. 2- Provide a statistical analysis plan for the quality of life and immediate brace correction outcomes. 3- Line 250 states that the failure rate will be illustrated on a Kaplan-Meier curve. Indicate if the two groups will be compared using inferential statistics. If so, state the testing method that will be used to make this comparison. Will point estimates and 95% confidence intervals be provided? Reviewer #2: Thank you very much for the opportunity to review the submitted article "Optimized braces for the treatment of adolescent idiopathic scoliosis: a study protocol of a prospective randomised controlled trial". The planned study is evaluating a clinically and scientifically important topic prospectively. One concern is related to the low compliance reported for braces for the treatment of scoliosis and possible drop-out. How do the authors plan to avoid this problem or plan to deal with it if it occurs (e.g longer recruitment interval, multi-centric approach)? First, as the study focuses on pediatric/adolescent patients, informed consent must be obtained from participants AND legal representatives. The authors planned to obtain informed consent from patients "and/or parents". Please modify. Furthermore, the authors submitted informations that a conflict of interest is present in some individuals involved in the study. The authors should provide more detailed data on the process of blinding and to assure that individuals with a conflict of interest are not involved in the measurement of clinical outcomes. Please comment. Reviewer #3: Dear author, first of all, I congratulate you on the work you have done. This is a very interesting study regarding improving of braces in the treatment of adolescent idiopatic scoliosis. I think the quality of your paper could be improved in accordance with the following suggestions: Introduction: - Line 75: "To be effective, a brace should ideally be worn 20 to 23 hours a day." Could you please cite a reference/study that support it? - Line 76: "Studies have shown that TLSO are associated with a lower quality of life during the treatment" Could you please explain it? You might find some supporting literature here: PMID 33098493 Inclusion criteria: - why do you exclude premenarchal or no more than 18-year postmenarchal for female patients? There is a particular reason? - Could BMI - or to be more exact heigt and weight - be or not be inclusion criteria of the study? The same question could also regard the familiarity for AIS. ****** 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: Yes: Priv.-Doz. Dr. med. Christian Weber 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. https://doi.org/10.1371/journal.pone.0292069.r001
Revision 1
6 Sep 2023 Author Response Response to Reviewers Manuscript PONE-D-23-11353 Optimized braces for the treatment of adolescent idiopathic scoliosis: a study protocol of a prospective randomised controlled trial. The authors sincerely appreciate the time and effort dedicated to reviewing our manuscript. The manuscript has been revised to address the editor and reviewers’ comments and concerns. Reviewers’ comments are in italics followed by detailed responses in indented paragraphs. All changes referred to below have been made to the revised manuscript and highlighted for easy identification. Responses to Editors Comments: 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 The manuscript was updated to follow PLOS One style requirements. This includes the formatting of affiliations, the capitalization of tittles and the names of figures and files. References have been changed from parenthesis to brackets. Supporting information section has been moved at end of document and reformatted to matched the PLOS One template (https://journals.plos.org/plosone/s/supporting-information). 2. Thank you for stating the following in the Competing Interests section: I have read the journal's policy and the authors of this manuscript have the following competing interests: MC and AG are cofounders and shareholders of Modulate Technologies Inc. HL is a cofounder and shareholder of Spinologics Inc. CEA has a discovery grant from the Natural Sciences and Engineering Research Council of Canada, and a R&D grants from Medtronic paid to the university. SB declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We note that you received funding from a commercial source. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Within this Competing Interests Statement, 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 amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf. The competing statement has been amended to this: I have read the journal's policy and the authors of this manuscript have the following competing interests: MC and AG are cofounders and shareholders of Modulate Technologies Inc. HL is a cofounder and shareholder of Spinologics Inc. CEA has a discovery grant from the Natural Sciences and Engineering Research Council of Canada (NSERC), and a NSERC industrial research grant with Medtronic of Canada paid to the university (outside the scope of the current study). SB declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The NSERC grant with Medtronic was not used to fund this research project. A patent application on the optimization algorithm has been submitted. This does not alter our adherence to PLOS ONE policies on sharing data and materials. [Line 34] The amended competing statement has been added to the manuscript. It states that the NSERC industrial research grant with Medtronic of Canada was not used for this project. It declares a patent application on the optimization algorithm. It also reiterates that this doesn’t alter our adherence to PLOS One policies on sharing. 3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. The Ethics and dissemination section has been removed from the revised version of the abstract. It is now only mentioned in the Methods section of the manuscript. [Line 295] 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. The institutional logo from the original protocol have been removed. [Line 422] 5. 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. The reference list has been reviewed and no retracted paper was found in Pubmed. [Line 336] 6. Please follow the SPIRIT guidelines: re-adapt the whole manuscript, state in a sentence that you follow those guidelines and add its related reference, and add the checklist filled in each part as supplementary material. The Spirit checklist was revised, and missing elements were added to the manuscript and referenced in the Spirit Checklist [Line 421]. A sentence was added to state that we follow Spirit guidelines [Line 132]. Responses to Comments to Authors Point #4: Have the authors described where all data underlying the findings will be made available when the study is complete? In the revised version, we have specified that the anonymize data points will be made available in a public repository for academic purposes. [Line 44] Responses to Reviewers’ Comments Reviewer #1 (minor revision): 1- Line 224: Identify the software that will be used to capture the data. The software used to capture the data was added in the revised manuscript. [Line 259]: “All data, including the patient history, type of brace, radiographs, 3D files and questionnaires will be stored in a Microsoft Access relational database (Microsoft, Redmond, USA).” 2- Provide a statistical analysis plan for the quality of life and immediate brace correction outcomes Details about the statistical analysis plan for the quality of life (SRS-22r scores) and the immediate in-brace correction outcomes were added the Statistical analysis section. [Line 288]: “ For both analysis, the continuous data will be compared between the test and control group with a non-inferior one-sided two-sample t-test, this includes the out-of-brace Cobb angle, the immediate in-brace Cobb angle and the SRS-22r scores. A survival analysis using the log-rank test will be done to analyze the failure rate will be presented on a Kaplan-Meier curve. In case of missing data, a worst-case single imputation will be used. Point estimates and 95% confidence interval will be provided for each result. The statistical analysis will be performed using the R programming language.” 3- Line 250 states that the failure rate will be illustrated on a Kaplan-Meier curve. Indicate if the two groups will be compared using inferential statistics. If so, state the testing method that will be used to make this comparison. Will point estimates and 95% confidence intervals be provided? The statistical plan for the survival analysis (Kaplan-Meier curve) was added. [Line 290] We also confirmed that point estimates and confidence intervals will be provided. [Line 292] Reviewer #2: 1- One concern is related to the low compliance reported for braces for the treatment of scoliosis and possible drop-out. How do the authors plan to avoid this problem or plan to deal with it if it occurs (e.g longer recruitment interval, multi-centric approach)? The dropout rate at our center is low and measures are in place to reduce this occurrence, such as automatic scheduling of follow-up visits and reminders. As for the low compliance, this will be considered part of the treatment, and evaluated in the per protocol analysis with the compliance monitor data. Sentences were added in the Revised manuscript [Lines 280-281] to detail how we plan to deal with this issue. 2- First, as the study focuses on pediatric/adolescent patients, informed consent must be obtained from participants AND legal representatives. The authors planned to obtain informed consent from patients "and/or parents". Please modify. As suggested, the following sentence was added in the Revised manuscript: “The researchers, who have been trained in how to obtain free and informed consent, will obtain this consent from patients and parents/legal representatives.” [Line 140] 3- Furthermore, the authors submitted informations that a conflict of interest is present in some individuals involved in the study. The authors should provide more detailed data on the process of blinding and to assure that individuals with a conflict of interest are not involved in the measurement of clinical outcomes. Please comment. In the Revised manuscript, the following details were added about the blinding process. We also clarified that the outcome assessors will be independent from the research team: “The physician and patient will not be able to identify the braces and thus the group assignation. The outcome assessors will be independent from the research team.” [Line 173] Reviewer #3: Dear author, first of all, I congratulate you on the work you have done. This is a very interesting study regarding improving of braces in the treatment of adolescent idiopatic scoliosis. I think the quality of your paper could be improved in accordance with the following suggestions… We thank this reviewer for the positive appreciation of our study. 1- Introduction: - Line 75: "To be effective, a brace should ideally be worn 20 to 23 hours a day." Could you please cite a reference/study that support it? As suggested, a reference was added in the Revised introduction section, the following sentence was modified to: “To be effective, a brace should ideally be prescribed to be worn more than 18 hours a day, based on the BrAIST Trial recommendations (Weinstein SL, Dolan LA, Wright JG, Dobbs MB. Design of the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST): Spine. 2013 Oct;38(21):1832–41.)”. [Line 84] 2- Introduction - Line 76: "Studies have shown that TLSO are associated with a lower quality of life during the treatment". Could you please explain it? You might find some supporting literature here: PMID 33098493 In the Revised manuscript, we modified the following sentence and a reference to explain that the lower quality of life was due to the psychological burden of the brace treatment: “Studies have shown that TLSO are associated with a lower quality of life (QoL) due to the psychological burden of the brace during the treatment (Cheung PWH, Wong CKH, Cheung JPY. An Insight Into the Health-Related Quality of Life of Adolescent Idiopathic Scoliosis Patients Who Are Braced, Observed, and Previously Braced. Spine. 2019 May 15;44(10):E596–605.; Wang H, Tetteroo D, Arts JJC, Markopoulos P, Ito K. Quality of life of adolescent idiopathic scoliosis patients under brace treatment: a brief communication of literature review. Qual Life Res Int J Qual Life Asp Treat Care Rehabil. 2021 Mar;30(3):703–11.)”. [Line 85] 3- Inclusion criteria: - why do you exclude premenarchal or no more than 18-year postmenarchal for female patients? There is a particular reason? Based on Little et al 2000 (Little DG, Song KM, Katz D, et al. Relationship of peak height velocity to other maturity indicators in idiopathic scoliosis in girls. J Bone Joint Surg Am 2000;82-A:685–93.), the exclusion criteria of more than 18-month postmenarchal was chosen as an indication that skeletal maturity was reached and that the brace treatment would not be appropriate in that group of patients. Premenarchal patient and patient who had their menarche less than 18-month prior are included in the study. In the revised manuscript, the reference to include this relevant point raised by this reviewer [Line 150] - Could BMI - or to be more exact heigt and weight - be or not be inclusion criteria of the study? The same question could also regard the familiarity for AIS. BMI, weight and height were not chosen as inclusion/exclusion criteria in order to maximize the external validity of the study. In the publication resulting from the study, we will present the available data on BMI. We also didn’t use a family history of AIS as inclusion/exclusion criteria in order to maximize the external validity of the study. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0292069.r002
12 Sep 2023 Decision Letter - Filippo Migliorini, Editor Optimized braces for the treatment of adolescent idiopathic scoliosis: a study protocol of a prospective randomised controlled trial PONE-D-23-11353R1 Dear Dr. Hubert, 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, Filippo Migliorini MD, PhD, MBA Academic Editor PLOS ONE Additional Editor Comments (optional): Well done! Regards, Filippo Migliorini Reviewers' comments: https://doi.org/10.1371/journal.pone.0292069.r003
Formally Accepted
3 Oct 2023 Acceptance Letter - Filippo Migliorini, Editor PONE-D-23-11353R1 Optimized braces for the treatment of adolescent idiopathic scoliosis: a study protocol of a prospective randomised controlled trial Dear Dr. Labelle: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr Filippo Migliorini Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0292069.r004

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