Economic evaluation of trastuzumab in HER2-positive early breast cancer in Indonesia: A cost-effectiveness analysis

Sudewi Mukaromah Khoirunnisa; Fithria Dyah Ayu Suryanegara; Didik Setiawan; Maarten Jacobus Postma; Lisa Aniek de Jong

doi:10.1371/journal.pone.0304483

Peer Review History

Original SubmissionOctober 20, 2023
2 Jan 2024 Decision Letter - Nabil Elhadi Elsayed Ali Omar, Editor PONE-D-23-33455Economic evaluation of trastuzumab in HER2-positive early breast cancer in Indonesia: a cost-effectiveness analysisPLOS ONE Dear Dr. khoirunnisa, 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 Feb 16 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. 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Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The manuscript is very interesting and well written, although I believe these comments could improve your manuscript. The abstract and introduction are interesting and well written. Materials and Methods Table 1 and Table 2; Hazard ratio overall survival, Hazard ratio Disease-free survival, and Hazard ratio for distant metastasis in table 1 from HERA trial, and table 2 from the joint analysis of NSABP B-31 and NCCTG177 N98313, why did you use table 1 inputs for base case with ICER 6,842 per QALY then use table 2 input for total population included in the joint analysis with ICER was US$5,292 per QALY, however you could use the table 2 inputs for both base case and Scenario analysis ( age subgroup), please clarify the value of using both data as it could be confusing for the reader. Note extracting HR for general population from a meta-analysis for the general population will give you more robust results instead of using 2 different RCT respecting to the recommendation of evidence ranking in health economics ( less confusing and more consistent), there are a meta-analysis 2021 covering this topic Line 195 “per-capita GDP” please add the value of per capita GDP in table 1 and illustrate per capita GDP for which year. Line 241 “For the total population included in the joint analysis, the ICER was US$5,292 per QALY.” It is not clear how this ICER was calculated (depends on which HR) Line 323 HERA trial you need to add the reference here. Line 158 “For estimating costs per health states, the proportion of resources used for each health states was utilized to finally calculate the total cost annually” as you depended on procedures costs from another country (India), it would be better to mention that in the limitation, as economic evaluations depend mainly on the costs in your country to be freely compare the ICER to your WTP threshold. Results are well interpreted , although it is recommended to improve the resolution of figure 2,3,4,5,6. The discussion is well written. Very important topic but you need to clarify a few points to be more reliable and reproducible Reviewer #2: Can you please provide a rational for extrapolating the transition probabilities and HRs from the mentioned clinical trials (follow up period 11 years) to 50 years in the Markov model? What suggests they will remain unchanged after 11 years? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Shaimaa Abdelaziz Abdelmoneim Reviewer #2: 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: PLOS ONE comments.pdf https://doi.org/10.1371/journal.pone.0304483.r001
Revision 1
15 Mar 2024 Author Response Reviewer 1 1. Materials and Methods Table 1 and Table 2; Hazard ratio overall survival, Hazard ratio Disease-free survival, and Hazard ratio for distant metastasis in table 1 from HERA trial, and table 2 from the joint analysis of NSABP B-31 and NCCTG177 N98313, why did you use table 1 inputs for base case with ICER 6,842 per QALY then use table 2 input for total population included in the joint analysis with ICER was US$5,292 per QALY, however you could use the table 2 inputs for both base case and Scenario analysis ( age subgroup), please clarify the value of using both data as it could be confusing for the reader. Note extracting HR for general population from a meta-analysis for the general population will give you more robust results instead of using 2 different RCT respecting to the recommendation of evidence ranking in health economics (less confusing and more consistent), there are a meta-analysis 2021 covering this topic Respond: The ICER for the base case was based on input parameters in the Table 1 (HERA trial), while in scenario analysis, the ICER for total population and age group in scenario analysis, was based on the joint analysis of NSABP B-31 and NCCTG177 N98313. The HERA trial was used in the base case analysis as this is the longest data available for the use of trastuzumab in breast cancer. We clarified about this in the the Materials and Methods, subsection Transition probabilities, Line 137-138. Thank you for your thoughtful suggestion regarding the extraction of hazard ratios (HR) for the general population from a meta-analysis. We acknowledge the importance of adhering to the recommended evidence ranking in health economics for a more robust and consistent approach. In response to your recommendation, we have explored a meta-analysis conducted in 2021 that provides a comprehensive analysis of the effectiveness and outcomes associated with trastuzumab treatment in breast cancer patients. However, the meta-analysis emphasized the analysis of the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality, which are not relevant to our model. 2. Line 195 “per-capita GDP” please add the value of per capita GDP in table 1 and illustrate per capita GDP for which year. Respond: Thank you for your comment. The value of per capita GDP was added in Table 1. 3. Line 241 “For the total population included in the joint analysis, the ICER was US$5,292 per QALY.” It is not clear how this ICER was calculated (depends on which HR) Respond: Thank you for your clarification. The explanation of the ICER calculation for the total population for scenario analysis was mentioned now in the Materials and Methods, subsection Scenario analysis, Lines 182-184. 4. Line 323 HERA trial you need to add the reference here. Respond: Thank you for your comment. The reference (Line 304) was added. 5. Line 158 “For estimating costs per health states, the proportion of resources used for each health states was utilized to finally calculate the total cost annually” as you depended on procedures costs from another country (India), it would be better to mention that in the limitation, as economic evaluations depend mainly on the costs in your country to be freely compare the ICER to your WTP threshold. Respond: Thank you for your comments. The procedure costs used in this study were derived from BPJS Kesehatan (mentioned in Materials and Methods, subsection Utilities and costs, Lines 149-154). However, due to the data constraints related to costs for each health states in Indonesia, we used the proportions of the patients receiving the treatments for each health states from India to finally calculate the health states costs. The limitation of the use was now mentioned in Discussion, Lines 353-355. 6. Results are well interpreted, although it is recommended to improve the resolution of figure 2,3,4,5,6. Respond: Thank you for your suggestions. We have improved the quality of the figures. 7. The discussion is well written. Very important topic but you need to clarify a few points to be more reliable and reproducible Respond: Thank you for your feedback. We greatly appreciate your positive assessment of the discussion section and acknowledge your valuable input regarding the need for clarification on certain points to enhance the reliability and reproducibility of our study. We have thoroughly reviewed your comments and have taken the necessary steps to address them in our manuscript. We believe that these revisions have significantly strengthened the reliability and reproducibility of our findings. Once again, thank you for your thoughtful feedback. We are confident that the improvements made will enhance the quality of our manuscript. Reviewer 2 Can you please provide a rational for extrapolating the transition probabilities and HRs from the mentioned clinical trials (follow up period 11 years) to 50 years in the Markov model? What suggests they will remain unchanged after 11 years? Respond: Thank you for your comments. While extrapolating data from an 11-year clinical trial to a 50-year timeframe involves assumptions and uncertainties, it might be a justifiable approach when considering the lack of long-term empirical evidence. However, acknowledging the limitations and uncertainties associated with this extrapolation is essential, and conducting sensitivity analyses and seeking expert input can enhance the credibility of these long-term predictions within the Markov model. In response to this comment, we conducted an additional sensitivity analysis covering this limitation, by simulating a treatment effect duration of trastuzumab of 11 years (equal to the follow-up of the trial) (Methods, subsection Scenario analysis, Lines 117-180). The ICER result based on the scenario analysis incorporating the efficacy of trastuzumab until 11 years showed that trastuzumab is cost-effective (Results, subsection Scenario analysis, Lines 223-225. We have now also added a paragraph in the discussion about this (Discussion, Lines 312-318) Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0304483.r002
14 May 2024 Decision Letter - Nabil Elhadi Elsayed Ali Omar, Editor Economic evaluation of trastuzumab in HER2-positive early breast cancer in Indonesia: a cost-effectiveness analysis PONE-D-23-33455R1 Dear Dr. khoirunnisa, 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. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. 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, Nabil Elhadi Elsayed Ali Omar, PharmD.,BCOP.,PhD(C) Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #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 requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: (No Response) ****** 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 #2: No ******** https://doi.org/10.1371/journal.pone.0304483.r003
Formally Accepted
16 May 2024 Acceptance Letter - Nabil Elhadi Elsayed Ali Omar, Editor PONE-D-23-33455R1 PLOS ONE Dear Dr. Khoirunnisa, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Nabil Elhadi Elsayed Ali Omar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0304483.r004

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