PONE-D-24-06032Introducing BPaL: experiences from countries supported under the LIFT-TB ProjectPLOS ONE

Dear Dr. Wares,

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We look forward to receiving your revised manuscript.

Kind regards,

Shahriar Ahmed, MBBS, MHE, MPhil

Academic Editor

PLOS ONE

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2. Thank you for stating in your Funding Statement: "Activities under the “Leveraging Innovation for Faster Treatment of Tuberculosis (LIFT-TB)” project in the seven countries and at KNCV TB Foundation, the Netherlands and the International TB Research Center, Republic of Korea, global levels, were supported by funding from the Korea International Cooperation Agency (KOICA), Republic of Korea and the TB Alliance (TBA), the United States of America. The following authors received partial salary support via the LIFT-TB project: DFW; MM; VM; MQ; AS; IK; SNC; UG; JSL; J-KJ; and AG. KOICA had no role in the operational research study design, data collection and analysis, decision to publish, or preparation of the manuscript. As lead co-ordinating partner in the LIFT-TB project, TBA did play a role in the operational research study design, data collection and analysis, decision to publish, and preparation of the manuscript.  

KOICA https://www.koica.go.kr/ TBA. TB Alliance | Putting science to work for better, faster TB cures."

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Additional Editor Comments:

Thank you for submitting your well written manuscript to this journal. We believe that the comments from the reviewers are very constructive, should be fairly easy to respond to, and will improve the overall impact of the manuscript. We look forward to receiving the revised manuscript soon.

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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: N/A

Reviewer #2: N/A

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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: No

Reviewer #2: No

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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: Thanks to the authors for their research paper titled “Introducing BPaL: experiences from countries under the LIFT-TB Project” which describes the processes, the challenges, and interim results of the introduction of the BPaL regimen under OR conditions in 7 countries. This was a timely step taken under operational research conditions to test/validate the study results observed in a previous study named Nix-TB study. The authors have presented the processes, challenges and interim results of their study very well.

The manuscript is technically sound and the data supports the conclusions.

Despite their efforts the authors couldn’t make all data underlying in the findings their manuscript fully available as the data cannot be shared publicly because of legal ownership restrictions. All data is the property of the respective countries. The authors have access to the respective database via data sharing agreements signed with the MOH of each country and the data underlying the results can be made available if permission is granted by the respective MOH for researchers who meet the criteria for access to confidential data.

The authors may consider the below suggestions for their paper:

Background: The WHO recommendation on shorter 9-month treatment regimen (STR) was made in 2016 (https://www.who.int/news/item/12-05-2016-rapid-diagnostic-test-and-shorter-cheaper-treatment-signal-new-hope-for-multidrug-resistant-tuberculosis-patients) but in the background (last sentence) it is mentioned - “Since 2018, the WHO has recommended that for certain MDR/RR-TB.......”

Table 3: Please check the figures and their totals for correctness e.g. there are differences in Philippines between the “number of patients with end of treatment outcome evaluation in REDCap (93)” and “End of treatment success (84)” – is there is any reason why only 84 were evaluated for treatment success while 93 had end of treatment outcome data? Please check the totals (at the bottom row [(82+43+82+34+40) / (86+50+84+39+40) = 279/299 = 93.3%] of the last column with “End of treatment success (%)” which is shown 280/308 (90.9%)

Table 4: BPaL safety data showing the numbers with adverse event types but not presenting the numbers requiring decreasing the dose or stop of LZD and the number of patients discontinued treatment. Please specify what types of treatment modifications (dose of Lzd decreased or Lzd stopped or full treatment regimen discontinued?) accounted under “adverse events leading to treatment modification (AELTM)”

Discussion (the two key changes are): recommended age of patients for the 6-month BPaLM regimen is 14 years and above (it is mentioned in the manuscript ≥15 years) and previous exposure to Bdq, Pa and Lzd defined as 1 month or more (in the manuscript >1-month exposure).

Reviewer #2: The manuscript reports on "Introducing BPaL: experiences from countries supported under the LIFT-TB Project". It is well written, clear and comprehensive. The experience from the BPaL operational research - including on the processes, lessons learned, challenges, mitigation measures implemented and the interim results - are all important to NTPs, in-country and international stakeholders. The interim results (excellent treatment outcome) could contribute to building confidence and improve uptake of the 6-month regimen being implemented in programmatic conditions.

I agree and appreciate the research team's decision to "assisting countries programmatically introduce the

BPaL-based regimens for a much wider group of DR-TB patients as soon as possible, whilst wrapping

up the BPaL OR reported on here in line with the WHO's revised recommendation/guidance in 2023 and 2024". Targeted technical assistance and advocacy would be critical to accelerate uptake and transitioning to the best available treatment regimens.

Minor comments

- I would suggest revising the term "prove" as OR mayn't be the best option to do so (abstract and 5th para - background).

- Page 11 1st para, line 3 (Background) - delete "each year" as the year is already specified (2022) in the same sentence.

- Provide the data on the number of patients who discontinued treatment due to SAEs rather than saying "few" (abstract, and Result page 22). This information (if available) could be added to Table 4 (page 22) as well.

- Please clarify why the interim results from Myanmar and Ukraine were not available in Q2/2024 (253 patients? is this related to the contexts in the countries? do you anticipate different outcome?

- In Vietnam, was it due to "very prolonged impact of the COVID-19 pandemic..." or late initiation of the pandemic (unlike in most other countries, the pandemic started in Vietnam in 2021)?

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Reviewer #1: No

Reviewer #2: Yes: Mohammed Yassin (MD, MSc, PhD),

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PONE-D-24-06032R1Introducing BPaL: experiences from countries supported under the LIFT-TB ProjectPLOS ONE

Dear Dr. Wares,

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.

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

I would like to congratulate the authors for this very well written manuscript and timely submission of the revised version. There is just one minor comment left to be addressed from reviewer 2. Please address the comment and we will be happy to move forward with final decision. 

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Please submit your revised manuscript by Oct 19 2024 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,

Shahriar Ahmed, MBBS, MHE, MPhil

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:

Thank you for submitting the revised version addressing the comments. This manuscript is now almost suitable for acceptance. There is minor comment by reviewer 2 that still needs to be addressed and it should not take more than a few hours of time. Please address the comment and we will be able to mover forward with a decision.

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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 #1: All comments have been addressed

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 #1: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: N/A

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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 #1: (No Response)

Reviewer #2: 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 #1: (No Response)

Reviewer #2: 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 #1: The authors have addressed my comments raised in a previous round of review which are accepted by me.

Reviewer #2: Pease add the information on Vietnam's COVID timeline as the epidemic started late (in 2021) compared to other countries as this might have contributed to the difference in addition to what you have mentioned.

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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: Yes: Dr Mohammed A Yassin

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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.

Introducing BPaL: experiences from countries supported under the LIFT-TB Project

PONE-D-24-06032R2

Dear Dr. Wares,

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.

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Kind regards,

Shahriar Ahmed, MBBS, MHE, MPhil

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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