Reviewer ’s report  
 
Title: Indirect costs associated with Ulcerative colitis: a systematic literature review of real -
world data 
 
Version: 0 Date: 21 Jul 2019  
 
Reviewer: Johan Burisch  
 
Reviewer's report:  
 
Constantin and colleagues report findings from a systematic review of the indirect costs of 
ulcerative colitis (UC). The authors included observational studies investigating indirect costs or 
productivity l osses associated with absenteeism and/or presenteeism in patients with 
moderate/severe active UC. A total of 18 studies met inclusion criteria and were included in the 
study.  
 
Indirect costs in UC patients were difficult to asses due to variation between t he studies and the 
low number of studies addressing each outcome of interest. However, this is an important and 
relevant topic with limited available evidence available.  
 
 
I have the following comments:  
 
- I would suggest changing the title so that it is cl ear to the reader that the review only 
addresses indirect but not direct costs.  
 
- The search strategy did not include "absenteeism". Would this have changed the outcome 
of the search?  
 
- Why did the authors choose only to include studies of patients with a ctive disease? It 
seems a missed opportunity to deliver a complete picture if the author excluded studies 
covering also mild patients or patients in remission.  
 
- Please explain the differences regarding the number of included studies compared to the 
recen t reviews by Kawalec and colleagues.  
 
- There are some errors in the reference list as well as in the references within the main 
text.  
 
- None of the studies are population -based, which should be mentioned as one of the 
limitations. Findings are therefore more likely to be biased and not representative of the 
total UC population. Also, did theses studies compare patients with controls?  
 
- A recent study (Lo et all, Journal of Crohn's &amp;  Colitis 2019) published after the 
literature search addresses indirec t and direct costs in IBD and should be discussed.  
- An important message of this study is the fact that available studies are few, include 
selected patients and are heterogeneous. I would suggest also emphasizing this more in 
the discussion, as studies on  indirect costs are important in a time where direct costs are 
increasing substantially.  
 
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.  
 
Unable to assess  
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the qualit y of language in the manuscript:  
 
Acceptable  
 
Declaration 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 financial ly from the 
publication of this manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 ap plied 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website a long with the authors' 
responses. I agree for my report to be made available under an Open Acc ess 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 in cluded 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: Indirect costs associated with Ulcerative colitis: a systematic literature review of real -
world data 
 
Version: 0 Date: 21 Jul 2019  
 
Reviewer: Johan Burisch  
 
Reviewer's report:  
 
Constantin and colleagues report findings from a systematic review of the indirect costs of 
ulcerative colitis (UC). The authors included observational studies investigating indirect costs or 
productivity l osses associated with absenteeism and/or presenteeism in patients with 
moderate/severe active UC. A total of 18 studies met inclusion criteria and were included in the 
study.  
 
Indirect costs in UC patients were difficult to asses due to variation between t he studies and the 
low number of studies addressing each outcome of interest. However, this is an important and 
relevant topic with limited available evidence available.  
 
 
I have the following comments:  
 
- I would suggest changing the title so that it is cl ear to the reader that the review only 
addresses indirect but not direct costs.  
 
- The search strategy did not include "absenteeism". Would this have changed the outcome 
of the search?  
 
- Why did the authors choose only to include studies of patients with a ctive disease? It 
seems a missed opportunity to deliver a complete picture if the author excluded studies 
covering also mild patients or patients in remission.  
 
- Please explain the differences regarding the number of included studies compared to the 
recen t reviews by Kawalec and colleagues.  
 
- There are some errors in the reference list as well as in the references within the main 
text.  
 
- None of the studies are population -based, which should be mentioned as one of the 
limitations. Findings are therefore more likely to be biased and not representative of the 
total UC population. Also, did theses studies compare patients with controls?  
 
- A recent study (Lo et all, Journal of Crohn's &amp;  Colitis 2019) published after the 
literature search addresses indirec t and direct costs in IBD and should be discussed.  
- An important message of this study is the fact that available studies are few, include 
selected patients and are heterogeneous. I would suggest also emphasizing this more in 
the discussion, as studies on  indirect costs are important in a time where direct costs are 
increasing substantially.  
 
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.  
 
Unable to assess  
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the qualit y of language in the manuscript:  
 
Acceptable  
 
Declaration 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 financial ly from the 
publication of this manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 ap plied 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website a long with the authors' 
responses. I agree for my report to be made available under an Open Acc ess 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 in cluded 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: Indirect costs associated with Ulcerative colitis: a systematic literature review of real -
world data 
 
Version: 0 Date: 21 Jul 2019  
 
Reviewer: Johan Burisch  
 
Reviewer's report:  
 
Constantin and colleagues report findings from a systematic review of the indirect costs of 
ulcerative colitis (UC). The authors included observational studies investigating indirect costs or 
productivity l osses associated with absenteeism and/or presenteeism in patients with 
moderate/severe active UC. A total of 18 studies met inclusion criteria and were included in the 
study.  
 
Indirect costs in UC patients were difficult to asses due to variation between t he studies and the 
low number of studies addressing each outcome of interest. However, this is an important and 
relevant topic with limited available evidence available.  
 
 
I have the following comments:  
 
- I would suggest changing the title so that it is cl ear to the reader that the review only 
addresses indirect but not direct costs.  
 
- The search strategy did not include "absenteeism". Would this have changed the outcome 
of the search?  
 
- Why did the authors choose only to include studies of patients with a ctive disease? It 
seems a missed opportunity to deliver a complete picture if the author excluded studies 
covering also mild patients or patients in remission.  
 
- Please explain the differences regarding the number of included studies compared to the 
recen t reviews by Kawalec and colleagues.  
 
- There are some errors in the reference list as well as in the references within the main 
text.  
 
- None of the studies are population -based, which should be mentioned as one of the 
limitations. Findings are therefore more likely to be biased and not representative of the 
total UC population. Also, did theses studies compare patients with controls?  
 
- A recent study (Lo et all, Journal of Crohn's &amp;  Colitis 2019) published after the 
literature search addresses indirec t and direct costs in IBD and should be discussed.  
- An important message of this study is the fact that available studies are few, include 
selected patients and are heterogeneous. I would suggest also emphasizing this more in 
the discussion, as studies on  indirect costs are important in a time where direct costs are 
increasing substantially.  
 
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.  
 
Unable to assess  
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the qualit y of language in the manuscript:  
 
Acceptable  
 
Declaration 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 financial ly from the 
publication of this manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 ap plied 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website a long with the authors' 
responses. I agree for my report to be made available under an Open Acc ess 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 in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant