Reviewer’s report  
Title: Comparison of the effectiveness of polyethylene glycol with and without electrolytes in  
constipation: a systematic review and network meta -analysis  
 
Version: 0 Date: 06 Nov 2015  
 
Reviewer: Siddharth Singh  
Reviewer’s report:  
In this systematic review and network  meta -analysis, Katelaris and colleagues compared the 
efficacy of PEG vs. PEG with electrolytes based on 19 trials in the management of constipation. 
They observed comparable efficacy, which was higher than placebo or to a variable 'active 
control'.  
 
This is a novel approach of comparative effectiveness of agents. However, there are several 
limitations and assumptions made with this analysis, that merit better discussion:  
 
- The premise of this introducing PEG without electrolytes was to study whether it 
improves taste and compliance. However, this article does not use NMA to address that 
issue of tolerability and safety, but rather just through study reported compliance, etc. Is 
there a way to combine these outcomes into a network design to assess differenc es, 
perhaps using standardized mean differences, or other statistical measures.  
 
- One major assumption of an NMA is that there are minimal differences in patient 
population, co -interventions/background treatment, and outcome measures. I'm unsure 
whether th ese assumptions are met, since there are differences in patient characteristics 
(some functional constipation, others drug -induced, etc), and there is little data on co -
interventions/background treatment. I would recommend adding data if available and 
ackn owledging limitations.  
 
- In a network, it is not correct to lump all 'active controls' together, given different 
inherent response rates. Perhaps a network of all active agents for functional constipation 
would have been more robust and informative.  
 
- How were missing values imputed for continuous outcome - LOCF vs. baseline 
frequency vs. others?  
 
- How was data abstracted from crossover studies?  
 
- Please clarify role of funding sources and two people who were acknowledged, but not 
given authorship. It seems  that at least George Krassas meets general rules of authorship.  
 
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 con trols are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you r ecommend 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 am able to assess the statistics  
 
Quality of written English  
Please in dicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng the following questions:  
 
1. Have you in the past five years received reimbursements, fees, fun ding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, e ither 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 t he publication of this manuscript, e ither 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 fin ancial 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  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on m y report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload 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: Comparison of the effectiveness of polyethylene glycol with and without electrolytes in  
constipation: a systematic review and network meta -analysis  
 
Version: 0 Date: 06 Nov 2015  
 
Reviewer: Siddharth Singh  
Reviewer’s report:  
In this systematic review and network  meta -analysis, Katelaris and colleagues compared the 
efficacy of PEG vs. PEG with electrolytes based on 19 trials in the management of constipation. 
They observed comparable efficacy, which was higher than placebo or to a variable 'active 
control'.  
 
This is a novel approach of comparative effectiveness of agents. However, there are several 
limitations and assumptions made with this analysis, that merit better discussion:  
 
- The premise of this introducing PEG without electrolytes was to study whether it 
improves taste and compliance. However, this article does not use NMA to address that 
issue of tolerability and safety, but rather just through study reported compliance, etc. Is 
there a way to combine these outcomes into a network design to assess differenc es, 
perhaps using standardized mean differences, or other statistical measures.  
 
- One major assumption of an NMA is that there are minimal differences in patient 
population, co -interventions/background treatment, and outcome measures. I'm unsure 
whether th ese assumptions are met, since there are differences in patient characteristics 
(some functional constipation, others drug -induced, etc), and there is little data on co -
interventions/background treatment. I would recommend adding data if available and 
ackn owledging limitations.  
 
- In a network, it is not correct to lump all 'active controls' together, given different 
inherent response rates. Perhaps a network of all active agents for functional constipation 
would have been more robust and informative.  
 
- How were missing values imputed for continuous outcome - LOCF vs. baseline 
frequency vs. others?  
 
- How was data abstracted from crossover studies?  
 
- Please clarify role of funding sources and two people who were acknowledged, but not 
given authorship. It seems  that at least George Krassas meets general rules of authorship.  
 
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 con trols are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you r ecommend 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 am able to assess the statistics  
 
Quality of written English  
Please in dicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng the following questions:  
 
1. Have you in the past five years received reimbursements, fees, fun ding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, e ither 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 t he publication of this manuscript, e ither 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 fin ancial 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  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on m y report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload 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: Comparison of the effectiveness of polyethylene glycol with and without electrolytes in  
constipation: a systematic review and network meta -analysis  
 
Version: 0 Date: 06 Nov 2015  
 
Reviewer: Siddharth Singh  
Reviewer’s report:  
In this systematic review and network  meta -analysis, Katelaris and colleagues compared the 
efficacy of PEG vs. PEG with electrolytes based on 19 trials in the management of constipation. 
They observed comparable efficacy, which was higher than placebo or to a variable 'active 
control'.  
 
This is a novel approach of comparative effectiveness of agents. However, there are several 
limitations and assumptions made with this analysis, that merit better discussion:  
 
- The premise of this introducing PEG without electrolytes was to study whether it 
improves taste and compliance. However, this article does not use NMA to address that 
issue of tolerability and safety, but rather just through study reported compliance, etc. Is 
there a way to combine these outcomes into a network design to assess differenc es, 
perhaps using standardized mean differences, or other statistical measures.  
 
- One major assumption of an NMA is that there are minimal differences in patient 
population, co -interventions/background treatment, and outcome measures. I'm unsure 
whether th ese assumptions are met, since there are differences in patient characteristics 
(some functional constipation, others drug -induced, etc), and there is little data on co -
interventions/background treatment. I would recommend adding data if available and 
ackn owledging limitations.  
 
- In a network, it is not correct to lump all 'active controls' together, given different 
inherent response rates. Perhaps a network of all active agents for functional constipation 
would have been more robust and informative.  
 
- How were missing values imputed for continuous outcome - LOCF vs. baseline 
frequency vs. others?  
 
- How was data abstracted from crossover studies?  
 
- Please clarify role of funding sources and two people who were acknowledged, but not 
given authorship. It seems  that at least George Krassas meets general rules of authorship.  
 
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 con trols are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you r ecommend 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 am able to assess the statistics  
 
Quality of written English  
Please in dicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng the following questions:  
 
1. Have you in the past five years received reimbursements, fees, fun ding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, e ither 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 t he publication of this manuscript, e ither 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 fin ancial 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  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on m y report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload 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