Peer Review History

Original SubmissionOctober 28, 2019
Decision Letter - Iddya Karunasagar, Editor

PONE-D-19-28746

Performance of Genotype MTBDRsl V2.0 over 1 the Genotype MTBDRsl V1 for detection of second-line drug resistance: An Indian perspective

PLOS ONE

Dear Professor Singh,

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 reviewer has pointed out the need to revise the manuscript and provide more details on some specific points. One of the Tables also needs improvement

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

We would appreciate receiving your revised manuscript by Jan 12 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Iddya Karunasagar

Academic Editor

PLOS ONE

Journal Requirements:

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

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

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If the need for consent was waived by the ethics committee, please include this information.

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

We wish to thank Mr Akash Ojha and Mr Ashish Soni for their technical help in this study. This study was supported by the grant from Indian Council of Medical Research, Government of India (5/8/5/41/2016/ECD-I) to SS.

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:  NO

4. Please amend either the title on the online submission form (via Edit Submission) or the title in the manuscript so that they are identical.

Additional Editor Comments:

The reviewer has pointed out the need to revise the manuscript and provide more details on some specific points. One of the Tables also needs improvement

[Note: HTML markup is below. Please do not edit.]

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

**********

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

Reviewer #1: N/A

**********

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

**********

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

**********

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: I read with interest manuscript by Rufai et al reporting on the results of a head-to-head comparison of two versions on Hain MTBDRplus in an Indian TB laboratory.

In my opinion design of the study is clear, and conclusions are supported by the results. Relative lack of novelty is one of the problems but bearing in mind study was conducted in high TB incidence settings I don't consider this a major issue.

My recommendations are as follow:

- it would be helpful to know what was the principle of specimens selection, and whether it essentially should be considered a convenience sample - this is necessary to put the results in the context, and decide if these

could be considered generaliseble/expandable to other areas in India.

- I strongly recommend that Table 3 is re-formatted and band patterns are reported as combined patterns with missing WT band and specific mutation bands visible; the way it reports patterns now is extremely confusing and misleading.

- i think expanding on cost issues would be really beneficial in the context of implementation of LPAs for rapid detection of XDR/pre-XDR isolates in India and similar settings. I was really surprised to learn cost of MTBDRplus version 2.0 was significantly higher compared to V1.0 which was not the case in any settings (including high prevalence) I am familiar with. More accurate information is needed on price per test (paper reports cost per kit and it's unclear if it per 12 test box or..?). I would encourage providing more information on prices and call for urgent action from international and more importantly national bodies and considerations on the role of private providers in TB laboratory and diagnostic management in India.

**********

6. 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

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

Reviewers comments Authors Reply

1 Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Thank you very much for the suggestion.

Manuscript has been modified as per PLOS ONE’s style requirements, including those file for naming.

2 Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If the need for consent was waived by the ethics committee, please include this information. Consent was informed and written for samples received for routine TB investigations like smear microscopy, culture and DST Ethics reference number is provided (IHEC-LOP/2018/EF0102).

3. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: NO Funding related text has been removed from the acknowledgement section and will be including in funding statement.

4. Please amend either the title on the online submission form (via Edit Submission) or the title in the manuscript so that they are identical Title on online submission and manuscript has been amended accordingly.

5. It would be helpful to know what was the principle of specimens selection, and whether it essentially should be considered a convenience sample - this is necessary to put the results in the context, and decide if these could be considered generalizable/expandable to other areas in India. The specimens selected in this study were convenience samples and included both pulmonary and extra-pulmonary samples received from different parts of India which were further tested for SIRE DST and second line DST (Rufai et al; Scientific Reports 2018). This study is an extension of the same study. The performance of genotype MTBDRsl V2.0 was evaluated over the Genotype MTBDRsl V1.0) on the aliquots of the same samples. The study has potential to be generalizable to other areas of India.

6. I strongly recommend that Table 3 is re-formatted and band patterns are reported as combined patterns with missing WT band and specific mutation bands visible; the way it reports patterns now is extremely confusing and misleading. Table 3 as well as Table 2 have been formatted as per the suggestions.

7. I think expanding on cost issues would be really beneficial in the context of implementation of LPAs for rapid detection of XDR/pre-XDR isolates in India and similar settings. I was really surprised to learn cost of MTBDRplus version 2.0 was significantly higher compared to V1.0 which was not the case in any settings (including high prevalence) I am familiar with. More accurate information is needed on price per test (paper reports cost per kit and it's unclear if it per 12 test box or.?). I would encourage providing more information on prices and call for urgent action from international and more importantly national bodies and considerations on the role of private providers in TB laboratory and diagnostic management in India. In India the first version (MTBDRsl V1.0) of LPA was available before the launch of Genotype MTBDRsl V2.0 costed ranging from (1389 to 1527) US dollar each kit for 96 tests, while the cost of new version (V2.0) is approximately (1666 to 1944) US dollar each kit of 96 tests (17.3 to 20.2) US dollar per test. The variation in rates are discounted rates based on if it is a government institutions, NGO (not for profit) or private sector.

Attachments
Attachment
Submitted filename: Response_to_reviewers_PONE.docx
Decision Letter - Iddya Karunasagar, Editor

Performance of Genotype MTBDRsl V2.0 over 1 the Genotype MTBDRsl V1 for detection of second-line drug resistance: An Indian perspective

PONE-D-19-28746R1

Dear Dr. Singh,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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.

With kind regards,

Iddya Karunasagar

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All reviewer comments have been addressed.

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

**********

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: Yes

**********

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

Reviewer #1: N/A

**********

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: 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. 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: Reviewer's comments and questions have been adequately addressed so I believe it's now suitable for publication

**********

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

Formally Accepted
Acceptance Letter - Iddya Karunasagar, Editor

PONE-D-19-28746R1

Performance of Genotype MTBDRsl V2.0 over the Genotype MTBDRsl V1 for detection of second line drug resistance: An Indian perspective

Dear Dr. Singh:

I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Iddya Karunasagar

Academic Editor

PLOS ONE

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .