-->PONE-D-26-01167-->-->Cost-effectiveness of bubble continuous positive airway pressure in treating severe pneumonia and hypoxaemia in under-five children in Ethiopia-->-->PLOS One

Dear Dr. Negasa,

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 manuscript addresses a topic of high clinical and public health relevance, as it evaluates the cost-effectiveness of two procedures for the management of severe pneumonia in children under five years of age, with potential implications for child survival and decision-making in settings such as Ethiopia. Overall, the study has a valuable conceptual foundation and addresses an important issue; however, it requires strengthening in several methodological, reporting, transparency, and scientific argumentation aspects before it can be considered ready for publication.

First, the study would benefit from greater conceptual and methodological clarity . It is essential to define severe pneumonia  precisely according to recognized criteria, ideally based on WHO standards, including danger signs and oxygen saturation below 90%. The study period , the type and recency of the published sources used, and the analytical model applied should also be described more clearly. In addition, the manuscript should provide a stronger justification for the comparability of the two interventions, better describe the clinical trial or source evidence used, and explain more explicitly the assumptions underlying the cost-effectiveness analysis.

Second, the manuscript requires greater transparency in the presentation of data, tables, and model assumptions . The sources used in Table 1 should be clarified by distinguishing which parameters were derived from randomized controlled trials and which were based on assumptions. It would also be highly valuable to include a supplementary file  presenting oxygen calculations, model equations, and other technical details necessary to improve understanding and reproducibility of the analysis. Table numbering should be corrected, and the base-case results should be organized into a dedicated table.

Third, the introduction requires substantial revision . At present, it appears weak in structure, insufficiently referenced, and lacking important contextual elements. Key concepts such as hypoxia should be clearly defined, and the magnitude and severity of the problem should be presented more robustly. The Ethiopian context should be explicitly introduced in the background section. In addition, the references should be carefully reviewed to ensure that each citation appropriately supports the claims made. The rationale for the use of bCPAP should also be better developed, including its origin, current recommendations, validation in Ethiopia, whether it has been incorporated into national clinical guidelines, and how it relates to WHO and Ethiopian Ministry of Health recommendations.

Fourth, the methods section  lacks important details regarding both the implementation of the interventions and the structure of the decision model. For example, the manuscript should clarify how and when patients were reassessed, whether blood oxygen saturation was measured, whether both groups had the same clinical severity at admission, which components were included in medical costs, whether intravenous antibiotics were administered in parallel with the interventions, why average length of hospital stay was not considered, and what happened to children initially treated as outpatients who later required admission. The absence of certain clinical branches in the decision tree, such as medical ventilation after treatment failure, should also be justified. Likewise, the manuscript should specify more clearly the type and number of hospitals included in the analysis.

Fifth, the results section  should be presented with greater clarity and completeness. At present, it appears too brief and somewhat imprecise. The authors are encouraged to revise the tables that contain empty cells, expand the presentation of relevant descriptive variables such as age, sex, and residence, and organize the main findings more clearly to facilitate interpretation.

Sixth, the discussion section  requires major strengthening. It should focus more directly on the study findings and avoid conflating clinical effectiveness with cost-effectiveness. A deeper and better-justified interpretation of the findings is needed, particularly regarding the apparently high cost-effectiveness of strategies such as nurse support provided by telephone. The discussion should engage more critically with the existing literature, provide a stronger explanation of the results, and offer a more convincing justification for the appropriateness and implications of the analysis.

Finally, several additional technical improvements  are recommended to enhance the robustness of the manuscript: updating the GDP value to 2025, expanding the probabilistic sensitivity analysis to 10,000 iterations, and considering a five-year scenario analysis to better estimate long-term DALYs, since the current approach may underestimate the value of the intervention.

In summary, the manuscript has merit, relevance, and publication potential; however, it requires substantial revision to improve its methodological consistency, analytical transparency, argumentative depth, and overall scientific writing quality. With these revisions, the study could be significantly strengthened and brought closer to a publishable standard.

Please submit your revised manuscript by Apr 26 2026 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.

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Oriana Rivera-Lozada de Bonilla

Academic Editor

PLOS One

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Reviewer #1: Partly

Reviewer #2: Partly

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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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: Dear Authors,

Good study with high policy relevance for Ethiopia. To strengthen for publication:

Key improvements needed:

Define severe pneumonia using WHO criteria (danger signs + SpO2<90%)

Add 5-year scenario analysis for long-term DALYs (currently underestimates value)

Clarify Table 1 sources (RCT vs. assumptions) + create Supplementary File 1 (oxygen calculations, model equations)

Update GDP to 2025 (~$1,120) + extend PSA to 10k iterations

Fix Table numbering (base-case results need dedicated Table 3)

Methods conceptually strong minor transparency fixes will make this publication ready.

Happy to discuss further.

Best regards,

Reviewer #2: The manuscript is very good and intends to address the cost effectiveness analysis of the two procedures for the care of severe pneumonia which will have immense contribution for the clinical practiceband public health significance in improving the life of children and fostering the survival of under five children. The following are our comments.

1.Whyv the second author become the corresponding author and If so why he is not ordered first?

2.The abstract is good. But the background lack place E.g. Ethiopia. The methods have no study period and avoid bracketing. It also fails to mention the models used to evaluate it why? And lacks completeness. Revisit it. The result is good but needs further refinement and the conclusion is short.

3.Introduction is very weak and weakly referenced. First, it Fails to define hypoxia. Second, weaklybotlrganized and hade missing link.Third, the magnitude and the severity is weakly stated. Forth, did refrence number three works for the three that is the South Asia, Subject saharan Africa and Ethiopia meaning Gebre is an Asian and African and Ethiopianand have defined it?

-Likewise, when was both interventions begin, is that similar, for how long does they work, bCPAP recommendation, whatv is wrong with the WHo recommendation?, Who recommended bCPAP, when, why, how, by whom, for whom, in what settings, is that validated in ethipoa and putted in the clinical guideline? What are the recent recommendations busy wHO and Ministry healthbof Ethiopia and what remains unanswered and is this the best way to estimate the cost effectiveness analysis and why?

4.Methods. It is relatively good but it is incomplete for some issues.

-The study period is missed . Likewise, you stated that you have used published literatures. Are they up to date?

-bCPAP is incompletely presented E.g when was the reassememt done for the admitted underfive child?

--Are both procedures comparable?

-How was confounding factors in the trial? What type of specific RCT?

-On the decision tree model, why there is no direct medical ventilation after treatment failure?

-The components of medical costs are not described?

-Is the child at the same severity of (severe pneumonia) illness at admission for both interventions?

-Is there blood oxygen measurement in the assessment?

-What are those general hospitals and their numbers and are they not on trnsition to Specialized or compherensive hospitals?

-Is the diagnosis at OPD or inpatient and who diagnosed the under five children? This is also true for the discharge diagnosis?

-Is that parallel treatment with the IV antibiotics and the interventions or not?

-Why didn't you consider the mean hospital stay for both?

-How many of these underfive children were treated at OPD and failedand then admitted?

-What are the assumptions of cost effectiveness analysis? And are they complete?

-How quality was the data?

-What is rhe assumptions behind the analysis and convince your reader for the appropriateness of the analysis?

-Some lacks reference.

5.Results

-It is short not clear, brief and accurate.

-Why some columns of the table are empty? E.g Table 1.

-What about the other variables e.g Age, sex, residence?

6.Discussion

-It is Inadequate and fails to address the objective of the study well. In addition, the clinical effectiveness is different from cost effectiveness, therefore, focus on your findings. Likewise, why advice over phone to the nurse resulted in to high cost effectiveness needs fetail explanation. Again, itbis inadequately written, short, weakly explained and justified as well as referenced. Focus on the objective of the study. I think the researchers have no full knowledge about both the interventions and failed to read the guideline.

Regards,

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Reviewer #1: Yes: Emna ben jemia

Reviewer #2: No

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Attachments

Attachment

Submitted filename: REVEWING ATTACHEMENTS.docx

-->PONE-D-26-01167R1-->-->Cost-effectiveness of bubble continuous positive airway pressure in treating severe pneumonia and hypoxaemia in under-five children in Ethiopia-->-->PLOS One

Dear Dr. Negasa,

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 revised manuscript has substantially improved in terms of conceptual clarity, model description, comparability of the interventions, transparency of cost inputs, and discussion of assumptions and limitations. The use of a decision-tree model, clearer definitions of severe pneumonia and hypoxaemia, reference to the CHEERS 2022 reporting standards, and an expanded sensitivity analysis strengthen the manuscript.

The conclusions are adequately supported by the results presented, particularly the reported ICER of approximately US$139.5 per DALY averted and the finding that bCPAP remains cost-effective under the stated willingness-to-pay thresholds. The study provides relevant economic evidence to inform policy and implementation decisions in Ethiopia and other low-resource settings.

Before acceptance, a few minor issues should be addressed: the manuscript should undergo final proofreading for style and grammar; terminology such as hypoxaemia/hypoxemia should be used consistently; the number of probabilistic sensitivity analysis iterations should be consistent across the Methods, Results, and figures; and the rationale for using 2022 as the cost year and GDP reference year should be stated consistently throughout the manuscript.

Recommendation: minor revision. The manuscript is scientifically relevant and methodologically acceptable for PLOS ONE, provided that these remaining editorial and consistency-related issues are corrected.

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

Please submit your revised manuscript by Jul 03 2026 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.

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-->

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Oriana Rivera-Lozada de Bonilla

Academic Editor

PLOS One

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Reviewers' comments:

Reviewer's Responses to Questions

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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 #3: Yes

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

Reviewer #3: Yes

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Reviewer #3: Yes

**********

-->5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #3: Yes

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-->6. Review Comments to the Author

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Reviewer #3:  Overall assessment

This manuscript addresses an important public health and health economic question in a resource-limited setting. The study evaluates the cost-effectiveness of locally made bubble continuous positive airway pressure (bCPAP) compared with WHO-recommended low-flow oxygen therapy for under-five children with severe pneumonia and hypoxaemia in Ethiopian general hospitals.

The revised manuscript has substantially improved in conceptual clarity, model description, intervention comparability, cost-input transparency, and discussion of assumptions and limitations. The use of a decision-tree model, clearer definitions of severe pneumonia and hypoxaemia, reference to CHEERS 2022 reporting, and expanded sensitivity analysis strengthen the manuscript. The findings appear relevant for policy and implementation decisions in Ethiopia and similar low-resource settings.

The conclusions are generally supported by the presented results, particularly the reported ICER of approximately US$139.5 per DALY averted and the finding that bCPAP remains cost-effective under the stated willingness-to-pay thresholds.

Comments for the authors

• Scientific contribution: The topic is timely and relevant. The manuscript provides useful economic evidence to complement the existing clinical trial evidence on bCPAP in Ethiopia. This is valuable because adoption of bCPAP in national paediatric care requires not only clinical effectiveness data but also clear cost-effectiveness evidence.

• Methods and transparency: The methods are now clearer, particularly regarding the decision-tree structure, the short-term time horizon from admission to discharge or death, the comparability of care between groups, and the exclusion of long-term costs and outcomes. The addition of technical details and the CHEERS 2022 checklist is appropriate and improves reproducibility.

• Interpretation: The discussion is improved and more focused on the study objective. The manuscript appropriately acknowledges that cost-effectiveness findings should be interpreted in the context of implementation requirements, including trained staff, oxygen availability, monitoring, and facility readiness.

Minor issues to address before acceptance

1. The manuscript should undergo careful final proofreading to correct typographical errors, grammatical issues, and awkward sentence structures. Examples include inconsistent spelling of hypoxaemia/hypoxemia and minor wording problems in the Methods and Discussion sections.

2. Please ensure consistency between the Methods and Results regarding the number of probabilistic sensitivity analysis iterations. The Results and figures report 10,000 iterations, while the Methods section should also consistently state 10,000 iterations if that is the final analysis.

3. The rationale for using 2022 as the cost year and GDP reference year is acceptable, but it should be stated consistently in the abstract, methods, results, and discussion to avoid confusion.

Recommendation

Minor revision. The manuscript is scientifically relevant and methodologically acceptable for PLOS ONE after final proofreading, consistency checks, and removal of formatting artifacts. The remaining issues are mainly editorial and consistency-related rather than fundamental methodological concerns.

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Reviewer #3: No

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Attachments

Attachment

Submitted filename: PLOS_ONE_Peer_Review_Comments_PONE-D-26-01167R1_clean.docx

Cost-effectiveness of bubble continuous positive airway pressure in treating severe pneumonia and hypoxaemia in under-five children in Ethiopia

PONE-D-26-01167R2

Dear Dr. Abdi Gari Negasa,

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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Oriana Rivera-Lozada de Bonilla

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PLOS One