Comparison of FDA accelerated vs regular pathway approvals for lung cancer treatments between 2006 and 2018

Tatiane Bomfim Ribeiro; Lewis Buss; Cole Wayant; Moacyr Roberto Cuce Nobre

doi:10.1371/journal.pone.0236345

Peer Review History

Original SubmissionJanuary 9, 2020
21 May 2020 Decision Letter - Erika Cecchin, Editor PONE-D-20-00807 Comparison of FDA Accelerated vs Regular Pathway Approvals for Lung Cancer Treatments between 2006 and 2018 PLOS ONE Dear Dr. Bomfim Ribeiro, 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. Specifically some methodological issues were raised considering the statistical power of the studies discussed within the paper that should be addressed. Please submit your revised manuscript within 30 days. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Erika Cecchin Academic Editor PLOS ONE Journal requirements: When submitting your revision, we need you to address these additional requirements: 1. 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 http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: No ****** 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: Authors have compared FDA accelerated vs regular pathways approvals and breakthrough therapy designations for lung cancer treatment between 2006 and 2018. The authors concluded that fater approvals are in the majority full of uncertainties which should be viewed with caution and the patient have to be communicated to allow shared decision making. The manuscript is very well written and informative. It could be accepted for publication. Reviewer #2: Ribeiro and co. compared the approved accelerated and approved regular clinical studies. They stated that the “larger effect size” is not different from the accelerated one and the regular approval for FDA lung cancer approvals between 2006 and 2018. This suggestion is very important, but this statement should be better critically analysed. In particular the final conclusion could be biased, as also suggested by the authors, from the surrogated end points used in regular and accelerated approved studies. The Authors reported the GRADE method, but this method is based on the quality of evidences and substantial end point , i.e. the overall survival. Even if the Authors have evidenced several limitations of the analyses ( surrogate markers, lack of control group,…) they still conclude that there are not differences in the “larger effect size”. Specific comments • The effect size should be better explained and an explicative table, reporting statistics for all the parameter considered, could be useful • With regard to the study design, have the statistic power and the sample size been considered? ****** 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.] 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. https://doi.org/10.1371/journal.pone.0236345.r001
Revision 1
9 Jun 2020 Author Response Dear Editor, Dear Reviewers, Thank for your all useful comments on our manuscript. We have addressed them in the current version and we believe the manuscript has been improved. All changes made to the original version are highlighted in a marked up copy of our manuscript. Please find our responses below. Yours sincerely, Tatiane Ribeiro Reviewer #1: Authors have compared FDA accelerated vs regular pathways approvals and breakthrough therapy designations for lung cancer treatment between 2006 and 2018. The authors concluded that fater approvals are in the majority full of uncertainties which should be viewed with caution and the patient have to be communicated to allow shared decision making. The manuscript is very well written and informative. It could be accepted for publication. Thanks. Nothing to add. Reviewer #2: Ribeiro and co. compared the approved accelerated and approved regular clinical studies. They stated that the “larger effect size” is not different from the accelerated one and the regular approval for FDA lung cancer approvals between 2006 and 2018. This suggestion is very important, but this statement should be better critically analysed. In particular the final conclusion could be biased, as also suggested by the authors, from the surrogated end points used in regular and accelerated approved studies. The Authors reported the GRADE method, but this method is based on the quality of evidences and substantial end point , i.e. the overall survival. Even if the Authors have evidenced several limitations of the analyses ( surrogate markers, lack of control group,…) they still conclude that there are not differences in the “larger effect size”. Thanks for the comments, we clarified these aspects in the conclusion. Specific comments • The effect size should be better explained and an explicative table, reporting statistics for all the parameter considered, could be useful We are grateful for the reviewer’s comments, we already information regarding table 1, table 2 and supplemental material that explain raw data. In order to add information regarding effect sizes, according to reviewers suggestion we opted to create Graphs (Graph 1-4) to demonstrate effect sizes differences in Accelerated approval pathway and Breakthrough therapy designation. • With regard to the study design, have the statistic power and the sample size been considered? We included this information at the Methods session: “The studies were primarily descriptive, and we included all data available for lung cancer treatment in the period (2006-2018).” Thus, as we included all the information available of studies used to approval for lung cancer treatment, power calculation is not necessary. Attachments Attachment Submitted filename: Letter PLOS ONE - Review.docx https://doi.org/10.1371/journal.pone.0236345.r002
7 Jul 2020 Decision Letter - Erika Cecchin, Editor Comparison of FDA Accelerated vs Regular Pathway Approvals for Lung Cancer Treatments between 2006 and 2018 PONE-D-20-00807R1 Dear Dr. Bomfim Ribeiro, 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, Erika Cecchin 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 #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: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 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: (No Response) 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 #1: (No Response) 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 #1: (No Response) Reviewer #2: NO comments. The Authors answered the questions.................................................................... ............................................................................................................ ****** 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.0236345.r003
Formally Accepted
15 Jul 2020 Acceptance Letter - Erika Cecchin, Editor PONE-D-20-00807R1 Comparison of FDA Accelerated vs Regular Pathway Approvals for Lung Cancer Treatments between 2006 and 2018 Dear Dr. Ribeiro: 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. Erika Cecchin Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0236345.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .