Reviewer ’s report  
 
Title:  Evaluation of a clinical risk index for advanced colorectal neoplasia among a North 
American population of screening age  
 
Version: 0 Date: 10 Sep 2015  
 
Reviewer: Leo van Rossum  
 
Reviewer’s report:  
 
Dear editor,  
 
The authors have externally validated a previously internally validated risk index for colorectal 
neoplasia. I think this is a well executed study and a thoroughly written manuscript. It not only 
pertains to this particular index, but shows an important step in how indexes like these should be 
validated. Not particularly a landmark paper maybe, but simple enough for readers w ith little 
methodological background to understand what the importance is of this type of research. To my 
opinion, every researcher with a similar dataset should be following in their footsteps.  
 
I have several remarks and suggestions with which I hope the manuscript can become even 
stronger.  
 
First an important remark for reference to the authors: I made the comments in the word 
document with the file name "Kaminski risk index manuscript - BMC Gastro.doc" so not in the 
pdf. I put line numbering per page on i n word, but this probably has resulted in other line 
numbers than in the pdf. Per comment a added if I consider the remark 'minor essential' or 
'discretionary'.  
 
Comments  
 
Title page  
 
Page 1: The title could be stronger as it now only outlines what the author s did not what they 
found: 'Limited utility …' or alternatively 'No clinical utility …' (discretionary)  
 
Similar for the running titel e.g. 'Risk index without clinical utility.' (discretionary)  
 
 
Background  
 
Page 3, line 7: Why do we need to "identifying asym ptomatic persons who might be at an 
increased risk of CRC based " if the recommendation is to screen all? An explanation would 
make the problem analysis stronger. E.g. in the next paragraph the authors write: "…identifying 
individuals who might be recommen ded for screening colonoscopy instead of fecal occult blood 
testing." (minor)  
Page 3, line 12: For the variables that are stated in the previous sentence no FS is needed, so it is 
a bit confusing. (minor)  
 
 
Methods  
 
Page 6, line 16 -17: As clinical utility is the aim of their study, the authors should add to the 
methods that a c -statistic above 0.7 does not yet mean that the index has the desired clinical 
utility. Also it should be stated which parameters are considered for clinical utility. In the 
discussion t he authors could than discuss how the results of these parameters are translated into 
clinical utility if any. (minor)  
 
 
Results  
 
Page 7, line 16: BMI >=30 only added a point for females! A male got 2 points for being male, a 
female got no points for being fe male unless she had a BMI of 30 or higher. This could probably 
be explained better as it might be confusing for readers. (minor)  
 
Page 7, line 20 -22: the authors should consider to make this their last paragraph as clinical utility 
is actually what the auth ors aim for. (discretionary)  
 
Page 8, line 1: This is not a result of the study, because no formal comparison between the two 
studies was made. This statement could be added to the discussion. (minor)  
 
Page 8, line 5 -7: It is not really clear to me what the figure adds to this result? (discretionary)  
 
Page 8, line 8 -9: 'an adenoma' is confusing because the rest of the manuscript only is about 
advanced neoplasia. (minor)  
 
 
Discussion  
 
Page 9 and 10 to line 17: This and the following paragraph could be combined and  shortened, 
which would make it stronger. (minor)  
 
Page 10, line 21: The authors could elaborate on possible additional risk predictors. I  make some 
suggestions. (minor)  
 
- at least the ones they addressed earlier: alcohol, dietary history (red meat consump tion), 
physical activity and FS.  
 
- Family history is known risk factor. Kaminski's index has not put in the Bethesda criteria. 
Could that possibly add substantially to the index?  
 
- The authors could also consider discussing waist circumference instead of  BMI. In several 
publications (broader than the field of colorectal cancer) waist circumference was a better 
predictor than BMI. Waist circumference could probably be quite easily be obtained by adding a 
simple measurement band into the invitation letter, in fact this has been done before (I think in 
breast cancer screening).  
 
Page 11, line 6 -7: can the authors state in a few words what to their opinion would be the next 
validation step for this study. E.g. a similar study as their own? It might encourage re aders with a 
research background to do just that. (discretionary)  
 
Page 12, line 2 -6: these sentences are still part of the discussion, which the authors confirm: 
'strengths and limitations'. (minor)  
 
Page 12, line 3: "We included information on those older than 66 years" is a strength of the study 
compared with the study by Kaminsky. Therefore the authors also analyzed their data without 
the over 66 year olds and it made no difference, which adds strenght to their conclusion that. 
This should be made clearer . (minor)  
 
Is the fact that Kaminsky had a younger age group a significant limitation? It resulted in no 
people with a score of zero. (minor)  
 
Page 12, line 4: The sentence about the age group is a strength, while this sentence about the 
larger proportion of men is a possible limitation. Therefore the word 'Furthermore' is somewhat 
confusing. (discretionary)  
 
 
Conclusion  
 
Page 12, line 9 -10: Can the  authors explain what the clinical utility is if any? In the abstract they 
state: "…may be useful for prioritizing screening with colonoscopy." So what do they conclude, 
is it in any way useful fort hat purpose? (minor)  
 
 
Figure  
 
Page 25, figure 1: The title is not complete. In the graph a distinction is made between the age 
group to 66 and the overall cohort. (minor)  
 
Page 25, figure 1: Also the authors should consider to make a legend to explain that there weren't 
any people with a score of zero or thye might  simply add a zero score with a proportion of zero 
to the graph. Probably the latter is the easiest and clearest for the readers. (minor)  
 
Are the methods appropriate and well desc ribed?  
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 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 rec ommended, 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 indicate the quality 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 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, 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 relatin g 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 int erests' 
below. If your reply is yes to any, please give details below.  
 
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 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:  Evaluation of a clinical risk index for advanced colorectal neoplasia among a North 
American population of screening age  
 
Version: 0 Date: 10 Sep 2015  
 
Reviewer: Leo van Rossum  
 
Reviewer’s report:  
 
Dear editor,  
 
The authors have externally validated a previously internally validated risk index for colorectal 
neoplasia. I think this is a well executed study and a thoroughly written manuscript. It not only 
pertains to this particular index, but shows an important step in how indexes like these should be 
validated. Not particularly a landmark paper maybe, but simple enough for readers w ith little 
methodological background to understand what the importance is of this type of research. To my 
opinion, every researcher with a similar dataset should be following in their footsteps.  
 
I have several remarks and suggestions with which I hope the manuscript can become even 
stronger.  
 
First an important remark for reference to the authors: I made the comments in the word 
document with the file name "Kaminski risk index manuscript - BMC Gastro.doc" so not in the 
pdf. I put line numbering per page on i n word, but this probably has resulted in other line 
numbers than in the pdf. Per comment a added if I consider the remark 'minor essential' or 
'discretionary'.  
 
Comments  
 
Title page  
 
Page 1: The title could be stronger as it now only outlines what the author s did not what they 
found: 'Limited utility …' or alternatively 'No clinical utility …' (discretionary)  
 
Similar for the running titel e.g. 'Risk index without clinical utility.' (discretionary)  
 
 
Background  
 
Page 3, line 7: Why do we need to "identifying asym ptomatic persons who might be at an 
increased risk of CRC based " if the recommendation is to screen all? An explanation would 
make the problem analysis stronger. E.g. in the next paragraph the authors write: "…identifying 
individuals who might be recommen ded for screening colonoscopy instead of fecal occult blood 
testing." (minor)  
Page 3, line 12: For the variables that are stated in the previous sentence no FS is needed, so it is 
a bit confusing. (minor)  
 
 
Methods  
 
Page 6, line 16 -17: As clinical utility is the aim of their study, the authors should add to the 
methods that a c -statistic above 0.7 does not yet mean that the index has the desired clinical 
utility. Also it should be stated which parameters are considered for clinical utility. In the 
discussion t he authors could than discuss how the results of these parameters are translated into 
clinical utility if any. (minor)  
 
 
Results  
 
Page 7, line 16: BMI >=30 only added a point for females! A male got 2 points for being male, a 
female got no points for being fe male unless she had a BMI of 30 or higher. This could probably 
be explained better as it might be confusing for readers. (minor)  
 
Page 7, line 20 -22: the authors should consider to make this their last paragraph as clinical utility 
is actually what the auth ors aim for. (discretionary)  
 
Page 8, line 1: This is not a result of the study, because no formal comparison between the two 
studies was made. This statement could be added to the discussion. (minor)  
 
Page 8, line 5 -7: It is not really clear to me what the figure adds to this result? (discretionary)  
 
Page 8, line 8 -9: 'an adenoma' is confusing because the rest of the manuscript only is about 
advanced neoplasia. (minor)  
 
 
Discussion  
 
Page 9 and 10 to line 17: This and the following paragraph could be combined and  shortened, 
which would make it stronger. (minor)  
 
Page 10, line 21: The authors could elaborate on possible additional risk predictors. I  make some 
suggestions. (minor)  
 
- at least the ones they addressed earlier: alcohol, dietary history (red meat consump tion), 
physical activity and FS.  
 
- Family history is known risk factor. Kaminski's index has not put in the Bethesda criteria. 
Could that possibly add substantially to the index?  
 
- The authors could also consider discussing waist circumference instead of  BMI. In several 
publications (broader than the field of colorectal cancer) waist circumference was a better 
predictor than BMI. Waist circumference could probably be quite easily be obtained by adding a 
simple measurement band into the invitation letter, in fact this has been done before (I think in 
breast cancer screening).  
 
Page 11, line 6 -7: can the authors state in a few words what to their opinion would be the next 
validation step for this study. E.g. a similar study as their own? It might encourage re aders with a 
research background to do just that. (discretionary)  
 
Page 12, line 2 -6: these sentences are still part of the discussion, which the authors confirm: 
'strengths and limitations'. (minor)  
 
Page 12, line 3: "We included information on those older than 66 years" is a strength of the study 
compared with the study by Kaminsky. Therefore the authors also analyzed their data without 
the over 66 year olds and it made no difference, which adds strenght to their conclusion that. 
This should be made clearer . (minor)  
 
Is the fact that Kaminsky had a younger age group a significant limitation? It resulted in no 
people with a score of zero. (minor)  
 
Page 12, line 4: The sentence about the age group is a strength, while this sentence about the 
larger proportion of men is a possible limitation. Therefore the word 'Furthermore' is somewhat 
confusing. (discretionary)  
 
 
Conclusion  
 
Page 12, line 9 -10: Can the  authors explain what the clinical utility is if any? In the abstract they 
state: "…may be useful for prioritizing screening with colonoscopy." So what do they conclude, 
is it in any way useful fort hat purpose? (minor)  
 
 
Figure  
 
Page 25, figure 1: The title is not complete. In the graph a distinction is made between the age 
group to 66 and the overall cohort. (minor)  
 
Page 25, figure 1: Also the authors should consider to make a legend to explain that there weren't 
any people with a score of zero or thye might  simply add a zero score with a proportion of zero 
to the graph. Probably the latter is the easiest and clearest for the readers. (minor)  
 
Are the methods appropriate and well desc ribed?  
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 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 rec ommended, 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 indicate the quality 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 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, 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 relatin g 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 int erests' 
below. If your reply is yes to any, please give details below.  
 
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 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:  Evaluation of a clinical risk index for advanced colorectal neoplasia among a North 
American population of screening age  
 
Version: 0 Date: 10 Sep 2015  
 
Reviewer: Leo van Rossum  
 
Reviewer’s report:  
 
Dear editor,  
 
The authors have externally validated a previously internally validated risk index for colorectal 
neoplasia. I think this is a well executed study and a thoroughly written manuscript. It not only 
pertains to this particular index, but shows an important step in how indexes like these should be 
validated. Not particularly a landmark paper maybe, but simple enough for readers w ith little 
methodological background to understand what the importance is of this type of research. To my 
opinion, every researcher with a similar dataset should be following in their footsteps.  
 
I have several remarks and suggestions with which I hope the manuscript can become even 
stronger.  
 
First an important remark for reference to the authors: I made the comments in the word 
document with the file name "Kaminski risk index manuscript - BMC Gastro.doc" so not in the 
pdf. I put line numbering per page on i n word, but this probably has resulted in other line 
numbers than in the pdf. Per comment a added if I consider the remark 'minor essential' or 
'discretionary'.  
 
Comments  
 
Title page  
 
Page 1: The title could be stronger as it now only outlines what the author s did not what they 
found: 'Limited utility …' or alternatively 'No clinical utility …' (discretionary)  
 
Similar for the running titel e.g. 'Risk index without clinical utility.' (discretionary)  
 
 
Background  
 
Page 3, line 7: Why do we need to "identifying asym ptomatic persons who might be at an 
increased risk of CRC based " if the recommendation is to screen all? An explanation would 
make the problem analysis stronger. E.g. in the next paragraph the authors write: "…identifying 
individuals who might be recommen ded for screening colonoscopy instead of fecal occult blood 
testing." (minor)  
Page 3, line 12: For the variables that are stated in the previous sentence no FS is needed, so it is 
a bit confusing. (minor)  
 
 
Methods  
 
Page 6, line 16 -17: As clinical utility is the aim of their study, the authors should add to the 
methods that a c -statistic above 0.7 does not yet mean that the index has the desired clinical 
utility. Also it should be stated which parameters are considered for clinical utility. In the 
discussion t he authors could than discuss how the results of these parameters are translated into 
clinical utility if any. (minor)  
 
 
Results  
 
Page 7, line 16: BMI >=30 only added a point for females! A male got 2 points for being male, a 
female got no points for being fe male unless she had a BMI of 30 or higher. This could probably 
be explained better as it might be confusing for readers. (minor)  
 
Page 7, line 20 -22: the authors should consider to make this their last paragraph as clinical utility 
is actually what the auth ors aim for. (discretionary)  
 
Page 8, line 1: This is not a result of the study, because no formal comparison between the two 
studies was made. This statement could be added to the discussion. (minor)  
 
Page 8, line 5 -7: It is not really clear to me what the figure adds to this result? (discretionary)  
 
Page 8, line 8 -9: 'an adenoma' is confusing because the rest of the manuscript only is about 
advanced neoplasia. (minor)  
 
 
Discussion  
 
Page 9 and 10 to line 17: This and the following paragraph could be combined and  shortened, 
which would make it stronger. (minor)  
 
Page 10, line 21: The authors could elaborate on possible additional risk predictors. I  make some 
suggestions. (minor)  
 
- at least the ones they addressed earlier: alcohol, dietary history (red meat consump tion), 
physical activity and FS.  
 
- Family history is known risk factor. Kaminski's index has not put in the Bethesda criteria. 
Could that possibly add substantially to the index?  
 
- The authors could also consider discussing waist circumference instead of  BMI. In several 
publications (broader than the field of colorectal cancer) waist circumference was a better 
predictor than BMI. Waist circumference could probably be quite easily be obtained by adding a 
simple measurement band into the invitation letter, in fact this has been done before (I think in 
breast cancer screening).  
 
Page 11, line 6 -7: can the authors state in a few words what to their opinion would be the next 
validation step for this study. E.g. a similar study as their own? It might encourage re aders with a 
research background to do just that. (discretionary)  
 
Page 12, line 2 -6: these sentences are still part of the discussion, which the authors confirm: 
'strengths and limitations'. (minor)  
 
Page 12, line 3: "We included information on those older than 66 years" is a strength of the study 
compared with the study by Kaminsky. Therefore the authors also analyzed their data without 
the over 66 year olds and it made no difference, which adds strenght to their conclusion that. 
This should be made clearer . (minor)  
 
Is the fact that Kaminsky had a younger age group a significant limitation? It resulted in no 
people with a score of zero. (minor)  
 
Page 12, line 4: The sentence about the age group is a strength, while this sentence about the 
larger proportion of men is a possible limitation. Therefore the word 'Furthermore' is somewhat 
confusing. (discretionary)  
 
 
Conclusion  
 
Page 12, line 9 -10: Can the  authors explain what the clinical utility is if any? In the abstract they 
state: "…may be useful for prioritizing screening with colonoscopy." So what do they conclude, 
is it in any way useful fort hat purpose? (minor)  
 
 
Figure  
 
Page 25, figure 1: The title is not complete. In the graph a distinction is made between the age 
group to 66 and the overall cohort. (minor)  
 
Page 25, figure 1: Also the authors should consider to make a legend to explain that there weren't 
any people with a score of zero or thye might  simply add a zero score with a proportion of zero 
to the graph. Probably the latter is the easiest and clearest for the readers. (minor)  
 
Are the methods appropriate and well desc ribed?  
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 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 rec ommended, 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 indicate the quality 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 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, 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 relatin g 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 int erests' 
below. If your reply is yes to any, please give details below.  
 
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 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