Rebuttal letter

July 28th, 2021

Dr. Dominique Heymann, Ph.D.

Academic Editor

PLOS ONE

Dear Editor,

On behalf of all co-authors, I thank you and the reviewers for your time and efforts on revising the manuscript. We now submit the revised text.

I hereby provide responses to the suggestions and, when appropriate, the changes we made. The amendments were indicated in track changes in the original file, as recommended. Below, you will find them with our comments highlighted in red.

Concerning potential competing interests, RMC has received speaker/consultant fees and scientific event grants from Hoffman-La Roche and Takeda. DGC and LWZ have no conflicts of interest to declare. SMR works as an advisor to the Brazilian Program of Inherited Bleeding Disorders (Brazilian Ministry of Health) and received consultancy fees from the Brazilian Ministry of Health. However, this does not alter our adherence to PLOS ONE policies on sharing data and materials. After publication of the final analysis, data can be shared upon request and guarantee of the confidentiality of each participant. Furthermore, this must adhere to the rules of the Brazilian ethical resolutions for the development of research with human beings.

This manuscript has not been submitted to another journal.

I hope the manuscript is now suitable for publication.

Best wishes,

Suely M. Rezende.

 

PONE-D-21-13311

Predictors of the outcome of immune tolerance induction in patients with haemophilia A and inhibitors: the Brazilian Immune Tolerance (BrazIT) Study protocol

PLOS ONE

Dear Dr. Camelo,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The manuscript is interesting. Authors should add information about the statistical methods that will be used for calculating the number that will be enrolled and analyzing the final data sets

We thank the editor for this comment. A sample size calculation was not performed. However, even before the end of the enrollment, we have already included 210 patients. This is the largest cohort of patients with hemophilia A and inhibitors who underwent to ITI to date. We plan to include up to 250 patients.

Please submit your revised manuscript by 5th August 2021. 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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• 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'. It was uploaded.

• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. It was uploaded.

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We look forward to receiving your revised manuscript.

Kind regards,

Dominique Heymann, Ph.D.

Academic Editor

PLOS ONE

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

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

RMC has received speaker/consultant fees and scientific event grants from Hoffman-La Roche and Takeda. DGC and LWZ have no conflicts of interest to declare. SMR works as an advisor to the Brazilian Program of Inherited Bleeding Disorders (Brazilian Ministry of Health) and received consultancy fees from the Brazilian Ministry of Health.

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We added two sentences (in italic) to the Competing Interests part:

RMC has received speaker/consultant fees and scientific event grants from Hoffman-La Roche and Takeda. DGC and LWZ have no conflicts of interest to declare. SMR works as an advisor to the Brazilian Program of Inherited Bleeding Disorders (Brazilian Ministry of Health) and received consultancy fees from the Brazilian Ministry of Health. This does not alter our adherence to all PLOS ONE policies on sharing data and materials. After the publication of the final analysis, the data can be shared upon request and guarantee of the confidentiality of each participant. Furthermore, this must adhere to the rules of the Brazilian ethical resolutions for the development of research with human beings.

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

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. We have changed it accordingly.

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Landsat: http://landsat.visibleearth.nasa.gov/

USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/#

Natural Earth (public domain): http://www.naturalearthdata.com/

After considerations, we have decided to delete the Fig. 1, as well as its citations and caption. Then the previous Fig. 2 turned is now Fig. 1, and its citations and caption were changed.

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. No Supporting Information file was included in our manuscript.

Additional Editor Comments:

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. No changes were made.

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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

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

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

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

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

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: This study protocol is very excellent, well-prepared, and may provide valuable information for management of hemophiliac patient with inhibitor. I really appreciate author's work in this protocol, and I'm eager for the upcoming result of the study.

We thank the reviewer for this compliment.

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Reviewer #1: No

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Attachments

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Submitted filename: methbrazit_rebuttal_letter_01.docx