Reviewer ’s report  
 
Title: Novel 1L polyethylene glycol -based bowel preparation (NER1006): proof of concept 
assessment versus standard 2L polyethylene glycol with ascorbate - a randomized parallel group 
Phase 2 colonoscopist -blinded trial  
 
Version: 0 Date:  16 Oct 2018  
 
Reviewer: Ala Sharara  
 
Reviewer's report:  
 
This study report s on the identification of a new lower volume PEG -based preparation and its 
potential use in colonoscopy preparation. The authors use exploratory studies in volunteers to 
select the best purgative with a lower total volume and then test the selected produc ts in a small 
cohort of patients undergoing screening colonoscopy analyzing the quality of the preparation 
compared to the standard 2L PEG with ascorbate. The paper is well done, well written and 
provided most necessary details. Few points, however, need t o be addressed:  
1. No information is provided regarding the diet used by the volunteers in phase 1 or the 
patients in phase 2. A high fiber diet will result in larger stool output in phase 1 whereas a 
low fiber diet is usually a prerequisite for the succe ss of low volume preparations. Was the 
diet standardized for all groups in phase 1 and all patients in phase 2?  
 
2. Were the patients enrolled in phase 2 consecutive patients? It is important to make sure that 
there was no selection bias in phase 2.  
 
3. Although a clear effluent is usually used as a surrogate for an acceptable preparation, studies 
have shown that patients' assessment of the quality of the preparation based on rectal 
effluent is often inaccurate (Fatima H, et al. Gastrointest Endosc 2010; 71 :1244 -52). 
 
4. The near perfect cleansing rates seen with a total of 2L of fluid intake without a stimulant 
laxative is unparalleled and intriguing. These rates are not seen even with split -dose 4 L 
preparations and rarely seen with same day 4L preparations.  
 
5. The H arefield scores in the standard arm are quite inferior to the ones reported with the 
standard preparation. In this study, a grade A was seen in only 20% of patients compared to 
63.4% in the study by Ponchon et al (Dig Liver Dis. 2013;45(10):820 -6.). This d ifference 
raises the question of a possible bias (although the endoscopist was reportedly blinded to the 
group assignment) or that the endoscopist was quite stringent with the scoring.  
 
6. The proof of concept reported in the study is quite interesting. Gi ven the small number of 
patients studied in phase 2, validation in a large randomized controlled trial is required. This 
should involve a larger number of endoscopists with assessment of inter - and intra -observer 
variabilities in the assessment of the bowe l preparation (see point 5 above).  
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.  
 
No 
 
Are the conclusions drawn adequately supported by the data s hown?  
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 aspec ts 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, 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 applied fo r 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 h ave 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 au thors 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: Novel 1L polyethylene glycol -based bowel preparation (NER1006): proof of concept 
assessment versus standard 2L polyethylene glycol with ascorbate - a randomized parallel group 
Phase 2 colonoscopist -blinded trial  
 
Version: 0 Date:  16 Oct 2018  
 
Reviewer: Ala Sharara  
 
Reviewer's report:  
 
This study report s on the identification of a new lower volume PEG -based preparation and its 
potential use in colonoscopy preparation. The authors use exploratory studies in volunteers to 
select the best purgative with a lower total volume and then test the selected produc ts in a small 
cohort of patients undergoing screening colonoscopy analyzing the quality of the preparation 
compared to the standard 2L PEG with ascorbate. The paper is well done, well written and 
provided most necessary details. Few points, however, need t o be addressed:  
1. No information is provided regarding the diet used by the volunteers in phase 1 or the 
patients in phase 2. A high fiber diet will result in larger stool output in phase 1 whereas a 
low fiber diet is usually a prerequisite for the succe ss of low volume preparations. Was the 
diet standardized for all groups in phase 1 and all patients in phase 2?  
 
2. Were the patients enrolled in phase 2 consecutive patients? It is important to make sure that 
there was no selection bias in phase 2.  
 
3. Although a clear effluent is usually used as a surrogate for an acceptable preparation, studies 
have shown that patients' assessment of the quality of the preparation based on rectal 
effluent is often inaccurate (Fatima H, et al. Gastrointest Endosc 2010; 71 :1244 -52). 
 
4. The near perfect cleansing rates seen with a total of 2L of fluid intake without a stimulant 
laxative is unparalleled and intriguing. These rates are not seen even with split -dose 4 L 
preparations and rarely seen with same day 4L preparations.  
 
5. The H arefield scores in the standard arm are quite inferior to the ones reported with the 
standard preparation. In this study, a grade A was seen in only 20% of patients compared to 
63.4% in the study by Ponchon et al (Dig Liver Dis. 2013;45(10):820 -6.). This d ifference 
raises the question of a possible bias (although the endoscopist was reportedly blinded to the 
group assignment) or that the endoscopist was quite stringent with the scoring.  
 
6. The proof of concept reported in the study is quite interesting. Gi ven the small number of 
patients studied in phase 2, validation in a large randomized controlled trial is required. This 
should involve a larger number of endoscopists with assessment of inter - and intra -observer 
variabilities in the assessment of the bowe l preparation (see point 5 above).  
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.  
 
No 
 
Are the conclusions drawn adequately supported by the data s hown?  
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 aspec ts 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, 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 applied fo r 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 h ave 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 au thors 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: Novel 1L polyethylene glycol -based bowel preparation (NER1006): proof of concept 
assessment versus standard 2L polyethylene glycol with ascorbate - a randomized parallel group 
Phase 2 colonoscopist -blinded trial  
 
Version: 0 Date:  16 Oct 2018  
 
Reviewer: Ala Sharara  
 
Reviewer's report:  
 
This study report s on the identification of a new lower volume PEG -based preparation and its 
potential use in colonoscopy preparation. The authors use exploratory studies in volunteers to 
select the best purgative with a lower total volume and then test the selected produc ts in a small 
cohort of patients undergoing screening colonoscopy analyzing the quality of the preparation 
compared to the standard 2L PEG with ascorbate. The paper is well done, well written and 
provided most necessary details. Few points, however, need t o be addressed:  
1. No information is provided regarding the diet used by the volunteers in phase 1 or the 
patients in phase 2. A high fiber diet will result in larger stool output in phase 1 whereas a 
low fiber diet is usually a prerequisite for the succe ss of low volume preparations. Was the 
diet standardized for all groups in phase 1 and all patients in phase 2?  
 
2. Were the patients enrolled in phase 2 consecutive patients? It is important to make sure that 
there was no selection bias in phase 2.  
 
3. Although a clear effluent is usually used as a surrogate for an acceptable preparation, studies 
have shown that patients' assessment of the quality of the preparation based on rectal 
effluent is often inaccurate (Fatima H, et al. Gastrointest Endosc 2010; 71 :1244 -52). 
 
4. The near perfect cleansing rates seen with a total of 2L of fluid intake without a stimulant 
laxative is unparalleled and intriguing. These rates are not seen even with split -dose 4 L 
preparations and rarely seen with same day 4L preparations.  
 
5. The H arefield scores in the standard arm are quite inferior to the ones reported with the 
standard preparation. In this study, a grade A was seen in only 20% of patients compared to 
63.4% in the study by Ponchon et al (Dig Liver Dis. 2013;45(10):820 -6.). This d ifference 
raises the question of a possible bias (although the endoscopist was reportedly blinded to the 
group assignment) or that the endoscopist was quite stringent with the scoring.  
 
6. The proof of concept reported in the study is quite interesting. Gi ven the small number of 
patients studied in phase 2, validation in a large randomized controlled trial is required. This 
should involve a larger number of endoscopists with assessment of inter - and intra -observer 
variabilities in the assessment of the bowe l preparation (see point 5 above).  
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.  
 
No 
 
Are the conclusions drawn adequately supported by the data s hown?  
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 aspec ts 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, 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 applied fo r 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 h ave 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 au thors 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