Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies

Nisaharan Srikandarajah; Adam Noble; Simon Clark; Martin Wilby; Brian J. C. Freeman; Michael G. Fehlings; Paula R. Williamson; Tony Marson

doi:10.1371/journal.pone.0225907

Peer Review History

Original SubmissionJuly 1, 2019
18 Sep 2019 Decision Letter - Rodrigo Romao, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-19-18530 Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies PLOS ONE Dear Mr Srikandarajah, 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. We would appreciate receiving your revised manuscript by Nov 02 2019 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. 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Please include a copy of the interview guide used in the study, in both the original language and English, as Supporting Information, or include a citation if it has been published previously. 3. One of the noted authors is a group or consortium [CES Consensus Group]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. 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 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: This study was clearly described in terms of relevance, methodology and results. It appears to be very novel and highly relevant for future research on patients with CES. I found it interesting that bladder dysfunction scored so highly with regards to importance as a COS. Reviewer #2: Thank you for asking me to review this submitted manuscript. The authors report an international patient and healthcare professional consensus and propose a Cauda Equina Syndrome Core Outcome Set (CESCOS). Some comments: 1. Overall, the authors seem to be appropriately building on their previous work [(Spine (Phila Pa 1976). 2018 Sep 1;43(17):E1005-E1013. doi: 10.1097/BRS.0000000000002605)], where significant heterogeneity in outcomes reported for studies after surgery for CES patients indicated a need for the development of a core outcome set. 2. Abstract: reasonable depiction of the manuscript. 3. Introduction: fine 4. Methods: described logically and comprehensively. 5. Results: - In "Protocol Deviations", the first sentence is difficult to understand due to the word "out". Please rephrase. - The first two subheadings ('Protocol deviations' and 'The List of Outcomes') seem to be more appropriately placed in the Methods section. - please reserve the Results section for Results alone. - In reporting the "years of practice" amongst HCP participants, do the authors include years in training? - Can the authors clarify how many respondents were trainees vs specialists? - Their later comment in the discussion that "63% had 10 years or more experience" is noted, but it remains unclear whether the 10 is post-residency training. 6. Discussion: - appropriate discussion of the consensus group composition. - the authors have omitted to cite a recent study (perhaps because this was published after the present study's submission) which seemingly reported the largest cohort of patients with CES investigated for long-term outcomes using validated questionnaires. Please discuss the findings and choice of questionnaires used, and how your COS might improve this. [Hazelwood JE et al. An assessment of patient-reported long-term outcomes following surgery for cauda equina syndrome. Acta Neurochir (Wien). 2019 Sep;161(9):1887-1894. doi: 10.1007/s00701-019-03973-7. Epub 2019 Jul 1.] - Limitations: fair discussion. - can the authors discuss the potential uptake of their recommended COS, incl the length of time required to obtain the COS data and any pragmatic difficulties. 7. Conclusion: - 16 outcomes that are critical to key stakeholders have been identified. How 8. This constitutes a piece of hard work and the authors are congratulated in its design and execution. Looking forward to a quick return addressing the points made. ****** 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: Ashley Cox 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. 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Revision 1
11 Nov 2019 Author Response Response to Reviewers PONE-D-19-18530 Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies PLOS ONE All comments from the journal and reviewers have been highlighted in bold and addressed below in normal script. Journal 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.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 This has been done. 2. Please include a copy of the interview guide used in the study, in both the original language and English, as Supporting Information, or include a citation if it has been published previously. This has been done: “Semi-structured interviews were conducted with a topic guide (S1 File) and involved patients’ describing their experience of CES in a chronological manner to ascertain the relevant outcomes and the lived experience of the condition.” 3. One of the noted authors is a group or consortium [CES Consensus Group]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. This has been deleted from the author byline. In the acknowledgements, I have included patient and healthcare collaborators for the consensus meeting. Addressing reviewer comments Reviewer #1: This study was clearly described in terms of relevance, methodology and results. It appears to be very novel and highly relevant for future research on patients with CES. I found it interesting that bladder dysfunction scored so highly with regards to importance as a COS. Thank you for these comments. Reviewer #2: Thank you for asking me to review this submitted manuscript. The authors report an international patient and healthcare professional consensus and propose a Cauda Equina Syndrome Core Outcome Set (CESCOS). Some comments: 1. Overall, the authors seem to be appropriately building on their previous work [(Spine (Phila Pa 1976). 2018 Sep 1;43(17):E1005-E1013. doi: 10.1097/BRS.0000000000002605)], where significant heterogeneity in outcomes reported for studies after surgery for CES patients indicated a need for the development of a core outcome set. 2. Abstract: reasonable depiction of the manuscript. 3. Introduction: fine 4. Methods: described logically and comprehensively. 5. Results: - In "Protocol Deviations", the first sentence is difficult to understand due to the word "out". Please rephrase. This sentence has been changed from this: “As mentioned before, the definition of consensus out was changed for the Delphi survey with agreement from the study team. There were no other deviations from the protocol.” To this: “As mentioned before, the definition for an outcome not to be included (termed “consensus out” in Table 1) was changed for the Delphi survey with agreement from the study team. There were no other deviations from the protocol.” - The first two subheadings ('Protocol deviations' and 'The List of Outcomes') seem to be more appropriately placed in the Methods section. - please reserve the Results section for Results alone. Protocol deviations are to be reported in the results section in accordance with item 11 in Table 1 of the Core Outcome Set-STAndards for Reporting (COS-STAR)(1) guidelines. The List of Outcomes has now been removed from the results and implemented into the paragraph titled “Information sources” in Methods as per your comments and in line with item 6a and 6b of the COS-STAR reporting guidelines. References Kirkham JJ, Gorst S, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, Moher D, Schmitt J, Tugwell P, Tunis S. Core outcome set–STAndards for reporting: the COS-STAR statement. PLoS medicine. 2016 Oct 18;13(10):e1002148. - In reporting the "years of practice" amongst HCP participants, do the authors include years in training? No. It is the years of practice as a consultant or attending surgeon after Board certification. This has now been highlighted in brackets within the Table 3 heading for clarification as “Years of practice (as a consultant/ attending after board certification).” - Can the authors clarify how many respondents were trainees vs specialists? All were specialists. No trainees were included. This was addressed as per the question above. - Their later comment in the discussion that "63% had 10 years or more experience" is noted, but it remains unclear whether the 10 is post-residency training. Yes 10 years’ post residency training. Sentence changed for clarification to: “Most HCPs taking part in the Delphi were of a surgical background and 63% had 10 years or more experience after board certification as a consultant/ attending or the equivalent.” 6. Discussion: - appropriate discussion of the consensus group composition. This was added to the results section under “consensus meeting”: “Of the 18 HCPs at the consensus meeting, 10 were surgeons involved in acute CES management and 8 were doctors and allied HCPs involved in the longer-term care and rehabilitation of CES patients. In the patient group, there was an equal spread of patients in the years since diagnosis of CES (<2: 5, ≥2<5: 4, ≥5<10: 6 and ≥10: 1).” This was added in the discussion: “As mentioned in the results, over half of the HCPs attending the consensus meeting were involved in acute management and the rest involved in longer term care and rehabilitation of CES patients, which would be reflective of a group of HCPs that manage CES patients in the short and long term from diagnosis. There was an equal spread of patients in the years since CES diagnosis, which would have also facilitated prioritisation of short and long term outcomes.” - the authors have omitted to cite a recent study (perhaps because this was published after the present study's submission) which seemingly reported the largest cohort of patients with CES investigated for long-term outcomes using validated questionnaires. Please discuss the findings and choice of questionnaires used, and how your COS might improve this. [Hazelwood JE et al. An assessment of patient-reported long-term outcomes following surgery for cauda equina syndrome. Acta Neurochir (Wien). 2019 Sep;161(9):1887-1894. doi: 10.1007/s00701-019-03973-7. Epub 2019 Jul 1.] Thank you for bringing us to the attention of this study. This has now been referenced in the discussion: “A prospective study of long term outcomes after surgery for 46 CES patients had a mean follow up of 43 months. Validated questionnaires and unvalidated semi structured interviews were used to assess long term outcomes of bladder, bowel, sexual and physical function. Not all the outcomes in the CESCOS have been measured. For example, perineal sensation, sensation in genitals, leg muscle strength, pain due to abnormal sensation or non-painful stimulus and complications from the operation, were not measured. For the outcomes that were measured, there has not been a transparent consensus process(2) regarding the choice of these outcome measurement instruments. In Table 5 of a systematic literature review(3), it was shown that between studies, there is a lack of uniformity in the assessments used for the outcomes in CES, which makes it difficult to synthesise the results for meaningful analysis. The CESCOS highlights the outcomes for which this process must be undertaken in a transparent and methodologically sound manner.” References Prinsen CA, Vohra S, Rose MR, Boers M, Tugwell P, Clarke M, Williamson PR, Terwee CB. How to select outcome measurement instruments for outcomes included in a “Core Outcome Set”–a practical guideline. Trials. 2016 Dec;17(1):449. Srikandarajah N, Wilby M, Clark S, Noble A, Williamson P, Marson T. Outcomes reported after surgery for cauda equina syndrome: a systematic literature review. Spine. 2018 Sep 1;43(17):E1005. - Limitations: fair discussion. - can the authors discuss the potential uptake of their recommended COS, incl the length of time required to obtain the COS data and any pragmatic difficulties. This has been added to the discussion: There is little research into the uptake of core outcome sets in comparison to randomised trials and systematic reviews as there are a relatively smaller number of them(4). A review of the rheumatoid arthritis COS established in 1994 showed that 81% of trials between 2002 and 2016 were reporting it (5). Implementation is an important aspect to help promote uptake and to aid this the CESCOS is registered on the COMET database, is published and will be presented at meetings and relevant HCP, patient and research funding bodies will be informed. In the qualitative interviews, Delphi survey and consensus meeting for the CESCOS study, patients were keen and willing to be involved. This may be a reflection that it is a rare syndrome so any attention or further research for the condition is actively engaged and welcomed by them suggesting the burden of data collection is not an issue with this patient group. A study reviewing the long-term outcomes after spinal surgery for CES showed that there was a real need for HCPs to spend sufficient time discussing the difficult issues and delivering prognostic information to patients regarding their outcomes(6). This highlights the importance of recording and reporting the CESCOS outcomes for future research studies. Currently, a multicentre prospective observational cohort study in CES is using the CESCOS(7) for its follow up data collection. The pragmatic difficulties of data measurement will be explored here. The COS should be reviewed in the future to see if any outcomes need to be added or subtracted(19). The aim is to do this in five years to analyse uptake in CES research studies. References Kirkham JJ, Clarke M, Williamson PR. A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials. gov: findings from a review of randomised controlled trials of rheumatoid arthritis. bmj. 2017 May 17;357:j2262. Woodfield J, Hoeritzauer I, Jamjoom AA, Pronin S, Srikandarajah N, Poon M, Roy H, Demetriades AK, Sell P, Eames N, Statham PF. Understanding cauda equina syndrome: protocol for a UK multicentre prospective observational cohort study. BMJ open. 2018 Dec 1;8(12):e025230. Korse NS, Veldman AB, Peul WC, Vleggeert-Lankamp CL. The long term outcome of micturition, defecation and sexual function after spinal surgery for cauda equina syndrome. PLoS ONE. 2017;12(4):e0175987. 7. Conclusion: - 16 outcomes that are critical to key stakeholders have been identified. How How this has been identified is explained in the methods and the results of this paper. There is also a protocol which we have referenced in the manuscript. 8. This constitutes a piece of hard work and the authors are congratulated in its design and execution. Looking forward to a quick return addressing the points made. Thank you for these comments. I hope the answers and corrections made are satisfactory. 1. Kirkham JJ, Gorst S, Altman DG, Blazeby JM, Clarke M, Devane D, et al. Core outcome set–STAndards for reporting: the COS-STAR statement. PLoS medicine. 2016;13(10):e1002148. 2. Prinsen CA, Vohra S, Rose MR, Boers M, Tugwell P, Clarke M, et al. How to select outcome measurement instruments for outcomes included in a “Core Outcome Set”–a practical guideline. Trials. 2016;17(1):449. 3. Srikandarajah N, Wilby M, Clark S, Noble A, Williamson P, Marson T. Outcomes reported after surgery for Cauda Equina Syndrome: A Systematic Literature Review. Spine. 2018. 4. Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET handbook: version 1.0. Trials. 2017;18(3):280. 5. Kirkham JJ, Clarke M, Williamson PR. A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials. gov: findings from a review of randomised controlled trials of rheumatoid arthritis. Bmj. 2017;357:j2262. 6. Korse NS, Veldman AB, Peul WC, Vleggeert-Lankamp CL. The long term outcome of micturition, defecation and sexual function after spinal surgery for cauda equina syndrome. PLoS ONE. 2017;12(4):e0175987. 7. Woodfield J, Hoeritzauer I, Jamjoom AA, Pronin S, Srikandarajah N, Poon M, et al. Understanding cauda equina syndrome: protocol for a UK multicentre prospective observational cohort study. BMJ open. 2018;8(12):e025230. Attachments Attachment Submitted filename: Response to reviewers_final.docx https://doi.org/10.1371/journal.pone.0225907.r002
15 Nov 2019 Decision Letter - Rodrigo Romao, Editor Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies PONE-D-19-18530R1 Dear Dr. Srikandarajah, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Rodrigo Romao Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have adequately addressed the questions and comments posed by the reviewers. Reviewers' comments: https://doi.org/10.1371/journal.pone.0225907.r003
Formally Accepted
18 Dec 2019 Acceptance Letter - Rodrigo Romao, Editor PONE-D-19-18530R1 Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies Dear Dr. Srikandarajah: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Rodrigo Romao Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0225907.r004

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