PONE-D-23-42050Cost-effectiveness and benefits of perinatal health interventions in high income settings: a protocol for a systematic review of economic evaluationsPLOS ONE

Dear Dr. Haile,

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.

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Dear Respectable AuthorsThe review is complete. Please send us the revised version as soon as possible. Please respond to all review comments point by point and highlight changes through the text.Cheers

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Please submit your revised manuscript by Apr 20 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'.
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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,

Morteza Arab-Zozani, Ph. D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Partly

Reviewer #3: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

Reviewer #2: No

Reviewer #3: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Publication of protocols and analysis plans is becoming common practice quite rapidly and I feel this is a good development in the light of open science, although the protocol of a review may bear less relevance than the protocol of a planned clinical study. Especially since the protocol was also registered in PROSPERO.

Apart from this, there is quite some room for improvement in the current manuscript, which are summed up below.

- To begin with, I would like to point out the paper series published by a Dutch research group on performing reviews of economic evaluations – papers number 1 and 3 may offer some helpful suggestions: How to prepare a systematic review of economic evaluations for informing evidence-based healthcare decisions: a five-step approach (part 1/3) - https://pubmed.ncbi.nlm.nih.gov/27805469/

- The aim of the review is, reading from the abstract: ‘to comprehensively assess the economic evidence for such interventions in high-income countries’. The authors plan to do this by extracting outcomes such as cost-effectiveness, cost-utility and cost-benefit from the included studies. What is not clear from this paper though is how the authors plan to summarize outcomes. It is to be expected that there will be a large variety of interventions, populations, and outcomes found in the included papers. How do the authors plan to summarize results of a study into the cost-effectiveness of prophylactic aspirin in all pregnant women to prevent complications such as pre-eclampsia, and a study into the cost-benefits of intensified obstetric care to prevent complications during delivery? The authors state that ‘due to the challenges in pooling cost and effectiveness/benefits/utility data from different interventions, countries/settings or derived using different methodological approaches, a narrative and tabular summary of the results will be made’. I agree, pooling will not be possible at all probably, but then the only thing that can be done is presenting enormous tables (because the authors want to include practically everything that has something to do with costs and pregnancy) with no way or structure to draw overall conclusions from these. The idea to perform ‘subgroup analysis based on the type of economic evaluation … for better description of the most cost-effective and beneficial perinatal health interventions’ can probably only help when cost per QALY (or maybe DALY – but not often seen in HIC) are reported, otherwise one cannot compare between interventions/populations etc. Also, it does not make sense to include cost studies as they are not, strictly speaking, ‘economic evidence’ which would enable decision makers to prioritize an intervention. In my opinion, the authors are very ambitious, too ambitious. It would help if there was already a preliminary run of the search terms to see how many hits there are – probably hundreds to thousands?

- From the introduction and discussion sections, it does not become too obvious yet why the researchers chose the high income setting to address the SDG. It is quite well known that the larger part (maybe as much as 90%) of the burden of maternal and child morbidity and mortality lies outside of the high income setting. Although the authors make an argument that also in high income settings there is large differences between population groups, I am not convinced that this systematic review will truly contribute to attaining the SDGs. Would there be a way to extend findings and conclusions in this review to the LMIC setting, that is, when interventions are found to be cost-effective in HIC, may they also be cost-effective in LMIC? Would the review deliver recommendations for LMIC as well? If that were the case, there would be more relevance of this study in relation to the SDG.

- The sub-section on comparisons (p10) puzzles me greatly – I do not understand what is said here.

- English language is a problem – even a non-native speaker as myself spotted a large amount of typos and incorrect sentences. Examples (did not list them all):

o P3 lines 55-56 -> with an estimated 2 million…. occur annually (occurring)

o P3 lines 57 -> SDGs target 3.2 aim to…. (aims to)

o P9 line 152 -> First, two reviewers will first (2x first)

o P9 line 172 -> neonatal mortality, preterm, low birthweight (preterm birth)

o P10 lines 177-178 -> i) no interventions for these routine perinatal health care interventions (I don’t understand this sentence at all)

o P10 lines 189-190 -> we will include …. will be included (phrasing is bad)

o P10 line 196 -> comprise (comprising)

Please run a very thorough check of the language and make sure it reads well.

Reviewer #2: This study reports on “Cost-effectiveness and benefits of perinatal health interventions in high income settings: a protocol for a systematic review of economic evaluations”. The topic is of interest.

- Some suggestions are listed below, which may be useful to the authors as they seek to revise their manuscript.

General comment:

I invite the authors write the paper in the “past tense”.

Abstract

Methodology: Please report the year, the study was conducted, and time framework the studies covered.

Introduction

-This section is written well and sounds good.

Methods

-Like abstract, please report the year, the study was conducted, and time framework the studies covered.

-How was the quality of the studies scored?

-The Table of quality assessment is missing.

Results

-The result section is missing.

Discussion

-This section should rewrite and improve.

-This section is too short.

-The conclusion is missing.

-The limitations and strengths section is missing.

Reviewer #3: The authors have undertaken a significant endeavor to analyze the economic efficiency of health interventions directed at perinatal morbidity and mortality in high-income countries. Such work is indeed praiseworthy and necessary, as it is in line with the Sustainable Development Goals, addressing profound clinical and economic issues. The manuscript's in-depth examination of the disparities in adverse perinatal outcomes across socioeconomic strata is critical for a nuanced understanding of this global issue.

The manuscript notably identifies a significant gap in the literature concerning comprehensive economic evaluations of perinatal health interventions. This point is particularly impactful, with potential to greatly influence policy-making for enhanced health outcomes. The focus on contemporary studies post-2010 is appropriate given the progressive nature of healthcare interventions and economics, and the reviewer supports this approach. Nevertheless, the choice to exclude older studies should be substantiated with a strong rationale, as it could omit historical data essential for trend analysis. The authors are thus encouraged to elaborate on this choice and suggest ways to balance the need for current data with the value of historical trends.

While the manuscript adeptly handles high-income country scenarios, its findings' applicability to low- and middle-income countries (LMICs) is not discussed. Given the disproportionate burden of perinatal morbidity and mortality in these settings, the authors should consider the transferability of effective interventions from high-income contexts to LMICs, taking into account the differences in resources and healthcare systems.

The manuscript would gain depth by addressing the possible limitations inherent in its current scope, especially concerning the exclusion of pre-2010 data. Including a discussion about the trends in healthcare costs, the effects of historical health policies, and the longevity of intervention outcomes would greatly contribute to understanding the current economic milieu of perinatal health interventions.

In conclusion, the manuscript provides a comprehensive and well-organized study protocol that adeptly addresses a significant health issue, commendably aligning with the objectives outlined in the Sustainable Development Goals, particularly those targeting profound clinical and economic challenges. While the manuscript currently does not include the results of the study, incorporating such findings in the future would significantly enhance the value and richness of the paper. Nonetheless, as it stands, the protocol offers a robust framework for the investigation of the economic efficiency of interventions aimed at improving perinatal health outcomes in high-income countries. It is advisable for the authors to expand their discussion to incorporate the issues that have been highlighted. Delving deeper into these areas would not only broaden the manuscript's scope and deepen its analytical insights but also elevate its significance and contribution to the wider academic and policy-making discourse.

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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: No

Reviewer #3: No

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PONE-D-23-42050R1Cost-effectiveness and benefits of perinatal health interventions in high income settings: a protocol for a systematic review of economic evaluationsPLOS ONE

Dear Dr. Haile,

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 Jun 29 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,

Miquel Vall-llosera Camps

Senior Staff 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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #3: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #3: 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 #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have made a substantial effort to improve their manuscript and have taken the suggestions provided by the reviewers to heart. I have one comment still with regard to the definition of the comparators give the updated scope of the review: the authors have chosen to not include partial economic evaluations in their planned review anymore, which I feel is a sensible decision. However, since a full economic evaluation would always include a comparative element (see also the clear definitions in this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424074/ ) - the fourth comparator on p10 of the clean manuscript, stating 'No comparators: Economic evaluations focusing solely on the costs of perinatal health interventions without specific comparators.' - is not a valid comparison here - this could only be a relevant thing to study when partial economic evaluations would be included. So this 4th option should be removed from the list.

Last remark: given that scope and search terms have been updated, will this also be aligned in the prospero protocol, that is, will prospero be updated accordingly?

Reviewer #3: This review is expected to notably affect healthcare practices by summarizing the financial impacts and benefits of perinatal interventions, aiding in the optimization of strategies to avert negative perinatal outcomes.

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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: Yes: Antoinette D.I. van Asselt

Reviewer #3: Yes: Abu Ahmed

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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.

Cost-effectiveness and benefits of perinatal health interventions in high-income settings: a protocol for a systematic review of economic evaluations

PONE-D-23-42050R2

Dear Dr. Haile,

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.

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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,

Dr. Cristóbal Cuadrado N.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for adequately addressing the commentaries and suggestions of the reviewers and editors. The manuscript is now ready to be accepted for publication.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I would like to thank the authors for their respectful responses, I have no further comments on the revised version

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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

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