PONE-D-24-58934An Economic Evaluation of the LINKEDin study: An intervention to reduce initial loss to follow-up among tuberculosis patients in South AfricaPLOS ONE

Dear Dr.  Strauss,

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.

Please submit your revised manuscript by Sep 13 2025 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.

We look forward to receiving your revised manuscript.

Kind regards,

Ebenezer Wiafe, PhD, MPharm, Pharm D

Academic Editor

PLOS ONE

Journal Requirements:

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

1.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

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

3. In the online submission form, you indicated that “Data from this study are available to researchers who meet the criteria for access to confidential data and is available from the study PI, Sue-Ann Meehan, available at sueannm@sun.ac.za. Co-investigators are ethically bound to safeguard study materials, including data. Data usage by anyone external to listed co-investigators of the study, requires permission from the Health Research Ethics Committee of Stellenbosch University.”

All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information.

This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval.

4. 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 move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

5. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

6. 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.

7. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

8. 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:

None at the moment.

[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

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

**********

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

**********

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: The paper is well written, with clear language and addressing a very important topic. The study has been conducted at two high-burden TB provinces with differences in the manner that TB services are managed. It is noted that clinically diagnosed patients were not included in the study in KZN province. This study was conducted during a difficult period, during Covid-19 pandemic. The authors have explained how they managed to continue the intervention during this period. The study included a few sites per province. Staffing constitutes 85 % of the total cost. The cost in WC was found to be lower than KZN. WC had more patients overall than KZN which partially explains the cost and also KZN had a lot of laborious operations unlike WC that had automated tasks.

General comments:

I encourage the authors to reflect critically on the different manner that TB services are provided in these 2 provinces. Staff cost is the cost driver. I would like to understand which staff are referred to. Are these TB clerks or general administration clerks. If these are TB appointed staff members, what was the staffing situation in WC during the study and now that probably the situation has changed. The TB programme has been fully integrated into other services. One can say there is no provincial or provincial TB programme in WC. If this is correct, are these results still applicable? How can this intervention be introduced in the context of decreasing number of staff?

Specific comments:

Abstract:

The abstract is good, it provides the summary of the work done, although it does not provide the main findings of the study and the respective costs per province.

Introduction:

Line 25: use the 2024 Global TB Report estimates which is 270,000 for year 2023. Please say something about the provision of TB services overall in these provinces. I am happy with the content covered ion the introduction.

Methods:

Lines 70 - 74 provide eligibility criteria for each province. Please explain why clinical diagnosed patients were not included in KZN. How is the TB notification done in the facilities used for this intervention? Please describe briefly how access to TIER.Net was in KZN.

Discussion:

- The main issue to be added here is the one on staff mentioned as per my general comments and the new working arrangements in the WC province. It is not clear whether these findings are still applicable given the restructuring in WC.

- Additionally, please clarify whether the findings may be generalized within KZN given the differences between facilities even in the same district.

Reviewer #2: This study presents a relevant and well-structured evaluation of interventions aimed at reducing initial loss to follow-up (ILTFU) among TB patients in South Africa. Below are some few comments to improve the manuscript.

Abstract

• State the period the study was carried out

• The two specific interventions evaluated are not described in sufficiently. Briefly outlining what each intervention entailed would provide clearer context for the cost and outcome comparisons.

• While cost drivers are mentioned, the abstract would benefit from including actual cost figures or incremental cost-effectiveness ratios to enhance reader’s understanding of the magnitude of cost differences.

Methods

• Page 11, Line 184: “…1999 individuals were diagnosed with TB were diagnosed…”. Please chek this sentence.

The cost of implementing the LINKEDin intervention in the Western Cape and KwaZulu-Natal

• Page 8, line 121-123: Given that the interest is on incremental or additional costs for implementing the intervention, why do you include the salary of staff(already born by the government) in your staff cost calculations? I thought the best will be to include only additional payments made to the staff, maybe as motivation, due to the intervention.

• Page 9, line 127-128: Please explain further how you collected the data on the level of effort (number of hours per month) that staff spent on each of the intervention activities. Was it collected daily, weekly, monthly etc?

• Page 12: Calculation of ICER – The explanation of the cost calculations lacks sufficient detail. Specifically, more information is needed on the baseline costs before the implementation of LINKEDin.

• It would have been good to conduct a Budget Impact Analysis to inform scale up decision.

Results

Monthly intervention costs

The figures presented in the tables do not match those in the text; therefore, it is necessary to cross-check and ensure consistency between them. For instance:

• Page 13, line 216: I cannot find $14 023.69 in Table 2.

• Page 13, line 221: I cannot find 88% in Table 2.

• Page 13, line 222: I cannot find 4%, 3% in Table 2.

• Page 13, line 227-241: Since cost category proportions relative to total costs are frequently mentioned, it would be helpful to include the percentage contribution of each cost category to the total costs in Table 3

**********

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

Reviewer #2: Yes:Dr Maxwell Dalaba

**********

[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.

An Economic Evaluation of the LINKEDin study: An intervention to reduce initial loss to follow-up among tuberculosis patients in South Africa

PONE-D-24-58934R1

Dear Michael Strauss,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support.

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,

Ebenezer Wiafe, PhD, MPharm, Pharm D

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 #1: All comments have been addressed

Reviewer #2: 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

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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 #1: Yes

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 #1: Yes

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 #1: All issues raised in previous review have been adequately addressed. A clean copy provided a comprehensive document with all tracked changes accepted.

The document with tracked changes reflects changes made to the manuscript. I went through point by point, and I am satisfied with the responses from the authors and the modifications made in the revised manuscript.

Reviewer #2: The authors have adequately addressed concerns raised. They should re through the manuscript and corect typos.

**********

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:Maxwell Ayindenaba Dalaba

**********