Reviewer ’s report  
 
Title: Pre-endoscopy Point of Care Test (Simtomax - IgA/IgG -Deamidated Gliadin Peptide) for  
Coeliac Disease in Iron Deficiency Anaemia: Diagnostic Accu racy and a Cost Saving Economic  
Model  
 
Version: 0 Date: 25 May 2016  
 
Reviewer: Paul Kelly  
 
Reviewer's report:  
 
This is a well -written and thorough investigation of an important question. The authors show that 
Simtomax testing, compared to well -characte rised gold standard diagnosis of coeliac disease, is 
very accurate and, most importantly, has a very high negative predictive value. I have two major 
criticisms of the manuscript as submitted:  
 
 
 
1. The authors claim, in Discussion, p14 line 16, in the paragr aph beginning "Our duodenal 
histology..." that duodenal biopsy makes no important diagnoses in Simtomax -negative 
patients. This is true in the third group, but in their second group one of their seronegative 
patients turned out to have duodenal TB, which i s rare but undermines their claim that 
omitting duodenal biopsy in seronegative patients would miss nothing important. If I 
were a patient I would not be reassured that a duodenal biopsy was felt to be unimportant 
on the ba sis of a good serological test.  
 
 
 
2. The economic analysis is also very slightly misleading in that it supposes that the NHS 
could save a substantial amount of money by not doing duodenal histology. While 
superficially attractive, this supposes that the histopathology department could lay off or 
dismiss staff if such tests were not done. In fact, the staff will be working irrespective of 
the small extra workload of these biopsies, and I find this argument unconvincing.  
 
I would be happy if the authors could qualify these two statements in t he Discussion.  
 
 
 
Minor points:  
 
3. The prevalence of coeliac disease is 1% when measured serologically; it is contentious 
that this reflects the true prevalence of the full -blown disease which is really only 
diagnosed histologically.  
 
 
4. The authors are vague a bout which other hospital was used for the 3rd group. This should 
be specified.  
 
 
5. Is it standard practice in these hospitals to orientate the biopsy prior to fixation, in order 
to achieve more accurate assessment of villus architecture?  
 
 
 
Are the methods approp riate 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 comments 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 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 wa y 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 t he 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 cont ent 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 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 attachments I uploa d will be posted on the website along 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 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: Pre-endoscopy Point of Care Test (Simtomax - IgA/IgG -Deamidated Gliadin Peptide) for  
Coeliac Disease in Iron Deficiency Anaemia: Diagnostic Accu racy and a Cost Saving Economic  
Model  
 
Version: 0 Date: 25 May 2016  
 
Reviewer: Paul Kelly  
 
Reviewer's report:  
 
This is a well -written and thorough investigation of an important question. The authors show that 
Simtomax testing, compared to well -characte rised gold standard diagnosis of coeliac disease, is 
very accurate and, most importantly, has a very high negative predictive value. I have two major 
criticisms of the manuscript as submitted:  
 
 
 
1. The authors claim, in Discussion, p14 line 16, in the paragr aph beginning "Our duodenal 
histology..." that duodenal biopsy makes no important diagnoses in Simtomax -negative 
patients. This is true in the third group, but in their second group one of their seronegative 
patients turned out to have duodenal TB, which i s rare but undermines their claim that 
omitting duodenal biopsy in seronegative patients would miss nothing important. If I 
were a patient I would not be reassured that a duodenal biopsy was felt to be unimportant 
on the ba sis of a good serological test.  
 
 
 
2. The economic analysis is also very slightly misleading in that it supposes that the NHS 
could save a substantial amount of money by not doing duodenal histology. While 
superficially attractive, this supposes that the histopathology department could lay off or 
dismiss staff if such tests were not done. In fact, the staff will be working irrespective of 
the small extra workload of these biopsies, and I find this argument unconvincing.  
 
I would be happy if the authors could qualify these two statements in t he Discussion.  
 
 
 
Minor points:  
 
3. The prevalence of coeliac disease is 1% when measured serologically; it is contentious 
that this reflects the true prevalence of the full -blown disease which is really only 
diagnosed histologically.  
 
 
4. The authors are vague a bout which other hospital was used for the 3rd group. This should 
be specified.  
 
 
5. Is it standard practice in these hospitals to orientate the biopsy prior to fixation, in order 
to achieve more accurate assessment of villus architecture?  
 
 
 
Are the methods approp riate 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 comments 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 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 wa y 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 t he 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 cont ent 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 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 attachments I uploa d will be posted on the website along 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 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: Pre-endoscopy Point of Care Test (Simtomax - IgA/IgG -Deamidated Gliadin Peptide) for  
Coeliac Disease in Iron Deficiency Anaemia: Diagnostic Accu racy and a Cost Saving Economic  
Model  
 
Version: 0 Date: 25 May 2016  
 
Reviewer: Paul Kelly  
 
Reviewer's report:  
 
This is a well -written and thorough investigation of an important question. The authors show that 
Simtomax testing, compared to well -characte rised gold standard diagnosis of coeliac disease, is 
very accurate and, most importantly, has a very high negative predictive value. I have two major 
criticisms of the manuscript as submitted:  
 
 
 
1. The authors claim, in Discussion, p14 line 16, in the paragr aph beginning "Our duodenal 
histology..." that duodenal biopsy makes no important diagnoses in Simtomax -negative 
patients. This is true in the third group, but in their second group one of their seronegative 
patients turned out to have duodenal TB, which i s rare but undermines their claim that 
omitting duodenal biopsy in seronegative patients would miss nothing important. If I 
were a patient I would not be reassured that a duodenal biopsy was felt to be unimportant 
on the ba sis of a good serological test.  
 
 
 
2. The economic analysis is also very slightly misleading in that it supposes that the NHS 
could save a substantial amount of money by not doing duodenal histology. While 
superficially attractive, this supposes that the histopathology department could lay off or 
dismiss staff if such tests were not done. In fact, the staff will be working irrespective of 
the small extra workload of these biopsies, and I find this argument unconvincing.  
 
I would be happy if the authors could qualify these two statements in t he Discussion.  
 
 
 
Minor points:  
 
3. The prevalence of coeliac disease is 1% when measured serologically; it is contentious 
that this reflects the true prevalence of the full -blown disease which is really only 
diagnosed histologically.  
 
 
4. The authors are vague a bout which other hospital was used for the 3rd group. This should 
be specified.  
 
 
5. Is it standard practice in these hospitals to orientate the biopsy prior to fixation, in order 
to achieve more accurate assessment of villus architecture?  
 
 
 
Are the methods approp riate 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 comments 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 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 wa y 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 t he 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 cont ent 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 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 attachments I uploa d will be posted on the website along 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 included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant