Endobronchial ultrasound-guided transbronchial needle aspiration versus mediastinoscopy for mediastinal staging of lung cancer: A systematic review of economic evaluation studies

João Pedro Steinhauser Motta; Ricardo E. Steffen; Caroliny Samary Lobato; Vanessa Souza Mendonça; José Roberto Lapa e Silva

doi:10.1371/journal.pone.0235479

Peer Review History

Original SubmissionJanuary 16, 2020
13 Mar 2020 Decision Letter - Jules Lin, Editor PONE-D-20-00791 ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION VERSUS MEDIASTINOSCOPY FOR MEDIASTINAL STAGING OF LUNG CANCER: SYSTEMATIC REVIEW OF ECONOMIC EVALUATION STUDIES PLOS ONE Dear Dr Steinhauser Motta, Thank you for submitting your manuscript to PLOS ONE. In this study, Mota, et al. performed a systematic review of 8 studies evaluating the cost effectiveness of EBUS compared to mediastinoscopy in lung cancer. The study is of interest to readers. Several questions and comments were raised by the reviewers. Please consider these suggestions thoughtfully as they are meant to be constructive. 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 authors should consider including a funnel plot to their results. The cost-effectiveness and cost-savings data should be combined in a separate table. While the authors demonstrate that EBUS is cost-effective compared to mediastinoscopy, the potential limitations of EBUS should be included in the discussion. EBUS is operator dependent and full mediastinal staging with systematic sampling of multiple lymph node stations should be encouraged rather than FNA of a single lymph node. Training and quality control with rapid on-site evaluation (ROSE) are also important for those early in their experience with EBUS. There also continues to be a role for mediastinoscopy in cases where EBUS is non-diagnostic or there remains a high suspicion of positive mediastinal disease despite a negative EBUS. Please have the paper reviewed by a native English speaker. There are several typographical and grammatical errors in the manuscript as pointed out by the reviewers. We would appreciate receiving your revised manuscript by Apr 27 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. 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The PLOS ONE style templates can be found at http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf [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? 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 #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No 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: No 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: I would like to thank the authors for allowing us to read their manuscript. This systematic review article evaluates and compares the cost /effectiveness of both EBUS vs mediastinoscopy in patients with lung cancer. The authors have selected an important and difficult area for study. The main goal of this paper is to evaluate the economic impact of EBUS and compared to mediastinoscopy. I do not find problems with this study ethics. Funding is clearly stated. Manuscript Strengths: - Abstract: Well presented, see minor comments - Introduction: Overall, well presented. See comments - Material and methods. I find it focused, with all inclusion/exclusion criteria and informative. There was a comprehensive literature search, the information sources were listed. Not redundant. See comments for suggestions. In regard to the data abstraction, it seems there was not structured data abstraction form used, however, there is description of the number of authors who abstracted the data, how they resolved disagreements, and some characteristics of all the studies used (See comments). - Results: Needs to be re-organized for the reader to follow. See comments - Discussion. The discussion is as well-balanced with mention made of some obvious limitations associated with the heterogeneity’s of the studies. - Conclusions: Well written, clear. I would like to raise the following major points: - In the introduction section: o Please consider including a clinically relevant and focused main study question. The objective is stated, but what is the authors main question to solve? This needs to be explicitly stated and will need to describe primary and secondary objectives. o Please consider adding if the cost /effectiveness of EBUS vs mediastinoscopy has NOT been clearly demonstrated in prior clinical trials. - In the material and methods: o Please explain if a funnel plot was used o Please consider adding � If the author had made attempts at collecting unpublished data � If a structured data abstraction form was used when selecting/scoring the studies � The size (n) of population for each study in Table 1. - Results. o There was repetition in the sub-section outcomes. results and sensitivity analysis’ paragraphs and Table 3. Please consider highlighting most relevant data. Tables and figures both need minor changes. See comments for suggestions. o Could the authors consider cost-effectiveness and cost-savings description of data be be condensed on a separate table? And just include one or two shorter paragraphs to add some additional data/guide the reader? - The discussion is very well written and succinct. It describes the major findings and acknowledges the limitations of this meta-analysis. o There is an obvious trend of EBUS to be more cost effective when compared to mediastinoscopy. My major concern was that the cost items in all eight studies are very heterogenous. The authors elegantly describe how they reconciled this fact. I would like, however ask the authors if were all these eight studies, in their opinion, combinable? If so, please add this in the discussion. I noticed that a funnel plot was not used. Was this necessary, if not, was the sensitivity analysis enough? Please explain. o Please consider mentioning that additionally, EUS will not be able to sample hilar lymph nodes but mediastinal). Minor comments: - Abstract. Correct misspelling “statement”. Consider changing keys for keywords, pulmonary neoplasia for lung cancer or thoracic malignancy. - Line 153, misspelling “Computer” for “Computed”. Should read Chest computed tomography - Line 180, please spell out DRG abbreviation - Line 209, Please clarify if the authors meant EUS or EBUS or both. - Line 269. Maybe a typo. I only found 8 articles used, but it is written “nine” - Line 334. Delete “the” - Table 1. o Please correct the word “cost-effectiveness”, “available”, “months” - Consider changing “thorax CT” for “Chest CT” throughout the document - Table 3. Add in authors column the corresponding # of bibliography. Consider capital letter in sensitivity analysis column. Multiple misspellings: “n.a.” and “available”, computer for “computed”. Summary: In particular, this systematic review confirmed the cost effectiveness of EBUS when compared to mediastinoscopy on patients with thoracic malignancy. Clear limitations of the analysis are stated. I do think that the journal readers, will find this paper - once reviewed- helpful and thought-provoking for future health-economic research. Reviewer #2: The authors conducted a systematic review of the economic evaluation of EBUS vs mediastinoscopy in a contemporary time period. They ultimately included 8 studies in the review and overall this shows that EBUS is a cost-effective procedure for lung cancer staging compared to mediastinoscopy. This is a relevant and interesting topic, as some places in the world do not have full access to this technology. I have a few comments for the authors to help strengthen the manuscript. 1. Abstract intro: EBUS did not change the approach of pulmonary neoplasia. It has changed the approach to staging pulmonary neoplasia. This should be corrected throughout the manuscript. 2. There are several typos throughout the manuscript that need to be corrected prior to publication. 3. I assume the column heading in Table 1 should read "Sensitivity Analysis" and not Sensitive 4. The discussion would be strengthened by mention of the potential limitations of EBUS, in that it is highly operator dependent, ie the time spent doing the procedure by an experienced operator systematically sampling all nodal stations will likely have significantly different outcomes in terms of nodal sampling rate, etc than one done by an inexperienced operator only sampling one node. While this is not directly related to the findings from the included studies, it could impact cost ultimately. Given that most older experienced thoracic surgeons are more familiar with mediastinoscopy than EBUS, I think the inclusion of some discussion about the importance of adequate training and quality control of EBUS, including Rapid On-site Evaluation (ROSE) of specimens should be included, even if not mentioned in the included studies. Overall, I think the manuscript is well put together and I congratulate the authors on their work. ****** 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: No 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0235479.r001
Revision 1
10 Apr 2020 Author Response Dear academic editor and reviewers, Thank you very much for taking the time to review the article “Endobronchial ultrasound-guided transbronchial needle aspiration versus mediastinoscopy for mediastinal staging of lung cancer: systematic review of economic evaluation studies” submitted to Plos One. I am sure that the comments and suggestions made will improve the scientific quality of the article and interest for future readers. 1. Responses to the points raised by the academic editor: • The authors should consider including a funnel plot to their results – the following paragraph was added to the manuscript on lines 311-321: “Risk of bias across studies is particularly relevant when a systematic review combines evidence on treatment effects across multiple studies. However, our review seeks to evaluate the results, methodological and reporting quality of economic evaluation studies, rather than the effect of any particular intervention, and did not combine results across studies. Tools for assessing publication or selective reporting bias (i.e. funnel plots) have been designed for examining treatment effect of interventions, which cannot be applied to our study. We minimized publication bias by searching available protocols for economic evaluation studies of EBUS versus mediastinoscopy in systematic review registries available (ie. Prospero database). Additional assessment of the risk of bias across studies was also based on evaluations of each study’s funding source and the nature of disclosed conflict of interest for each study.” • The cost-effectiveness and cost-savings data should be combined in a separate table – Table 3 was divided into 2 tables (table 3 and table 4). Table 3 presents the interventions, comparators and outcomes of each study and Table 4 shows the results of cost-effectiveness, cost reduction and sensitivity analysis. Changes were made to the text of the manuscript with the inclusion of a sub-section with the title “Intervention, comparators and outcomes” and another with the title “Cost-effectiveness, cost-savings and sensitivity analysis results. The main information in the tables is described in these 2 subsections. • While the authors demonstrate that EBUS is cost-effective compared to mediastinoscopy, the potential limitations of EBUS should be included in the discussion – the potential limitation of EBUS were included in the discussion as follows on line 342 to 354: “Finally, although not addressed in the studies evaluated by this systematic review, it is important to note that the EBUS technique is highly operator dependent and the results of a service with little experience can differ greatly from those published in the literature by experts. A complete mediastinal staging approach with systematic sampling of all multiple lymph node stations is quite different and more difficult to do than just sampling one suspected lymph node. Ensuring adequate training and quality control of the results obtained by EBUS is essential for the establishment of reference centers in the technique (34). In this context, although evidence is insufficient to recommend that rapid onset evaluation (ROSE) should be used in every procedure (35), the presence of the pathologist in the bronchoscopy room can be of great value in guiding less experienced operators in obtaining representative lymph node samples. In cases where the clinical suspicion of mediastinal node involvement remains high after a negative result using a needle technique, surgical staging with mediastinoscopy should be considered (3).” • Please have the paper reviewed by a native English speaker. There are several typographical and grammatical errors in the manuscript as pointed out by the reviewers – the manuscript was reviewed by a native English speaker and the typographical and grammatical errors were corrected. 2. Responses to the points raised by Reviewer 1: • In regard to the data abstraction, it seems there was not structured data abstraction form used - A structured data abstraction form was used and the form can now be accessed in the supporting information session. This information is now written in the manuscript as follows on lines 113-14: “A structured data abstraction form was used and can also be accessed in the supporting information session of this article.” • Please consider including a clinically relevant and focused main study question. The objective is stated, but what is the authors main question to solve? This needs to be explicitly stated and will need to describe primary and secondary objectives – The main study question and description of primary and secondary objectives were included as follows on lines 69 – 71 “An important question to be answered at this point is: is the use of EBUS for the mediastinal staging of lung cancer cost-effective when compared to mediastinoscopy?”and 73 – 80 “The primary objective of this study is to understand the cost-effectiveness ratio of EBUS compared to mediastinoscopy for invasive mediastinal staging of lung cancer. Secondary objectives are to identify the most relevant economic evaluation studies published comparing EBUS to mediastinoscopy and what types of models were used in those evaluations, to understand the most important economic trade-offs and to guide future economic assessments to be carried out in countries with different health systems.” • Please consider adding if the cost /effectiveness of EBUS vs mediastinoscopy has NOT been clearly demonstrated in prior clinical trials – This information was added to the manuscript on lines 73-74: “but until now the cost-effectiveness of EBUS versus mediastinoscopy has not been clearly demonstrated in prior clinical trials.” • Please explain if a funnel plot was used - the following paragraph was added to the manuscript on lines 311-321: “Risk of bias across studies is particularly relevant when a systematic review combines evidence on treatment effects across multiple studies. However, our review seeks to evaluate the results, methodological and reporting quality of economic evaluation studies, rather than the effect of any particular intervention, and did not combine results across studies. Tools for assessing publication or selective reporting bias (i.e. funnel plots) have been designed for examining treatment effect of interventions, which cannot be applied to our study. We minimized publication bias by searching available protocols for economic evaluation studies of EBUS versus mediastinoscopy in systematic review registries available (ie. Prospero database). Additional assessment of the risk of bias across studies was also based on evaluations of each study’s funding source and the nature of disclosed conflict of interest for each study.” • Please consider adding if the author had made attempts at collecting unpublished data – This information was added to the manuscript on lines 99-100 as follows: “The authors chose not to include unpublished data and gray literature in the searches.” • Please consider adding if a structured data abstraction form was used when selecting/scoring the studies - A structured data abstraction form was used and the form can now be accessed in the supporting information session. This information is now written in the manuscript as follows on lines 113-14: “A structured data abstraction form was used and can also be accessed in the supporting information session of this article.” • Please consider adding the size (n) of population for each study in Table 1 – The size (N) of population for each study was added in Table 1. • There was repetition in the sub-section outcomes. results and sensitivity analysis’ paragraphs and Table 3. Please consider highlighting most relevant data – The authors agreed that there was an excess of repeated information between the sub-section outcomes, results and sensitivity analysis of the manuscript and table 3. Table 3 was divided in 2 Tables (Table 3 and Table 4) and the sub-section “Outcomes, results and sensitivity analysis” was divided in 2 sub-sections: “Intervention, comparators and outcomes” and “Cost-effectiveness, cost-savings and sensitivity analysis results”. The more detailed information was taken from the text and only the messages that we consider most important from each article were left to be highlighted. • Could the authors consider cost-effectiveness and cost-savings description of data be condensed on a separate table? And just include one or two shorter paragraphs to add some additional data/guide the reader? – Table 3 was divided into 2 tables (table 3 and table 4). Table 3 presents the interventions, comparators and outcomes of each study and Table 4 shows the results of cost-effectiveness, cost-savings and sensitivity analysis. Changes were made to the text of the manuscript with the inclusion of a sub-section with the title “Intervention, comparators and outcomes” and another with the title “Cost-effectiveness, cost-savings and sensitivity analysis results”. The main information in the tables is described in these 2 subsections. • I would like, however ask the authors if were all these eight studies, in their opinion, combinable? If so, please add this in the discussion. I noticed that a funnel plot was not used. Was this necessary, if not, was the sensitivity analysis enough? Please explain - the following paragraph was added to the manuscript on lines 311-321: “Risk of bias across studies is particularly relevant when a systematic review combines evidence on treatment effects across multiple studies. However, our review seeks to evaluate the results, methodological and reporting quality of economic evaluation studies, rather than the effect of any particular intervention, and did not combine results across studies. Tools for assessing publication or selective reporting bias (i.e. funnel plots) have been designed for examining treatment effect of interventions, which cannot be applied to our study. We minimized publication bias by searching available protocols for economic evaluation studies of EBUS versus mediastinoscopy in systematic review registries available (ie. Prospero database). Additional assessment of the risk of bias across studies was also based on evaluations of each study’s funding source and the nature of disclosed conflict of interest for each study.” • Please consider mentioning that additionally, EUS will not be able to sample hilar lymph nodes but mediastinal – This information was added to the manuscript on lines 337 – 340 as follows: “It is also important to note that the use of EUS has the limitation of not evaluating hilar lymph nodes, which may be important for defining the most appropriate therapeutic strategy in some cases.” • Minor comments: • Abstract. Correct misspelling “statement”. Consider changing keys for keywords, pulmonary neoplasia for lung cancer or thoracic malignancy – Correction and changes were made on lines 26 – 27 “The emergence of endobronchial ultrasound (EBUS) changed the approach to staging lung cancer” and 31 – 32 “…according to the PRISMA statement and registred on PROSPERO (CRD42019107901). Search keywords were elaborated considering descriptors…” of the manuscript. • Line 153, misspelling “Computer” for “Computed”. Should read Chest computed tomography – Correction was made as follows now on lines 168-169: “…status based on chest computed tomography (CT) and positron emission tomography-computed tomography (PET-CT)…” • Line 180, please spell out DRG abbreviation – The abbreviation is now spelled as follows on line 194: “to national tariffs and/or Diagnosis Related Groups (DRG) fees (21, 23-25).” • Line 209, Please clarify if the authors meant EUS or EBUS or both – This sentence was removed from the text of the manuscript to leave only the most relevant information in the tables. Table 4 shows that: "EUS-FNA is the least expensive strategy for mediastinal lung cancer staging when N2 probability <32% / EUS + EBUS-TBNA is least expensive when N2 probability> 32%". • Line 269. Maybe a typo. I only found 8 articles used, but it is written “nine” – This is corrected on line 266 as follows: “The eight articles included in this review were…” • Line 334. Delete “the” – This is corrected on line 357 as follows: “…that EBUS-TBNA is cost effective compared to mediastinoscopy…” • Table 1 - Please correct the word “cost-effectiveness”, “available”, “months” – These corrections were made in Table 1. • Consider changing “thorax CT” for “Chest CT” throughout the document – This change was made throughout the document. • Table 3 Add in authors column the corresponding # of bibliography. Consider capital letter in sensitivity analysis column. Multiple misspellings: “n.a.” and “available”, computer for “computed” – These corrections and changes were made in Table 3. 3. Responses to the points raised by Reviewer 2: • Abstract intro: EBUS did not change the approach of pulmonary neoplasia. It has changed the approach to staging pulmonary neoplasia. This should be corrected throughout the manuscript – This correction was made throughout the manuscript as follows on line 26 “The emergence of endobronchial ultrasound (EBUS) changed the approach to staging lung cancer.” and 59 “...changed the approach to staging lung cancer...” • There are several typos throughout the manuscript that need to be corrected prior to publication – the manuscript was reviewed by a native English speaker and the typographical and grammatical errors were corrected. • I assume the column heading in Table 1 should read "Sensitivity Analysis" and not Sensitive – The column heading in Table 1 was corrected to “Sensitivity Analysis”. • The discussion would be strengthened by mention of the potential limitations of EBUS, in that it is highly operator dependent, ie the time spent doing the procedure by an experienced operator systematically sampling all nodal stations will likely have significantly different outcomes in terms of nodal sampling rate, etc than one done by an inexperienced operator only sampling one node. While this is not directly related to the findings from the included studies, it could impact cost ultimately. Given that most older experienced thoracic surgeons are more familiar with mediastinoscopy than EBUS, I think the inclusion of some discussion about the importance of adequate training and quality control of EBUS, including Rapid On-site Evaluation (ROSE) of specimens should be included, even if not mentioned in the included studies - the potential limitation of EBUS were included in the discussion as follows on line 342 to 354: “Finally, although not addressed in the studies evaluated by this systematic review, it is important to note that the EBUS technique is highly operator dependent and the results of a service with little experience can differ greatly from those published in the literature by experts. A complete mediastinal staging approach with systematic sampling of all multiple lymph node stations is quite different and more difficult to do than just sampling one suspected lymph node. Ensuring adequate training and quality control of the results obtained by EBUS is essential for the establishment of reference centers in the technique (34). In this context, although evidence is insufficient to recommend that rapid onset evaluation (ROSE) should be used in every procedure (35), the presence of the pathologist in the bronchoscopy room can be of great value in guiding less experienced operators in obtaining representative lymph node samples. In cases where the clinical suspicion of mediastinal node involvement remains high after a negative result using a needle technique, surgical staging with mediastinoscopy should be considered (3).” Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS .docx https://doi.org/10.1371/journal.pone.0235479.r002
17 Jun 2020 Decision Letter - Shawn Groth, Editor ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION VERSUS MEDIASTINOSCOPY FOR MEDIASTINAL STAGING OF LUNG CANCER: A SYSTEMATIC REVIEW OF ECONOMIC EVALUATION STUDIES PONE-D-20-00791R1 Dear Dr. Steinhauser Motta, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Shawn Groth Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have adequately responded to the critiques of the reviewers. 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 #1: All comments have been addressed 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 #1: Yes Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: (No Response) ****** 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 #1: Yes Reviewer #2: (No Response) ****** 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 #2: (No Response) ****** 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 #1: I do thank the authors for providing thoughtful and clear answers to each of my suggestions. I am satisfied with your replies. Reviewer #2: My comments and concerns from the review have been addressed. The manuscript is now stronger for these changes. ****** 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 https://doi.org/10.1371/journal.pone.0235479.r003
Formally Accepted
19 Jun 2020 Acceptance Letter - Shawn Groth, Editor PONE-D-20-00791R1 Endobronchial ultrasound-guided transbronchial needle aspiration versus mediastinoscopy for mediastinal staging of lung cancer: a systematic review of economic evaluation studies Dear Dr. Steinhauser Motta: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Shawn Groth Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0235479.r004

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