Reviewer’ s report
Title: Rotational thrombelastometry (ROTEM) improves hemostasis assessment compared to
conventional coagulation test in ACLF and Non-ACLF patients
Version: 0Date: 09 May 2020
Reviewer's report:
Thank you for the opportunity to review this article, a cross-sectional study of adults with cirrhosis
investigating rotational thromboelastometry (ROTEM) results compared to conventionalcoagulation tests (CCTs) in patients with cirrhosis without acute-on-chronic liver failure (ACLF)(n = 55) and ACLF (n = 22). My comments are as follows:
*Although some data elements appear cross-sectional, this does not appear to be a cross-sectional
study especially if patients are followed until development of clinical outcome (bleeding event andsurvival). This would specifically be a cohort study. Whether it is a retrospective/historical or aprospective cohort study depends on when the investigators extracted the patient data. As patientconsent was obtained on hospitalization it appears that this would be a prospective cohort study.*The introduction should have more details at the end regarding the aims of the study, andhypothesis(es) to be studied, because it seems like there are two: (a) assessment of testcharacteristics (CCT versus ROTEM) including agreement, and (b) prospective assessment of testperformance based on patient clinical outcomes (though it appears that it was only assessed inthose with ACLF?*I recommend adding to the methods section details regarding assessment of patient outcomes,how these were defined, and other applicable details, as there is much detail regarding thecoagulation testing but not the outcomes assessments. To this effect the authors should consider
making subtitles for their manuscript to separate the two primary aims of their manuscript of test
assessment and outcome assessment.*Recommend these results be reviewed by a biostatistician: there are examples of questions ofwhether certain statistical tests are valid, or whether they were reported corrected. For example,Table 1 for categorical variables (Child-Pugh [CP] class, ACLF grade, bleeding events, etc.) thereis an overall p-value reported, but also individual p-values for each subgroup, which I would notexpect to be reported (SPSS puts out these values but they should not be reported). Related is thatgiven the low numbers of events, a chi-square test should not be used (rather, Fisher's exact testshould be used), and thus a chi-square test is an invalid test anyways. There are other statisticalmethodological questions that I have including whether parametric tests were valid to begin withfor certain continuous variables (such as Model of End-Stage Liver Disease [MELD] score andCP. For this reason, I believe evaluation of these results as well as reporting should be performedby a biostatistician.*I believe it an overstatement to conclude from this study that ROTEM is superior to CCT inassessing coagulation status because it is unclear how this was assessed in this study other than asubgroup analysis of the patients with ACLF and associated bleeding events. The best way to forformally assess performance is to establish cutoffs for positive and negative result, and then followthose specific groups to outcome. That requires calibration, refinement, and then validation, which
is not present in this study. Thus, I recommend removing statements making such a claim, or the
authors would need to be clearer regarding how this was assessed in this study.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I recommend additional statistical reviewQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Reviewer’ s report
Title: Rotational thrombelastometry (ROTEM) improves hemostasis assessment compared to
conventional coagulation test in ACLF and Non-ACLF patients
Version: 0Date: 09 May 2020
Reviewer's report:
Thank you for the opportunity to review this article, a cross-sectional study of adults with cirrhosis
investigating rotational thromboelastometry (ROTEM) results compared to conventionalcoagulation tests (CCTs) in patients with cirrhosis without acute-on-chronic liver failure (ACLF)(n = 55) and ACLF (n = 22). My comments are as follows:
*Although some data elements appear cross-sectional, this does not appear to be a cross-sectional
study especially if patients are followed until development of clinical outcome (bleeding event andsurvival). This would specifically be a cohort study. Whether it is a retrospective/historical or aprospective cohort study depends on when the investigators extracted the patient data. As patientconsent was obtained on hospitalization it appears that this would be a prospective cohort study.*The introduction should have more details at the end regarding the aims of the study, andhypothesis(es) to be studied, because it seems like there are two: (a) assessment of testcharacteristics (CCT versus ROTEM) including agreement, and (b) prospective assessment of testperformance based on patient clinical outcomes (though it appears that it was only assessed inthose with ACLF?*I recommend adding to the methods section details regarding assessment of patient outcomes,how these were defined, and other applicable details, as there is much detail regarding thecoagulation testing but not the outcomes assessments. To this effect the authors should consider
making subtitles for their manuscript to separate the two primary aims of their manuscript of test
assessment and outcome assessment.*Recommend these results be reviewed by a biostatistician: there are examples of questions ofwhether certain statistical tests are valid, or whether they were reported corrected. For example,Table 1 for categorical variables (Child-Pugh [CP] class, ACLF grade, bleeding events, etc.) thereis an overall p-value reported, but also individual p-values for each subgroup, which I would notexpect to be reported (SPSS puts out these values but they should not be reported). Related is thatgiven the low numbers of events, a chi-square test should not be used (rather, Fisher's exact testshould be used), and thus a chi-square test is an invalid test anyways. There are other statisticalmethodological questions that I have including whether parametric tests were valid to begin withfor certain continuous variables (such as Model of End-Stage Liver Disease [MELD] score andCP. For this reason, I believe evaluation of these results as well as reporting should be performedby a biostatistician.*I believe it an overstatement to conclude from this study that ROTEM is superior to CCT inassessing coagulation status because it is unclear how this was assessed in this study other than asubgroup analysis of the patients with ACLF and associated bleeding events. The best way to forformally assess performance is to establish cutoffs for positive and negative result, and then followthose specific groups to outcome. That requires calibration, refinement, and then validation, which
is not present in this study. Thus, I recommend removing statements making such a claim, or the
authors would need to be clearer regarding how this was assessed in this study.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I recommend additional statistical reviewQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Please review this paper.
user
Reviewer’ s report
Title: Rotational thrombelastometry (ROTEM) improves hemostasis assessment compared to
conventional coagulation test in ACLF and Non-ACLF patients
Version: 0Date: 09 May 2020
Reviewer's report:
Thank you for the opportunity to review this article, a cross-sectional study of adults with cirrhosis
investigating rotational thromboelastometry (ROTEM) results compared to conventionalcoagulation tests (CCTs) in patients with cirrhosis without acute-on-chronic liver failure (ACLF)(n = 55) and ACLF (n = 22). My comments are as follows:
*Although some data elements appear cross-sectional, this does not appear to be a cross-sectional
study especially if patients are followed until development of clinical outcome (bleeding event andsurvival). This would specifically be a cohort study. Whether it is a retrospective/historical or aprospective cohort study depends on when the investigators extracted the patient data. As patientconsent was obtained on hospitalization it appears that this would be a prospective cohort study.*The introduction should have more details at the end regarding the aims of the study, andhypothesis(es) to be studied, because it seems like there are two: (a) assessment of testcharacteristics (CCT versus ROTEM) including agreement, and (b) prospective assessment of testperformance based on patient clinical outcomes (though it appears that it was only assessed inthose with ACLF?*I recommend adding to the methods section details regarding assessment of patient outcomes,how these were defined, and other applicable details, as there is much detail regarding thecoagulation testing but not the outcomes assessments. To this effect the authors should consider
making subtitles for their manuscript to separate the two primary aims of their manuscript of test
assessment and outcome assessment.*Recommend these results be reviewed by a biostatistician: there are examples of questions ofwhether certain statistical tests are valid, or whether they were reported corrected. For example,Table 1 for categorical variables (Child-Pugh [CP] class, ACLF grade, bleeding events, etc.) thereis an overall p-value reported, but also individual p-values for each subgroup, which I would notexpect to be reported (SPSS puts out these values but they should not be reported). Related is thatgiven the low numbers of events, a chi-square test should not be used (rather, Fisher's exact testshould be used), and thus a chi-square test is an invalid test anyways. There are other statisticalmethodological questions that I have including whether parametric tests were valid to begin withfor certain continuous variables (such as Model of End-Stage Liver Disease [MELD] score andCP. For this reason, I believe evaluation of these results as well as reporting should be performedby a biostatistician.*I believe it an overstatement to conclude from this study that ROTEM is superior to CCT inassessing coagulation status because it is unclear how this was assessed in this study other than asubgroup analysis of the patients with ACLF and associated bleeding events. The best way to forformally assess performance is to establish cutoffs for positive and negative result, and then followthose specific groups to outcome. That requires calibration, refinement, and then validation, which
is not present in this study. Thus, I recommend removing statements making such a claim, or the
authors would need to be clearer regarding how this was assessed in this study.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I recommend additional statistical reviewQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
assistant