Genetic testing offer for inherited neuromuscular diseases within the EURO-NMD reference network: A European survey study

Borut Peterlin; Francesca Gualandi; Ales Maver; Serenella Servidei; Silvère M. van der Maarel; Francoise Lamy; Alexander Mejat; Teresinha Evangelista; Alessandra Ferlini

doi:10.1371/journal.pone.0239329

Peer Review History

Original SubmissionMay 18, 2020
28 Jul 2020 Decision Letter - Alfred S Lewin, Editor PONE-D-20-14793 Genetic testing offer for inherited neuromuscular diseases within the EURO-NMD reference network: a European survey study. PLOS ONE Dear Dr. Ferlini, 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 single expert reviewer felt that your paper was well written and that your finds support your conclusions. This reviewer did make useful suggestions for its improvement. Please submit your revised manuscript by Sep 11 2020 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. 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, Alfred S Lewin, Ph.D. 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 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 Additional Editor Comments (if provided): [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 ******** 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 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 ****** 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 ****** 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: This is an interesting report that outlines the genetic diagnostics of inherited neuromuscular diseases within the EURO-NMD European Reference Network (ERN). The results are interesting but not unexpected. I have a few comments. 1. In the Abstract, in the first paragraph, the authors talk about the collection of “information about the diffusion/distribution of genetic testing across 61 ERN healthcare providers.” It is not clear to me what the authors mean by “diffusion” of genetic testing. They probably mean the “availability” of genetic testing, but I am not sure. Using a different word will make it clear to the readers of this paper. 2. In the Introduction, line 91, the statement about lack of reimbursement is interesting given that all the surveyed centers providing the testing were public institutions. You would expect a government-run healthcare system to cover the expenses. I think this is an interesting topic, and hence it might be useful for the authors to elaborate on that and to compare it, for example, to private institutions. It would also be interesting to know the impact of lack of reimbursement on the capacity of these laboratories to offer the testing ordered by clinicians. 3. The paper is well written; however, it feels as if sometimes the information is repeated. It might be useful to avoid repetition in the paper. For example, in the Results section and under EUGT Orphanet Related Data, the authors have selected a number of diseases such as SMA, DMD, Pompe’s disease, limb-girdle muscular dystrophies, and transthyretin related peripheral neuropathy, to describe specific data about these diseases. They do the same in the Discussion section of the paper in more detail. My advice would be to present the information only in one section, perhaps the Results section, and make a few comments in the Discussion about this group of diseases. 4. The Barriers to Testing section is very interesting. Again, the lack of reimbursement seems to be a main hurdle, followed by lack of experience and lack of professional guidelines. It might be interesting for the readers to know which are the testing sites within ERN. It is not clear from this paper whether there is a central agency that certifies these laboratories, as happens in other countries, like the USA. Are these clinical or research-based labs? 5. In the section under Databases, the authors do not list commonly used databases in other parts of the world, like the Exome Variant Server database, the NIH SNP database, and others, and I do not understand the reason for that. 6. Under Disease Specific Data, in the SMA paragraph, the authors observe that only 17.7% of the centers also tested SMN2 gene copy number. Is this because of lack of technical expertise? It is not clear. ****** 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 [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.0239329.r001
Revision 1
1 Sep 2020 Author Response Review Comments to the Author Reviewer #1: This is an interesting report that outlines the genetic diagnostics of inherited neuromuscular diseases within the EURO-NMD European Reference Network (ERN). The results are interesting but not unexpected. I have a few comments. 1. In the Abstract, in the first paragraph, the authors talk about the collection of “information about the diffusion/distribution of genetic testing across 61 ERN healthcare providers.” It is not clear to me what the authors mean by “diffusion” of genetic testing. They probably mean the “availability” of genetic testing, but I am not sure. Using a different word will make it clear to the readers of this paper. We thank the reviewer for this comment. It is right, we meant availability, we have rephrased the sentence. 2. In the Introduction, line 91, the statement about lack of reimbursement is interesting given that all the surveyed centers providing the testing were public institutions. You would expect a government-run healthcare system to cover the expenses. I think this is an interesting topic, and hence it might be useful for the authors to elaborate on that and to compare it, for example, to private institutions. It would also be interesting to know the impact of lack of reimbursement on the capacity of these laboratories to offer the testing ordered by clinicians. In line with the reviewer’s suggestion we elaborated on the financing issues related to NGS testing by expanding the concept in the Introduction and implementing Discussion. 3. The paper is well written; however, it feels as if sometimes the information is repeated. It might be useful to avoid repetition in the paper. For example, in the Results section and under EUGT Orphanet Related Data, the authors have selected a number of diseases such as SMA, DMD, Pompe’s disease, limb-girdle muscular dystrophies, and transthyretin related peripheral neuropathy, to describe specific data about these diseases. They do the same in the Discussion section of the paper in more detail. My advice would be to present the information only in one section, perhaps the Results section, and make a few comments in the Discussion about this group of diseases. We agree with the reviewer and we amended that accordingly with shorten and rephrased paragraphs. 4. The Barriers to Testing section is very interesting. Again, the lack of reimbursement seems to be a main hurdle, followed by lack of experience and lack of professional guidelines. It might be interesting for the readers to know which are the testing sites within ERN. It is not clear from this paper whether there is a central agency that certifies these laboratories, as happens in other countries, like the USA. Are these clinical or research-based labs? Thanks for this comment; we have added a sentence specifying what the referee requested. 5. In the section under Databases, the authors do not list commonly used databases in other parts of the world, like the Exome Variant Server database, the NIH SNP database, and others, and I do not understand the reason for that. We thank the reviewer for his comment. The authors were trying to define the problems of the existing databases and the diversity of data that is collected in each one. By no means had we wanted to exclude databases in other regions of the world, we have tried to use examples that were best known to us and tools that in the last years have received wide approval in Europe such as the HPO or the FAIR principles. 6. Under Disease Specific Data, in the SMA paragraph, the authors observe that only 17.7% of the centers also tested SMN2 gene copy number. Is this because of lack of technical expertise? It is not clear. The referee is right the sentence was not clear. We have modified the SMA paragraphs. Attachments Attachment Submitted filename: RESPONSE TO REFEREES 28.8.20.docx https://doi.org/10.1371/journal.pone.0239329.r002
4 Sep 2020 Decision Letter - Alfred S Lewin, Editor Genetic testing offer for inherited neuromuscular diseases within the EURO-NMD reference network: a European survey study. PONE-D-20-14793R1 Dear Dr. Ferlini, 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, Alfred S Lewin, Ph.D. Section Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0239329.r003
Formally Accepted
9 Sep 2020 Acceptance Letter - Alfred S Lewin, Editor PONE-D-20-14793R1 Genetic testing offer for inherited neuromuscular diseases within the EURO-NMD reference network: a European survey study. Dear Dr. Ferlini: 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. Alfred S Lewin Section Editor PLOS ONE https://doi.org/10.1371/journal.pone.0239329.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 .