Reviewer ’s report  
 
Title: Economic burden of moderate to severe Irritable Bowel Syndrome with Constipation in 
six European countries  
 
Version: 0 Date: 21 Feb 2019  
 
Reviewer: Mich ael Camilleri  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to the authors.  
 
This is an interesting multi -national study assessing healthcare costs in several European 
countries.  The data are well documented in the manuscript and tables.  The following comments 
are intended to strengthen the manuscript and acknowledge additional limitations  
 
1. Biased sample: Study center recruitment in table 1 shows that most p atients were attending 
specialist centers and only Germany and Spain had recruited participants from primary care.  
Therefore, this introduces referral bias in the sample studied. This needs to be acknowledged in 
the discussion.  
 
2. Comparison between healt h care utilization and costs between specialist care and primary care 
patients: though the sample size is small, it may be worth contrasting the results with the 
specialist care cohort in the SAME countries, that is Germany and Spain  
 
3. You need to discuss  the potential limitation introduced by the fact that the sample size 
required 90 per country and this was not achieved by several participating countries e.g. Sweden 
and France.  
 
4. Given the small sample size in Sweden, and the specialty care cohort there , it may be that the 
indirect costs in Sweden need to be downplayed as they may be reflective of the same secondary 
or tertiary care bias which may be more accessible to higher paid patients.  This may be totally 
wrong....and if so, you need to discuss it.  
 
5. Some of the health care costs reflect utilization of tests.  Do you have information on the types 
of test e.g. relatively expensive colonoscopy or CT imaging?  If possible, how might these costs 
be reduced e.g. with biomarkers, such as stool DNA marker s or blood to screen for colon cancer; 
with colonic transit and anorectal manometry to obtain more specific diagnosis than the 
exclusive symptom -based criteria for IBS -C, which do not define whether to treat rectal 
evacuation disorder or introduce more eff ective therapy earlier, and avoid emergency department 
attendance or even hospitalization.  
 
6. With regard to hospitalization, there is an opportunity to discuss the results of health care 
utilization for GI indications from the work of Peery A, Sandler R e t al at University of North 
Carolina in USA.   Those studies also show significant health care utilization and hospitalization 
costs due to constipation.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your co mments 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 comments to the authors.  
 
Yes 
 
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 req uire 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 declarat ion 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 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 pat ents 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  
 
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 atta chments 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: Economic burden of moderate to severe Irritable Bowel Syndrome with Constipation in 
six European countries  
 
Version: 0 Date: 21 Feb 2019  
 
Reviewer: Mich ael Camilleri  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to the authors.  
 
This is an interesting multi -national study assessing healthcare costs in several European 
countries.  The data are well documented in the manuscript and tables.  The following comments 
are intended to strengthen the manuscript and acknowledge additional limitations  
 
1. Biased sample: Study center recruitment in table 1 shows that most p atients were attending 
specialist centers and only Germany and Spain had recruited participants from primary care.  
Therefore, this introduces referral bias in the sample studied. This needs to be acknowledged in 
the discussion.  
 
2. Comparison between healt h care utilization and costs between specialist care and primary care 
patients: though the sample size is small, it may be worth contrasting the results with the 
specialist care cohort in the SAME countries, that is Germany and Spain  
 
3. You need to discuss  the potential limitation introduced by the fact that the sample size 
required 90 per country and this was not achieved by several participating countries e.g. Sweden 
and France.  
 
4. Given the small sample size in Sweden, and the specialty care cohort there , it may be that the 
indirect costs in Sweden need to be downplayed as they may be reflective of the same secondary 
or tertiary care bias which may be more accessible to higher paid patients.  This may be totally 
wrong....and if so, you need to discuss it.  
 
5. Some of the health care costs reflect utilization of tests.  Do you have information on the types 
of test e.g. relatively expensive colonoscopy or CT imaging?  If possible, how might these costs 
be reduced e.g. with biomarkers, such as stool DNA marker s or blood to screen for colon cancer; 
with colonic transit and anorectal manometry to obtain more specific diagnosis than the 
exclusive symptom -based criteria for IBS -C, which do not define whether to treat rectal 
evacuation disorder or introduce more eff ective therapy earlier, and avoid emergency department 
attendance or even hospitalization.  
 
6. With regard to hospitalization, there is an opportunity to discuss the results of health care 
utilization for GI indications from the work of Peery A, Sandler R e t al at University of North 
Carolina in USA.   Those studies also show significant health care utilization and hospitalization 
costs due to constipation.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your co mments 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 comments to the authors.  
 
Yes 
 
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 req uire 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 declarat ion 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 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 pat ents 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  
 
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 atta chments 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: Economic burden of moderate to severe Irritable Bowel Syndrome with Constipation in 
six European countries  
 
Version: 0 Date: 21 Feb 2019  
 
Reviewer: Mich ael Camilleri  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to the authors.  
 
This is an interesting multi -national study assessing healthcare costs in several European 
countries.  The data are well documented in the manuscript and tables.  The following comments 
are intended to strengthen the manuscript and acknowledge additional limitations  
 
1. Biased sample: Study center recruitment in table 1 shows that most p atients were attending 
specialist centers and only Germany and Spain had recruited participants from primary care.  
Therefore, this introduces referral bias in the sample studied. This needs to be acknowledged in 
the discussion.  
 
2. Comparison between healt h care utilization and costs between specialist care and primary care 
patients: though the sample size is small, it may be worth contrasting the results with the 
specialist care cohort in the SAME countries, that is Germany and Spain  
 
3. You need to discuss  the potential limitation introduced by the fact that the sample size 
required 90 per country and this was not achieved by several participating countries e.g. Sweden 
and France.  
 
4. Given the small sample size in Sweden, and the specialty care cohort there , it may be that the 
indirect costs in Sweden need to be downplayed as they may be reflective of the same secondary 
or tertiary care bias which may be more accessible to higher paid patients.  This may be totally 
wrong....and if so, you need to discuss it.  
 
5. Some of the health care costs reflect utilization of tests.  Do you have information on the types 
of test e.g. relatively expensive colonoscopy or CT imaging?  If possible, how might these costs 
be reduced e.g. with biomarkers, such as stool DNA marker s or blood to screen for colon cancer; 
with colonic transit and anorectal manometry to obtain more specific diagnosis than the 
exclusive symptom -based criteria for IBS -C, which do not define whether to treat rectal 
evacuation disorder or introduce more eff ective therapy earlier, and avoid emergency department 
attendance or even hospitalization.  
 
6. With regard to hospitalization, there is an opportunity to discuss the results of health care 
utilization for GI indications from the work of Peery A, Sandler R e t al at University of North 
Carolina in USA.   Those studies also show significant health care utilization and hospitalization 
costs due to constipation.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your co mments 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 comments to the authors.  
 
Yes 
 
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 req uire 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 declarat ion 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 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 pat ents 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  
 
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 atta chments 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