Dear Dr. Schulten,

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.

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

ACADEMIC EDITOR: Please respond to all reviewer comments1. Clarify the type of study in title to avoid confusion as it is a follow up analysis of a RCT

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

Please submit your revised manuscript by Mar 15 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Ahmed Mohamed Maged, MD

Academic Editor

PLOS ONE

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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?

Reviewer #1: Yes

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

Reviewer #1: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

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

Reviewer #1: Yes

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Reviewer #1: Thank you for the opportunity to read this well conducted and interesting article. Broadly, I think this is a strong article, but more methodological detail is needed. I should note that as a health economist focused on conducting economic evaluations in the UK, I am not familiar with the associated Dutch guidelines – please consider that in relation to my feedback.

I structure my feedback with starting with what I consider the most important points, leading to more minor ones..

Methodological points:

• I feel strongly that the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) checklist should be completed and followed: https://www.equator-network.org/reporting-guidelines/cheers/

• More detail is needed around missing data: for example, how many imputations were used in the multiple imputation? What were the patterns of missing data? Please review Faria et al 2014 and follow its suggestions: https://pubmed.ncbi.nlm.nih.gov/25069632/

At minimum, I would like to see some plots of missing data in supplementary materials.

• How did you combine bootstrapping with the multiple imputation? Did you bootstrap from each imputed data-set?

• Regression models: did you control for any other variables? Was there any stratification in randomisation of the RCT? If there was, these variables should be included in your regression models. Did you adjust for site? Generally speaking, I would try to follow the statistical approach adopted in the RCT as far as possible – they may used a mixed effects model, which may preclude a SUR model.

• L122-124 – what valuation set was used to turn EQ-5D scores into utilities?

• Was discounting used for the second year of costs and effects? (May depend on the Dutch guidelines)

Supplementary tables with finer detail of resource and cost break down is needed – more detail is needed than just table 4 – perhaps one table, with a row for each “unit cost” resource, comparing arms. Should be repeated for costs.

Precision: Table 4 and more generally: I am very unconvinced that clarity is provided by including cents – why not round costs to the nearest euro? Could you use a thousands separator?

Figures 1-4: I am unconvinced you need both the CE planes and CEACs – why not move the CE-planes to supplementary materials? Also, I think it is a waste of space to have separate figures for the CEACs – why not one plot, with two lines?

L213: “the procedures showed equal effectiveness expressed in QALYs” – I would advise caution with this statement – I think some statisticians would argue that you have not done a non-inferiority study on comparing procedures, so can’t claim equal effectiveness – rather, you have found no statistically significant evidence of difference – the arguments are not reversible. I tend to follow Claxton 1999 (https://doi.org/10.1016/s0167-6296(98)00039-3) on this point, and would focus on the point estimates and the certainty of findings.

More minor points:

L21, Abstract: “Common condition”– include some numbers to speak to this?

L23, Abstract: “As the costs in healthcare are rising, the question raises whether an economic evaluation likewise points out in the direction of the Manchester procedure.” – I found this hard to parse – perhaps something like: “It is also important to consider the resource and associated cost implications of the choice between these two procedures – we conduct an economic evaluation to compare the alternative costs and benefits.”

L61/62: I’m unconvinced the main point is that healthcare costs are rising (not that I disagree) – I would just make the point you want to do the best with available resources – as argued in L63 – perhaps particularly relevant if the healthcare system is publicly funded.

L69: First mention of “SAM study” - should be spelt out/introduced.

Table 1: I find the “units” column unhelpful – I would suggest absorbing the related detail in the resource label, or the unit price – e.g. for the latter, in terms of travel costs – “0.19/km” etc

Table 1: The unit costs introduce the idea of “re-intervention” and complications – these should be motivated/covered when the procedures are introduced/perhaps in the background. For example, if randomised to the Manchester procedure and a re-intervention is necessary, which of the Manchester procedure or Sacrospinous would be used?

Table 5: It would seem natural to extend the table with QALYs at 1 year, 2 years and in total.

L192, L196: To convey some of the uncertainty etc, would it be useful to report the percentage of points falling in the South-East (more-effective, less costly) quadrant of the CE plane?

L218-233: You assert that the important costs and consequences are captured in two years, though others have used models, which I assume have a longer time horizon than 2 years – please add a sentence or two to address this – what was the time horizon in these models? Why didn’t they stop at two years? Etc More broadly, in your literature overview, I think it would be useful to capture the time horizon of these models – is there any “correlation”/link between the time horizon and positive/negative CE findings?

Very minor points:

L65: Perhaps replace: “likewise points out in the direction of” -> “similarly favours”

L75: Replace “in case” with “if”?

L103: eCRF needs spelling at first use.

L109: I think pluralise “unit cost” – more than one unit?

Table 1: TVT needs spelling out

L121: I believe more standard for EQ5D to be capitalised as “EQ-5D-5L”, as per the EuroQol website: https://euroqol.org/information-and-support/euroqol-instruments/eq-5d-5l/

L139: It seems odd to me that data extraction from CastorEDC are mentioned here – why not move this sentence to L102-108 etc?

Table 2: You include variables that are not baseline characteristics (e.g. primary outcome and reintervention etc) – please update the caption. Would some of these variables sit better in Table 3?

L200: Should “if” be “as”?

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Reviewer #1: No

**********

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PONE-D-24-40477R1

Economic evaluation of Manchester procedure versus sacrospinous hysteropexy: secondary outcome analysis of a randomized clinical trial

PLOS ONE

Dear Dr. Schulten,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we have decided that your manuscript does not meet our criteria for publication and must therefore be rejected.

Specifically:

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

ACADEMIC EDITOR:

The authors failed to respond to all reviewers and editors comments

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

I am sorry that we cannot be more positive on this occasion, but hope that you appreciate the reasons for this decision.

Kind regards,

Ahmed Mohamed Maged, MD

Academic Editor

PLOS ONE

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- - - - -

For journal use only: PONEDEC3

Dear Dr. Schulten,

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 Aug 20 2025 11:59 PM. 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.<wbr />com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• 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 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,

Ozan Karadeniz

Academic Editor

PLOS ONE

Journal Requirements:

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. 

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 (if provided):

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.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Partly

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #2: Positives :

The title adequately describes the study

The Economic evaluation of Manchester procedure versus sacrospinous hysteropexy" is a comprehensive assessment comparing the alternative costs and benefits of different healthcare procedures

The CHEERS 2022 checklist was followed

Methods used to asses direct costs , indirect costs and QALYs are all standard

Conclusions reached are representative barring a few concerns

Negatives

The 2-year follow-up is too short to reflect long term societal costs based on the definition of failure in this paper [mass symptoms which requires pessary/ surgical intervention]. As all mass symptoms do not require surgery and the progressive nature of prolapse which can worsen over time

Longer follow up of atleast 5 years is often needed to capture ongoing treatment costs, disease progression, and long-term economic consequences as stated in the conclusion

Kindly explain how all relevant cost and effect differences were calculated if [Line 96-97] there is no reliable data available regarding the number of women who undergo specific procedures as a second intervention how can costs be calculated

To conclude [ line 233-34]that the recurrence rates are lower than other comparative studies 2yr vs 5 year follow up is erroneous.

Reviewer #3: The present issue places the consequence of the SAM study, which concluded that sacrospinous hysteropexy is inferior to the Manchester procedure.

Through the present articles, sacrospinous hysteropexy is not entirely inferior to Manchester procedure, taking into consideration about the QALYs.

Actually, almost half of participants belong to the POP-Q 2nd degree. Strictly speaking, those patients tend to be cured even by the use of Pessary, the cheapest procedure. However, this time the highlight is the comparison between sacrospinous hysteropexy and Manchester procedure and not focused on the other procedures.

So far as this second revised articles, there are no suspicious points for me. I really respect your hard works.

**********

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.

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Reviewer #2: Yes:  Lilly Varghese

Reviewer #3: No

**********

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Dear Dr. Schulten;

publication criteria  and not, for example, on novelty or perceived impact.

Please submit your revised manuscript by Oct 31 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.

• 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 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,

Ozan Karadeniz

Academic Editor

PLOS ONE

Journal Requirements:

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. 

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.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

Reviewer #4: Yes

**********

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

Reviewer #2: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

Reviewer #4: Yes

**********

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

Reviewer #2: Yes

Reviewer #4: Yes

**********

Reviewer #2: No further comments. All points were clarified and minor corrections made.

I wish the authors all the very best in their work

Reviewer #4: 1. Overall, the study is well-written and flows smoothly. The findings and the authors’ intentions are clear and easy to follow. I appreciate the hard work involved and am impressed by the initial effort that went into designing and completing the SAM study. Based on its results, it is evident that the Manchester procedure is more cost-effective, primarily due to its lower recurrence rate. This naturally may make the readers wonder what the composition of reoperations is, but it is not critical. While the actual costs may not precisely reflect those in other countries (particularly the U.S.), the analysis provides useful context for cost considerations in that setting.

2. The authors have also adequately revised the manuscript in response to the reviewers’ previous comments; however, I have added a few more that need answering.

3. Great spin-off of the initial RCT.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #2: Yes:  Lilly Varghese

Reviewer #4: Yes:  Youngwu Kim

**********

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Attachments

Attachment

Submitted filename: review_PLOS_sslf_2025.docx

Economic evaluation of Manchester procedure versus sacrospinous hysteropexy: a follow-up analysis of a randomized clinical trial

PONE-D-24-40477R4

Dear Dr. Schulten,

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,

Ozan Karadeniz

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors are to be commended for conducting a well-designed randomized clinical trial comparing the Manchester procedure and sacrospinous hysteropexy and for providing an important economic evaluation with extended follow-up data. The analyses are clearly presented, and the discussion appropriately contextualizes the findings within the existing literature.

Minor technical issues remain and will be addressed during the final production process. Once these are completed, the manuscript will be ready for publication. The study contributes valuable evidence to guide surgical decision-making in the management of uterine prolapse, especially regarding cost-effectiveness and long-term outcomes.

I would like to sincerely thank all reviewers for their thoughtful and constructive evaluations of this manuscript. Your detailed comments and valuable insights have greatly contributed to improving the scientific quality and clarity of the paper. We truly appreciate the time and expertise you have dedicated to this review process.