The minimum effective concentration (MEC90) of ropivacaine for ultrasound-guided caudal block in anorectal surgery. A dose finding study

Xuehan Li; Jun Li; Pei Zhang; Huifei Deng; Mingan Yang; Hongbo He; Rurong Wang

doi:10.1371/journal.pone.0257283

Peer Review History

Original SubmissionOctober 15, 2020
19 May 2021 Decision Letter - Ehab Farag, Editor PONE-D-20-29940 The minimum effective concentration (MEC90) of ropivacaine for ultrasound-guided caudal block in anorectal surgery. A does finding study PLOS ONE Dear Dr. rurong wang 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. I would appreciate if pay careful attention in your response to the reviewer's comments. In addition, I would prefer if you add success rate in performing the block from first attempt, the duration of performing the block in each group and add in the limitation of the study that the block was performed in low BMI patients as this block could be difficult to perform in patients with high BMI. 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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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. 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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: Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance]. COMMENTS: Because this is a dose-finding study, there are not much to comment on [in context of statistical review]. For this purpose, design used (biased coin design up-and-down sequential method) is perfectly alright {though I do not have any first-hand experience of using this design, on the basis of as much I know, I can dare to say this}. Randomization procedure used [lines 14-17], I guess, is known as ‘two-arm-bandit problem in play the winner allocation rule’. Please confirm if my information is correct, kindly inform otherwise. You may please mention this, if true. You might have rightly used references 7 & 8 [published in very good journals, namely Statistics in medicine and Biometrics], to estimate assignment ‘probabilities’, the explanation given in lines 165-7 [If a patient had a successful block, the next subject was randomized with probability b=0.11 to the next lower concentration and 1-b=0.89 to the same concentration] seems to be insufficient in my opinion {particular readers would like know ‘how ‘b’ would serve your purpose? And ‘b’ is estimated after data collection}. In next line (by using same excellent reference) you say “To estimate MEC90, a minimum of 45 positive responses were required”, I wonder if that is enough? [because sample size is an important issue and though technical, little more is expected, I guess]. Male vs Female comparison in Table-1 {Characteristics of patients} was not irrelevant in my opinion [‘P’-value column]. To provide a description of baseline characteristics is entirely reasonable (since it is clearly important in assessing to whom the results of the trial can be applied), however, such statistical comparison [last ‘p-value’ column in Table 1] is not desirable at all. Purpose of Table-3 [Caudal epidural block characteristics and block complications of successful caudal block] is not understood. I think here also statistical comparison [last ‘p-value’ column in Table] may not be correct/desirable. Other than these minor revision points, the article is acceptable, in my opinion/assessment. ****** 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. Attachments Attachment Submitted filename: renamed_ce123.docx https://doi.org/10.1371/journal.pone.0257283.r001
Revision 1
7 Jul 2021 Author Response Response to Editor: 1. I would prefer if you add success rate in performing the block from first attempt, the duration of performing the block in each group and add in the limitation of the study that the block was performed in low BMI patients as this block could be difficult to perform in patients with high BMI. RESPONSE: See the highlighted text in the manuscript. It was around 15min of each block but we did not have detailed duration of performing the block in each group. REVISED TEXT: Of those successful blocks, there were 43 of 45 males and 42 of 45 females got success block at first attempt.(Line 260-261) Besides, all blocks in this study were performed in patients with BMI from 18 to 27 Kg/m2, which might limit the application in patients with high BMI. (Line 392-394) --- Response to reviewer #1: Because this is a dose-finding study, there are not much to comment on [in context of statistical review]. For this purpose, design used (biased coin design up-and-down sequential method) is perfectly alright {though I do not have any first-hand experience of using this design, on the basis of as much I know, I can dare to say this}. Randomization procedure used [lines 14-17], I guess, is known as ‘two-arm-bandit problem in play the winner allocation rule’. Please confirm if my information is correct, kindly inform otherwise. You may please mention this, if true. RESPONSE: We checked the articles reporting the biased up and down method we applied, and there is no clue of the relationship between this method and two-arm-bandit problem in play the winner allocation rule’. We apologize for the limitation of our knowledge and we cannot answer this question. We would like to study this if Pro. Reviewer give us a clue. You might have rightly used references 7 & 8 [published in very good journals, namely Statistics in medicine and Biometrics], to estimate assignment ‘probabilities’, the explanation given in lines 165-7 [If a patient had a successful block, the next subject was randomized with probability b=0.11 to the next lower concentration and 1-b=0.89 to the same concentration] seems to be insufficient in my opinion {particular readers would like know ‘how ‘b’ would serve your purpose? And ‘b’ is estimated after data collection}. RESPONSE: Thanks for the reviewer’s comment, we now revised it, see highlighted text. Following Stylianou et al.7, we randomize the next patient with probability b=(1-T)/T to the next lower volume and 1-b=0.89 to the same volume, where T=0.90 in the MEC90 and T=0.5 in the MEC50. REVISED TEXT: Following Stylianou et al. (1,2), we randomize the next patient with probability b=(1-T)/T to the next lower volume and 1-b=0.89 to the same volume, where T=0.90 in the MEV90. (Line 165-167) In next line (by using same excellent reference) you say “To estimate MEC90, a minimum of 45 positive responses were required”, I wonder if that is enough? [because sample size is an important issue and though technical, little more is expected, I guess]. RESPONSE: We now revise it, see highlighted text. REVISED TEXT: Stylianou et al. (1,2) performed extensive trials and found that the estimated probability of toxicity associated with the recommended dose is stabilized with a sample size of at least 20 and best at over 40. Following this, we choose the sample size of 45 to accommodate potential dropout. (Line 170-173) Male vs Female comparison in Table-1 {Characteristics of patients} was not irrelevant in my opinion [‘P’-value column]. To provide a description of baseline characteristics is entirely reasonable (since it is clearly important in assessing to whom the results of the trial can be applied), however, such statistical comparison [last ‘p-value’ column in Table 1] is not desirable at all. Purpose of Table-3 [Caudal epidural block characteristics and block complications of successful caudal block] is not understood. I think here also statistical comparison [last ‘p-value’ column in Table] may not be correct/desirable. RESPONSE: Sorry for the confusion. We now delete the “p value” column of Table 1 and Table 3. Table 3 was provided for the possible guidance of clinical practice. References 1. Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics. 2002;58(1):171-7. 2. Stylianou M, Proschan M, Flournoy N. Estimating the probability of toxicity at the target dose following an up-and-down design. Statistics in medicine. 2003;22(4):535-43. https://doi.org/10.1371/journal.pone.0257283.r002
31 Aug 2021 Decision Letter - Ehab Farag, Editor The minimum effective concentration (MEC90) of ropivacaine for ultrasound-guided caudal block in anorectal surgery. A does finding study PONE-D-20-29940R1 Dear Dr.Rurong Wang 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, Ehab Farag, MD FRCA FASA Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0257283.r003
Formally Accepted
9 Sep 2021 Acceptance Letter - Ehab Farag, Editor PONE-D-20-29940R1 The minimum effective concentration (MEC90) of ropivacaine for ultrasound-guided caudal block in anorectal surgery. A does finding study Dear Dr. Wang: 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. Ehab Farag Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0257283.r004

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