Peer Review History

Original SubmissionMay 4, 2021
Decision Letter - Wolfgang Miesbach, Editor

PONE-D-21-14425

Effects of replacement therapies with clotting factors in patients with hemophilia: systematic review and meta-analysis

PLOS ONE

Dear Dr. Taype-Rondan, 

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We look forward to receiving your revised manuscript.

Kind regards,

Wolfgang Miesbach, MD

Academic Editor

PLOS ONE

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- https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0233220

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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 is an interesting and well-written paper

The conclusion is not unexpected as the benefits of prophylaxis are well established

This paper has the merit to provide an update on current status of knowledge

Maybe the authors should discuss and compare relative data on SHL and EHL-FVIII

In the title + abstract clearly indicate that only HA is covered

A table with a summary of what information should be collected in future trials could be useful.

Reviewer #2: This is an elegant review and meta-analysis by Taype-Rondan on the effect of clotting factor substitution in patients with haemophilia. The criteria of meta-analyses were met. It would still be interesting to see the authors' outlook on a possible future study design of trials that include the effect of long-acting factor preparation and nonfactor therapy.

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Reviewer #1: No

Reviewer #2: No

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Revision 1

Reviewer #1:

• R1C1: This is an interesting and well-written paper. The conclusion is not unexpected as the benefits of prophylaxis are well established this paper has the merit to provide an update on current status of knowledge.

o We thank you for acknowledging the relevance of this work.

• R1C2: Maybe the authors should discuss and compare relative data on SHL and EHL-FVIII.

o We agree, so we have included the following paragraph in the discussion (right before the “strengths and limitations” subheading:

� “All studies found in our systematic review assessed interventions that used CFCs with standard half-life. CFCs with extended half-life require fewer CFCs administration per week due to their pharmacokinetic properties, which may improve the quality of life of the patients; and also require less use of medical devices, which could help lower the cost of prophylactic treatment. Thus, there is a need of RCTs assessing the use of extended half-life CFCs, which are believed to be as safe and effective as standard half-life CFCs, as WFH 2020 suggests. [6]”

• R1C3: In the title + abstract clearly indicate that only HA is covered.

o We understand that our main results are based on hemophilia A, but this search aimed to find studies in patients with either hemophilia A or B. Although only one study on hemophilia B was found, and this has been described in the table 1 (characteristics of the studies).

• R1C4: A table with a summary of what information should be collected in future trials could be useful.

o We agree that this information is valuable, so we have included the following paragraph in the discussion (right before the “conclusion” subheading):

� “These limitations reflect the need for high-quality RCTs that compare different doses of prophylactic treatment (low, intermediate, or high doses) or extended half-life vs standard half-life CFCs. Which assess clinically relevant outcomes (mortality, ABR, ABJR, joint disease, joint status, pain, current health status-HRQol, activities, employment, educational attendance, resource utilization) [43], and with enough follow-up period to assess these outcomes (ideally more than one year).”

Reviewer #2:

• R2C1: This is an elegant review and meta-analysis by Taype-Rondan on the effect of clotting factor substitution in patients with haemophilia. The criteria of meta-analyses were met.

o We thank you for your kind comment.

• R2C2: It would still be interesting to see the authors' outlook on a possible future study design of trials that include the effect of long-acting factor preparation and nonfactor therapy.

o We agree that this information is valuable, so we have included the following paragraph in the discussion (right before the “conclusion” subheading):

� “These limitations reflect the need for high-quality RCTs that compare different doses of prophylactic treatment (low, intermediate, or high doses) or extended half-life vs standard half-life CFCs. Which assess clinically relevant outcomes (mortality, ABR, ABJR, joint disease, joint status, pain, current health status-HRQol, activities, employment, educational attendance, resource utilization) [43], and with enough follow-up period to assess these outcomes (ideally more than one year).”

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Wolfgang Miesbach, Editor

Effects of replacement therapies with clotting factors in patients with hemophilia: a systematic review and meta-analysis

PONE-D-21-14425R1

Dear Dr. Taype-Rondan,

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,

Wolfgang Miesbach, MD

Academic Editor

PLOS ONE

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

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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

**********

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

Reviewer #2: 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 #2: 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 #2: 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 #2: (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 #2: No

Formally Accepted
Acceptance Letter - Wolfgang Miesbach, Editor

PONE-D-21-14425R1

Effects of replacement therapies with clotting factors in patients with hemophilia: a systematic review and meta-analysis

Dear Dr. Taype-Rondan:

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. Wolfgang Miesbach

Academic Editor

PLOS ONE

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