Reviewer ’s report  
 
Title: What is impact of Nonsteroidal anti -inflammatory drugs  in the prevention of post -
endoscopic retrograde cholangiopancreatography pancreatitis: a meta -analysis of randomized 
controlled trials  
 
Version: 0 Date: 07 Jan 2018  
 
Reviewer: Mark Berner Hansen  
 
Reviewer's report:  
 
Indeed the topic for this paper is relevant and I congratulate you authors for your attempt to tease 
out some important aspects of NSAID's ( patient segment, route, timing, type of NSAID etc.) for 
PEP via this metaanalysis.  
As previous published analysis (based on fewer studies and patient numbers) on this topic, your 
analysis also provides further support for some clinical relevant effect of NSAIDs in prevention 
of PEP and its outcome.  
According the purpose and methods of your paper are appropriate in general, although I am not 
able to fully judge the statistical details and potential pitfalls/errors. The paper is well -balanced 
and presented as such. Your data show efficacy based on mainly RR data. As you point out - the 
overall effect is however marginal for both average and high -risk ERCP patients. The varying 
standard of care (fluids ? pain medication etc), definition of severity of PEP and  the lacking info 
on doses (incl. regime, pharmacokinetics and dose -response relationships) is an important 
missing part of the equation. The conclusions points to various efficacy based on timing and 
route of administration and maybe even for which kind o f NSAID used is premature in my 
opinion and obviously there are some theoretical unclear results as you point out. I think the 
metaanalysis data are NOT convincing/strong enough to conclude anything for these topics and I 
would suggest you to revise paper as such - especially the discussion section and conclusions as 
such. Only a head -to-head 3 -4 arm properly powered RCTs would be able to answer such 
questions. This metaanalysis outlines some important questions  we need to answer for NSAIDs 
for PEP and esp ecially scientific clinical biomarker data and rationale for mode of action and 
pharmacokinetic -dynamics is needed.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments  to the authors.  
 
Yes 
 
  
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comm ents to the authors.  
 
No 
 
Are 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 further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of compe ting 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 this  
manuscript, 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 relatin g 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.  
 
No competing confl icting interests from my side  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I uplo ad will be posted on the website along with the authors'  
responses.  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/ ). I understand that any comments 
which I do  not wish to be included in my named report can be included as confidential comments 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: What is impact of Nonsteroidal anti -inflammatory drugs  in the prevention of post -
endoscopic retrograde cholangiopancreatography pancreatitis: a meta -analysis of randomized 
controlled trials  
 
Version: 0 Date: 07 Jan 2018  
 
Reviewer: Mark Berner Hansen  
 
Reviewer's report:  
 
Indeed the topic for this paper is relevant and I congratulate you authors for your attempt to tease 
out some important aspects of NSAID's ( patient segment, route, timing, type of NSAID etc.) for 
PEP via this metaanalysis.  
As previous published analysis (based on fewer studies and patient numbers) on this topic, your 
analysis also provides further support for some clinical relevant effect of NSAIDs in prevention 
of PEP and its outcome.  
According the purpose and methods of your paper are appropriate in general, although I am not 
able to fully judge the statistical details and potential pitfalls/errors. The paper is well -balanced 
and presented as such. Your data show efficacy based on mainly RR data. As you point out - the 
overall effect is however marginal for both average and high -risk ERCP patients. The varying 
standard of care (fluids ? pain medication etc), definition of severity of PEP and  the lacking info 
on doses (incl. regime, pharmacokinetics and dose -response relationships) is an important 
missing part of the equation. The conclusions points to various efficacy based on timing and 
route of administration and maybe even for which kind o f NSAID used is premature in my 
opinion and obviously there are some theoretical unclear results as you point out. I think the 
metaanalysis data are NOT convincing/strong enough to conclude anything for these topics and I 
would suggest you to revise paper as such - especially the discussion section and conclusions as 
such. Only a head -to-head 3 -4 arm properly powered RCTs would be able to answer such 
questions. This metaanalysis outlines some important questions  we need to answer for NSAIDs 
for PEP and esp ecially scientific clinical biomarker data and rationale for mode of action and 
pharmacokinetic -dynamics is needed.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments  to the authors.  
 
Yes 
 
  
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comm ents to the authors.  
 
No 
 
Are 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 further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of compe ting 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 this  
manuscript, 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 relatin g 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.  
 
No competing confl icting interests from my side  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I uplo ad will be posted on the website along with the authors'  
responses.  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/ ). I understand that any comments 
which I do  not wish to be included in my named report can be included as confidential comments 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: What is impact of Nonsteroidal anti -inflammatory drugs  in the prevention of post -
endoscopic retrograde cholangiopancreatography pancreatitis: a meta -analysis of randomized 
controlled trials  
 
Version: 0 Date: 07 Jan 2018  
 
Reviewer: Mark Berner Hansen  
 
Reviewer's report:  
 
Indeed the topic for this paper is relevant and I congratulate you authors for your attempt to tease 
out some important aspects of NSAID's ( patient segment, route, timing, type of NSAID etc.) for 
PEP via this metaanalysis.  
As previous published analysis (based on fewer studies and patient numbers) on this topic, your 
analysis also provides further support for some clinical relevant effect of NSAIDs in prevention 
of PEP and its outcome.  
According the purpose and methods of your paper are appropriate in general, although I am not 
able to fully judge the statistical details and potential pitfalls/errors. The paper is well -balanced 
and presented as such. Your data show efficacy based on mainly RR data. As you point out - the 
overall effect is however marginal for both average and high -risk ERCP patients. The varying 
standard of care (fluids ? pain medication etc), definition of severity of PEP and  the lacking info 
on doses (incl. regime, pharmacokinetics and dose -response relationships) is an important 
missing part of the equation. The conclusions points to various efficacy based on timing and 
route of administration and maybe even for which kind o f NSAID used is premature in my 
opinion and obviously there are some theoretical unclear results as you point out. I think the 
metaanalysis data are NOT convincing/strong enough to conclude anything for these topics and I 
would suggest you to revise paper as such - especially the discussion section and conclusions as 
such. Only a head -to-head 3 -4 arm properly powered RCTs would be able to answer such 
questions. This metaanalysis outlines some important questions  we need to answer for NSAIDs 
for PEP and esp ecially scientific clinical biomarker data and rationale for mode of action and 
pharmacokinetic -dynamics is needed.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments  to the authors.  
 
Yes 
 
  
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comm ents to the authors.  
 
No 
 
Are 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 further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of compe ting 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 this  
manuscript, 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 relatin g 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.  
 
No competing confl icting interests from my side  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I uplo ad will be posted on the website along with the authors'  
responses.  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/ ). I understand that any comments 
which I do  not wish to be included in my named report can be included as confidential comments 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant