Title: 1L NER1006 can improve rates of adequate and high-quality bowel cleansing in the right
colon: a post hoc analysis of two randomised clinical trials
Version: 0 Date: 26 Oct 2021
Reviewer's report:
This post hoc analysis from two previous studies (MORA, NOCT) included 1,307 patients,
aimed to evaluate the 4 following topics;
- Whether those three regimens; NER1006, 2LPEG, and OSS can attain an adequate cleansing
level in the right colon greater than 90% using the Harefield Cleansing Scale.
- Comparative adequate and high-quality cleansing levels were attained in the right colon with
NER1006 and comparators
- Comparative adequate-quality cleansing level attained by NER1006 in the right colon and all
other colon segments
- The cleansing impact of NER1006 in the right colon in patients who are at increased risk for
inadequate bowel preparation
The cleansing performance in this post hoc analysis was evaluated via recorded VDO by central
readers.
Although the topics in this study are interesting in themselves and deserve a constructive
discussion, I have a few comments as indicated below. I hope these comments will be helpful.
Comments
1. The title of the study can be confused the readers. The total volume of the preparation regimen
was 2 liters and the design of the retrospective study was not mentioned.
2. The mFAS2 population set used in this analysis did not represent the real-world situation as
some of the randomized patients did not take the study drug, for unknown reasons. And the main
limitation of participants in this study was selective using only patients who had been assessed
for Harefield Cleansing Scale in all segments.
3. The fasting time before colonoscopy in these cohorts was very short, only 1-2 hours. I think
this protocol was the most important contribution to the excellent preparation quality in the right
side colon and also the whole colon. This issue should be emphasized to the readers.
4. How many VDO readers that involved in the data collection. How was the agreement among
the readers? Were readers blinded for the bowel preparation regimens?
5. Figure 2a showed the percentage of adequate preparation in the right colon segment and the p-
value demonstrated the difference between each regimen and minimum standard recommended
by ESGE. I think it was not necessary to demonstrate.
6. Authors mentioned in the background that the right-sided colon was the most difficult segment
to prep. What is the reason to compare the right colon prep with other segments? The comparison
among each segment preparation quality and 90%target did not add any value to the readers. I
suggest shortening the result of the study and all figure 4 (a-d) should be removed.
7. In supplementary table 3, the mean BMI of all cohorts was over 25 kg/m2. The authors should
demonstrate the percentage of overweight patients (BMI # 25 kg/m2) in table 3. This will enable
the reader to understand the overall characteristic of hard-to-cleanse patients.
8. The hard-to-cleanse patients in this study defined only male patients with BMI # 25 kg/m2.
However, the predictive factors for difficult preparation also included the elderly, in-patient
status for colonoscopy, patients with constipation, or patients with comorbidities. What were the
reasons for not including other important factors contributing to hard- or difficult-to-cleanse? If
so, the authors should replace hard-to-cleanse patients to overweight patients.
9. Figure 5a, 5b can be combined, and figure 5c and 5d can be combined. Or for minimizing
confusion, figure 5d can be omitted.
10. It seems that the discussion was the repeated writing of the result. Please provide a discussion
on the reasons for your findings. Why the right-sided colon was well cleaned with NER1006
than other regimens.
11. If the MORA and NOCT participants were almost identical, I suggest incorporating two
N2D NER1006 cohorts and analyzing them as a single cohort. This will reduce the difficulty
to read and follow this study.
Title: 1L NER1006 can improve rates of adequate and high-quality bowel cleansing in the right
colon: a post hoc analysis of two randomised clinical trials
Version: 0 Date: 26 Oct 2021
Reviewer's report:
This post hoc analysis from two previous studies (MORA, NOCT) included 1,307 patients,
aimed to evaluate the 4 following topics;
- Whether those three regimens; NER1006, 2LPEG, and OSS can attain an adequate cleansing
level in the right colon greater than 90% using the Harefield Cleansing Scale.
- Comparative adequate and high-quality cleansing levels were attained in the right colon with
NER1006 and comparators
- Comparative adequate-quality cleansing level attained by NER1006 in the right colon and all
other colon segments
- The cleansing impact of NER1006 in the right colon in patients who are at increased risk for
inadequate bowel preparation
The cleansing performance in this post hoc analysis was evaluated via recorded VDO by central
readers.
Although the topics in this study are interesting in themselves and deserve a constructive
discussion, I have a few comments as indicated below. I hope these comments will be helpful.
Comments
1. The title of the study can be confused the readers. The total volume of the preparation regimen
was 2 liters and the design of the retrospective study was not mentioned.
2. The mFAS2 population set used in this analysis did not represent the real-world situation as
some of the randomized patients did not take the study drug, for unknown reasons. And the main
limitation of participants in this study was selective using only patients who had been assessed
for Harefield Cleansing Scale in all segments.
3. The fasting time before colonoscopy in these cohorts was very short, only 1-2 hours. I think
this protocol was the most important contribution to the excellent preparation quality in the right
side colon and also the whole colon. This issue should be emphasized to the readers.
4. How many VDO readers that involved in the data collection. How was the agreement among
the readers? Were readers blinded for the bowel preparation regimens?
5. Figure 2a showed the percentage of adequate preparation in the right colon segment and the p-
value demonstrated the difference between each regimen and minimum standard recommended
by ESGE. I think it was not necessary to demonstrate.
6. Authors mentioned in the background that the right-sided colon was the most difficult segment
to prep. What is the reason to compare the right colon prep with other segments? The comparison
among each segment preparation quality and 90%target did not add any value to the readers. I
suggest shortening the result of the study and all figure 4 (a-d) should be removed.
7. In supplementary table 3, the mean BMI of all cohorts was over 25 kg/m2. The authors should
demonstrate the percentage of overweight patients (BMI # 25 kg/m2) in table 3. This will enable
the reader to understand the overall characteristic of hard-to-cleanse patients.
8. The hard-to-cleanse patients in this study defined only male patients with BMI # 25 kg/m2.
However, the predictive factors for difficult preparation also included the elderly, in-patient
status for colonoscopy, patients with constipation, or patients with comorbidities. What were the
reasons for not including other important factors contributing to hard- or difficult-to-cleanse? If
so, the authors should replace hard-to-cleanse patients to overweight patients.
9. Figure 5a, 5b can be combined, and figure 5c and 5d can be combined. Or for minimizing
confusion, figure 5d can be omitted.
10. It seems that the discussion was the repeated writing of the result. Please provide a discussion
on the reasons for your findings. Why the right-sided colon was well cleaned with NER1006
than other regimens.
11. If the MORA and NOCT participants were almost identical, I suggest incorporating two
N2D NER1006 cohorts and analyzing them as a single cohort. This will reduce the difficulty
to read and follow this study.
Please review this paper.
user
Title: 1L NER1006 can improve rates of adequate and high-quality bowel cleansing in the right
colon: a post hoc analysis of two randomised clinical trials
Version: 0 Date: 26 Oct 2021
Reviewer's report:
This post hoc analysis from two previous studies (MORA, NOCT) included 1,307 patients,
aimed to evaluate the 4 following topics;
- Whether those three regimens; NER1006, 2LPEG, and OSS can attain an adequate cleansing
level in the right colon greater than 90% using the Harefield Cleansing Scale.
- Comparative adequate and high-quality cleansing levels were attained in the right colon with
NER1006 and comparators
- Comparative adequate-quality cleansing level attained by NER1006 in the right colon and all
other colon segments
- The cleansing impact of NER1006 in the right colon in patients who are at increased risk for
inadequate bowel preparation
The cleansing performance in this post hoc analysis was evaluated via recorded VDO by central
readers.
Although the topics in this study are interesting in themselves and deserve a constructive
discussion, I have a few comments as indicated below. I hope these comments will be helpful.
Comments
1. The title of the study can be confused the readers. The total volume of the preparation regimen
was 2 liters and the design of the retrospective study was not mentioned.
2. The mFAS2 population set used in this analysis did not represent the real-world situation as
some of the randomized patients did not take the study drug, for unknown reasons. And the main
limitation of participants in this study was selective using only patients who had been assessed
for Harefield Cleansing Scale in all segments.
3. The fasting time before colonoscopy in these cohorts was very short, only 1-2 hours. I think
this protocol was the most important contribution to the excellent preparation quality in the right
side colon and also the whole colon. This issue should be emphasized to the readers.
4. How many VDO readers that involved in the data collection. How was the agreement among
the readers? Were readers blinded for the bowel preparation regimens?
5. Figure 2a showed the percentage of adequate preparation in the right colon segment and the p-
value demonstrated the difference between each regimen and minimum standard recommended
by ESGE. I think it was not necessary to demonstrate.
6. Authors mentioned in the background that the right-sided colon was the most difficult segment
to prep. What is the reason to compare the right colon prep with other segments? The comparison
among each segment preparation quality and 90%target did not add any value to the readers. I
suggest shortening the result of the study and all figure 4 (a-d) should be removed.
7. In supplementary table 3, the mean BMI of all cohorts was over 25 kg/m2. The authors should
demonstrate the percentage of overweight patients (BMI # 25 kg/m2) in table 3. This will enable
the reader to understand the overall characteristic of hard-to-cleanse patients.
8. The hard-to-cleanse patients in this study defined only male patients with BMI # 25 kg/m2.
However, the predictive factors for difficult preparation also included the elderly, in-patient
status for colonoscopy, patients with constipation, or patients with comorbidities. What were the
reasons for not including other important factors contributing to hard- or difficult-to-cleanse? If
so, the authors should replace hard-to-cleanse patients to overweight patients.
9. Figure 5a, 5b can be combined, and figure 5c and 5d can be combined. Or for minimizing
confusion, figure 5d can be omitted.
10. It seems that the discussion was the repeated writing of the result. Please provide a discussion
on the reasons for your findings. Why the right-sided colon was well cleaned with NER1006
than other regimens.
11. If the MORA and NOCT participants were almost identical, I suggest incorporating two
N2D NER1006 cohorts and analyzing them as a single cohort. This will reduce the difficulty
to read and follow this study.
assistant