Economic burden and cost-effectiveness of treatments for open tibia fractures in Malawi: Economic analysis of a multicentre prospective cohort study

Alexander Thomas Schade; Linda Alinafe Sande; Ewan Tomeny; Maureen Sabawo; Nyamulani Nohakhelha; Kaweme Mwafulirwa; Leonard Banza Ngoie; Andrew John Metcalfe; David Griffith Lalloo; William James Harrison; Jason J. Madan; Peter MacPherson

doi:10.1371/journal.pone.0331569

Peer Review History

Original SubmissionSeptember 16, 2024
4 Apr 2025 Decision Letter - Xiaoen Wei, Editor Dear Dr. Schade, 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 study suggests that intramedullary nailing is the most cost-effective treatment for open tibia fractures in Malawi. However, the practical implementation of this finding might require further discussion: - Training of orthopedic surgeons: Given the shortage of trained orthopedic surgeons in Malawi, the feasibility of expanding surgical treatments should be addressed. If intramedullary nailing is to be widely adopted, investment in surgeon training and infrastructure is necessary. - Accessibility of surgical care: Since most fractures in Malawi are treated non-operatively by Clinical Officers, the study should discuss whether a shift toward surgical management is realistically achievable within the current healthcare system. These aspects would strengthen the clinical relevance of the study and help translate findings into practical recommendations. Please submit your revised manuscript by May 19 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, Xiaoen Wei 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 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. Please include a complete copy of PLOS’ questionnaire on inclusivity in global research in your revised manuscript. Our policy for research in this area aims to improve transparency in the reporting of research performed outside of researchers’ own country or community. 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At this time, please upload the minimal data set necessary to replicate your study's findings to a stable, public repository (such as figshare or Dryad) and provide us with the relevant URLs, DOIs, or accession numbers that may be used to access these data. For a list of recommended repositories and additional information on PLOS standards for data deposition, please see https://journals.plos.org/plosone/s/recommended-repositories . 6. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author, or email us at plosone@plos.org with a request to remove this option. 7. 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: The study suggests that intramedullary nailing is the most cost-effective treatment for open tibia fractures in Malawi. However, the practical implementation of this finding might require further discussion: Given the shortage of trained orthopedic surgeons in Malawi, the feasibility of expanding surgical treatments should be addressed. If intramedullary nailing is to be widely adopted, investment in surgeon training and infrastructure is necessary. Since most fractures in Malawi are treated non-operatively by Clinical Officers, the study should discuss whether a shift toward surgical management is realistically achievable within the current healthcare system. These aspects would strengthen the clinical relevance of the study and help translate findings into practical recommendations. [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? Reviewer #1: Yes ******** 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 ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes ****** Reviewer #1: The study suggests that intramedullary nailing is the most cost-effective treatment for open tibia fractures in Malawi. However, the practical implementation of this finding might require further discussion: - Training of orthopedic surgeons: Given the shortage of trained orthopedic surgeons in Malawi, the feasibility of expanding surgical treatments should be addressed. If intramedullary nailing is to be widely adopted, investment in surgeon training and infrastructure is necessary. - Accessibility of surgical care: Since most fractures in Malawi are treated non-operatively by Clinical Officers, the study should discuss whether a shift toward surgical management is realistically achievable within the current healthcare system. These aspects would strengthen the clinical relevance of the study and help translate findings into practical recommendations. ****** 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: Gianmarco Vavalle ******** [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 https://doi.org/10.1371/journal.pone.0331569.r001
Revision 1
31 May 2025 Author Response I write on behalf of my co-authors to thank the reviewers for their careful review and appreciate the opportunity to respond with a revised submission. The authors have declared that no competing interests exist. Please see the point-by-point responses below. Attachments Attachment Submitted filename: PLOS_one_revisions_4.4.25.docx https://doi.org/10.1371/journal.pone.0331569.r002
21 Jun 2025 Decision Letter - Xiaoen Wei, Editor Dear Dr. Schade, Please submit your revised manuscript by Aug 05 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 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, Xiaoen Wei Academic Editor PLOS ONE [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: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes Reviewer #3: Partly ****** 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: (No Response) ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #2: While I give kudos to the authors, I think the discussion could be more robust judging by data analysis provided. So, I suggest the author beef up the discussion section with relevant citations. This will justify the data analysis provided. Reviewer #3: Abstract - Open tibia fracture can have an equal impact on women, what makes it more detrimental to men according to your research? - We obtained quality adjusted life years (QALYs) from the EuroQoL 5 Dimension 3 Level (EQ-5D-3L)… - Why were costs reported in 2021; at least inflate to 2024, or better still, report using 2024 costs. Background Method - The study protocol was published -------include date it was published. Ln 99 - Write the statement to make meaning or remove the bracket and let it be a complete sentence: At recruitment …. study. Lns 133-135 - Each procedure was observed between 1-3 times. - What was observed? Ln 154 - Did the difference in the way the costs were collected impact the study? - How was missing data inputted? Result - What was the incremental change in Costs and QALYs. Can the QALY per treatment type and location (central vs district) be included? What is the difference between costs and QALYs based on where the treatment took place? - Can you include a table showing the costs, QALYs, Incremental Costs, Incremental QALYs and ICER values - ****** 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 #2: Yes: Anthony Olasinde Reviewer #3: 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.] 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. Attachments Attachment Submitted filename: review for PlosOne.docx https://doi.org/10.1371/journal.pone.0331569.r003
Revision 2
17 Jul 2025 Author Response 1. Reviewer 2 Comment #1: Reviewer #2: While I give kudos to the authors, I think the discussion could be more robust judging by data analysis provided. So, I suggest the author beef up the discussion section with relevant citations. This will justify the data analysis provided. Author’s Response: We thank the reviewer for their positive feedback and constructive suggestion. In response, we have substantially revised and expanded the Discussion section to better contextualise our findings and strengthen the link between the data analysis and its implications. Specifically, we have incorporated additional references to relevant literature (1-4), including recent studies in similar settings, to support our interpretations and highlight the significance of our results. Lines: 275 “Orthopaedic interventions might not be affordable to the Malawi government, but substantial investment in trauma care will be required from government and stakeholders to reduce the large societal impact of injury (1)” Line 296 Open tibia fractures have devastating economic consequences on patients and their households too (2). Line 313 Further research should focus on factors and outcomes that improve the return of income such as social support and rehabilitation on injury (3). Line 315 As LMIC economies grow and motor transport becomes more common, fractures are placing a large financial strain on the economies (4). ” Reviewer #3: Comment #1: Open tibia fracture can have an equal impact on women, what makes it more detrimental to men according to your research? Author’s Response: Thank you for your comment. Open tibia fractures can indeed have a significant impact on both men and women. However, in our cohort, 84% of patients were male, which is consistent with global data showing that traumatic injuries disproportionately affect young men (4). In the Malawian context, cultural norms often position men as the primary income earners (5). As a result, the economic consequences of injury may be more pronounced for men, particularly in terms of lost income and reduced household stability. To our knowledge, this socioeconomic impact has not been previously documented in this setting and warrants further investigation. Comment #2: We obtained quality adjusted life years (QALYs) from the EuroQoL 5 Dimension 3 Level (EQ-5D-3L)… Author’s Response: Many thanks, we have amended the abstract accordingly. Comment #2: Why were costs reported in 2021; at least inflate to 2024, or better still, report using 2024 costs. Author’s Response: Thank you for your comment. As outlined in the methods section, recruitment took place between 12 February 2021 and 15 March 2022. To reflect the timing of data collection and ensure consistency, costs were reported in 2021 values. Comment #3: The study protocol was published -------include date it was published. Ln 99 Author’s Response: Thank you for highlighting this. The study protocol was published in 2021, and we have now included the publication year at line 99 in the Methods section for clarity. Lines: 100 “The study protocol was previously published in 2021” Comment #3: Write the statement to make meaning or remove the bracket and let it be a complete sentence: At recruitment …. study. Lns 133-135 Author’s Response: Thank you for your suggestion. We have revised and completed the sentence for clarity. Line 134 “At recruitment, participants were asked to retrospectively complete the questionnaire for their health state pre-injury and at each subsequent follow-up visit, study.” Comment #3: Each procedure was observed between 1-3 times. - What was observed? Ln 154 Author’s Response: Thank you for highlighting this point. We have revised the manuscript to clarify what aspects of the procedure were observed. Specifically, we have added a description of the patient treatment pathway in the main text and detailed which procedures were directly observed in Appendix A. This should make the scope and focus of the observations clearer to the reader. Comment #3: - Did the difference in the way the costs were collected impact the study? Author’s Response: Thank you for your comment. Due to the lower frequency of open tibia fractures in district hospitals, we were unable to conduct time-and-motion analyses at those sites. This difference in data collection methods may have introduced some limitations, which we have now acknowledged and discussed in the limitations section of the manuscript. Comment #4 - How was missing data inputted? Thank you for your question. Observations with missing data were excluded from the relevant analyses. Given the small number of missing values, we did not attempt formal imputation. Where appropriate, we conducted sensitivity analyses to assess the potential impact of missing data on our findings. Comment #5 - What was the incremental change in Costs and QALYs. Can the QALY per treatment type and location (central vs district) be included? What is the difference between costs and QALYs based on where the treatment took place? - Can you include a table showing the costs, QALYs, Incremental Costs, Incremental QALYs and ICER values Thank you for your helpful comments. As clarified in the revised manuscript, Table 2 presents the total costs, incremental costs, and cost per QALY (ICER) for each treatment type, stratified by treatment location (central vs district hospitals). This allows for direct comparison of cost-effectiveness across settings. QALYs and incremental QALYs were reported in our previous publication (7) and are not reproduced in full here to avoid duplication. However, the ICER values in Table 2 incorporate these published QALY estimates to provide a comprehensive assessment of cost-utility. Attachments Attachment Submitted filename: PLOSONE_responses.docx https://doi.org/10.1371/journal.pone.0331569.r004
19 Aug 2025 Decision Letter - Xiaoen Wei, Editor Economic burden and cost-effectiveness of treatments for open tibia fractures in Malawi: economic analysis of a multicentre prospective cohort study PONE-D-24-40054R2 Dear Dr. Schade, 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, Xiaoen Wei Academic Editor PLOS ONE Additional Editor Comments (optional): 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes ****** Reviewer #2: I have no further coment to make. The authors have addressed the previously ones. THE Editorial should make the final decision on the manuscript ****** 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 #2: Yes: Anthony Olasinde ******** https://doi.org/10.1371/journal.pone.0331569.r005
Formally Accepted
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