PONE-D-22-11504Frequency of complications in a cohort of patients diagnosed with hemophilia A or hemophilia B receiving prophylactic treatment at a health care institution in Colombia: Retrospective noninterventional studyPLOS ONE

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” yes: Reyes JM, Lourdes M and Castano N are paid employees of Pfizer Colombia. Juan David Wilches-Gutierrez, Diana Rocio Arias-Osorio are paid employees of IPS-Especializada. Andres Gaviria-Mendoza, Natalia Castaño-Gamboa, Luis Fernando Valladales-Restrepo, Manuel E. Machado-Duque and Jorge Machado-Alba are paid employees of Audifarma SA. Harrison David Ospina-Arzuaga do not have any conflict of interest.”

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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: Partly

Reviewer #2: Partly

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: No

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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: In their manuscript authors followed a retrospectice cohort, trying to define outcomes of therapy (prophylaxis/ on demand, plasma deriverd/ recombinanat coagulation products) eg: bleeding, inhibitor formation among patients treated between 2012-2019. The manuscript is well written yet showes no novelty and could be improved by additional dAZta collection (eg: mutation type, if available, additional data re emicizumab tretament (approved after 2019). Authors are advised to resubmit into na hemophilia specific journal

Reviewer #2: This manuscript gives an overview a substantial group of patients receiving prophylaxis in Colombia. These real world data give important information about the effectiveness and complications of prophylactic treatment.

I have some suggestions to improve the manuscript.

First of all, for readers not familiair with the Coagulopathies Program of IPS-E (such as myself) it would be helpful to give a short background about te program, who is included, will this lead to selection bias influencing the data?

Minor suggestions:

- I think the proportion of patients receiving plasma-deriverd products is rather high, although lower than 50%. Using the words 'mainly' and 'most frequently' is misleading with such a small difference.

- I would suggest altering the term 'antihemophilic factor' into 'substitution therapy / clotting factor replacement

- bivariate analysis: which variables were investigated?

- Table 1: The column % is not always a percentage

- Table 1 and 2: dose (IU per week) would be more informative if changed into dose/kg/wk

- Please provide data about the number of exposure days before inhibitor develpment occurred

- in the patients with the anaphylactidc reaction, both haemophiliia B patients, was this associated with inhibitor development?

- Table 2: under 'weekly factor dose', what dose ;use of recombinant factors' mean?

- Table 3: 'total of follow up ' what does this mean?

- Table 3: why are patients with bruising admitted to the hospital?

Reviewer #3: General comments

- The topic is important, however, the paper needs revision and further editing.

- All comments are mentioned on the text of the paper.

Specific comments

Title: the suggested title is " The Frequency of complications in a cohort of patients with hemophilia A and B receiving prophylactic treatment in Colombia: a retrospective non-interventional study".

Introduction:

- Line 72; Hemophilia A and B are rare diseases worldwide and not only in Colombia.

- Line 99: Provider needs to be replaced by Institution

Materials and methods:

- Line 110: Does this statement mean that authors stop following patients when they develop inhibitors? If Yes, Why they did not follow them?

- Line 133: Authors need to clarify what they mean by trauma as high percentage of patients had trauma (68%, Table 4).

Results:

- Line 173: the statement needs to be changed as mentioned in the comments.

- The titles of most Tables need to be changed (the suggested titles are mentioned on the manuscript).

- Table 4: This table needs to be reviewed and many details can be mentioned in the text instead, e.g. types of bleeding, trauma and surgeries.

- Line 231: Bivariate analysis; This is very important, it needs to be put in a Table, and only the important findings can be written in the text

Discussion:

- Line 312: Reference 16 needs to be added.

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Reviewer #1: No

Reviewer #2: Yes: L.F.D. van Vulpen

Reviewer #3: Yes: Meaad Kadhum Hassan

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Attachments

Attachment

Submitted filename: PONE-D-22-11504_R.pdf

Attachment

Submitted filename: Comments.pdf

The frequency of complications in a cohort of patients diagnosed with hemophilia A and hemophilia B receiving prophylactic treatment in Colombia: a retrospective noninterventional study

PONE-D-22-11504R1

Dear Dr. Machado-Alba,

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. Please note that one of the reviewers has two minor comments (refer to attached file) - you can make the changes when you check the draft.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Roza Chaireti

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 #2: 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: I Don't Know

Reviewer #3: Yes

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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 #2: 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 #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: No furter comments, previous comments are adequatly adressed. This manuscript gives a nice overview of the haemophilia patients receiving expensive treatment in a low resource country.

Reviewer #3: Most of the comments were done by the authors. Only 2 comments (in the attached file. minor) need to be corrected.

These are present on the attached file.

Regards

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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 #2: No

Reviewer #3: No

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